Diagnostic_and_Statistical 06

 

Hallucinogen-Related Disorders

Phencyclidine Use Disorder

Other Hallucinogen Use Disorder

Phencyclidine Intoxication

Other Hallucinogen Intoxication

Hallucinogen Persisting Perception Disorder

Other Phencyclidine-induced Disorders

Other Hallucinogen-induced Disorders

Unspecified Phencyclidine-Related Disorder

Unspecified Hallucinogen-Related Disorder

Phencyclidine Use Disorder

Diagnostic Criteria

A. A pattern of phencyclidine (or a pharmacologically similar substance) use leading to

clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. Phencyclidine is often taken in larger amounts or over a longer period than was intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control phencyclidine use.

3. A great deal of time is spent in activities necessary to obtain phencyclidine, use the

phencyclidine, or recover from its effects.

4. Craving, or a strong desire or urge to use phencyclidine.

5. Recurrent phencyclidine use resulting in a failure to fulfill major role obligations at

work, school, or home (e.g., repeated absences from work or poor work performance

related to phencyclidine use; phencyclidine-related absences, suspensions, or expulsions from school; neglect of children or household).

6. Continued phencyclidine use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the phencyclidine (e.g.,

arguments with a spouse about consequences of intoxication; physical fights).

7. Important social, occupational, or recreational activities are given up or reduced because of phencyclidine use.

8. Recurrent phencyclidine use in situations in which it is physically hazardous (e.g.,

driving an automobile or operating a machine when impaired by a phencyclidine).

9. Phencyclidine use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the phencyclidine.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the phencyclidine to achieve intoxication or desired effect.

b. A markedly diminished effect with continued use of the same amount of the

phencyclidine.

Note: Withdrawal symptoms and signs are not established for phencyclidines, and so this

criterion does not apply. (Withdrawal from phencyclidines has been reported in animals

but not documented in human users.)

Specify if:

In early remission: After full criteria for phencyclidine use disorder were previously

met, none of the criteria for phencyclidine use disorder have been met for at least

3 months but for less than 12 months (with the exception that Criterion A4, “Craving,

or a strong desire or urge to use the phencyclidine,” may be met).

In sustained remission: After full criteria for phencyclidine use disorder were previously met, none of the criteria for phencyclidine use disorder have been met at any time

during a period of 12 months or longer (with the exception that Criterion A4, “Craving,

or a strong desire or urge to use the phencyclidine,” may be met).

Specify if:

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to phencyclidines is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If a phencyclidine intoxication or another phencyclidine-induced mental disorder is also present, do not use the codes

below for phencyclidine use disorder. Instead, the comorbid phencyclidine use disorder is indicated in the 4th character of the phencyclidine-induced disorder code (see the coding note

for phencyclidine intoxication or a specific phencyclidine-induced mental disorder). For example, if there is comorbid phencyclidine-induced psychotic disorder, only the phencyclidineinduced psychotic disorder code is given, with the 4th character indicating whether the comorbid phencyclidine use disorder is mild, moderate, or severe: F16.159 for mild phencyclidine use disorder with phencyclidine-induced psychotic disorder or F16.259 for a moderate

or severe phencyclidine use disorder with phencyclidine-induced psychotic disorder.

Specify current severity:

305.90 (F I6.10) Mild: Presence of 2-3 symptoms.

304.60 (FI 6.20) Moderate: Presence of 4-5 symptoms.

304.60 (F16.20) Severe: Presence of 6 or more symptoms.

Specifiers

"In a controlled environment" applies as a further specifier of remission if the individual is

both in remission and in a controlled environment (i.e., in early remission in a controlled

environment or in sustained remission in a controlled environment). Examples of these

environments are closely supervised and substance-free jails, therapeutic communities,

and locked hospital units.

Diagnostic Features

The phencyclidines (or phencyclidine-like substances) include phencyclidine (e.g., PCP,

"angel dust") and less potent but similarly acting compounds such as ketamine, cyclohexamine, and dizocilpine. These substances were first developed as dissociative anesthetics

in the 1950s and became street drugs in the 1960s. They produce feelings of separation

from mind and body (hence "dissociative") in low doses, and at high doses, stupor and

coma can result. These substances are most commonly smoked or taken orally, but they

may also be snorted or injected. Although the primary psychoactive effects of PCP last for

a few hours, the total elimination rate of this drug from the body typically extends 8 days

or longer. The hallucinogenic effects in vulnerable individuals may last for weeks and may

precipitate a persistent psychotic episode resembling schizophrenia. Ketamine has been

observed to have utility in the treatment of major depressive disorder. Withdrawal symp­

toms have not been clearly established in humans, and therefore the withdraw^al criterion

is not included in the diagnosis of phencyclidine use disorder.

Associated Features Supporting Diagnosis

Phencyclidine may be detected in urine for up to 8 days or even longer at very high doses. In

addition to laboratory tests to detect its presence, characteristic symptoms resulting from

intoxication v^ith phencyclidine or related substances may aid in its diagnosis. Phencyclidine is likely to produce dissociative symptoms, analgesia, nystagmus, and hypertension,

with risk of hypotension and shock. Violent behavior can also occur with phencyclidine

use, as intoxicated persons may believe that they are being attacked. Residual symptoms

following use may resemble schizophrenia.

Prevalence

The prevalence of phencyclidine use disorder is unknown. Approximately 2.5% of the population reports having ever used phencyclidine. The proportion of users increases with

age, from 0.3% of 12- to 17-year-olds, to 1.3% of 18- to 25-year-olds, to 2.9% of those age 26

years and older reporting ever using phencyclidine. There appears to have been an increase among 12th graders in both ever used (to 2.3% from 1.8%) and past-year use (to 1.3%

from 1.0%) of phencyclidine. Past-year use of ketamine appears relatively stable among

12th graders (1.6%-1.7% over the past 3 years).

Risic and Prognostic Factors

There is little information about risk factors for phencyclidine use disorder. Among individuals admitted to substance abuse treatment, those for whom phencyclidine was the

primary substance were younger than those admitted for other substance use, had lower

educational levels, and were more likely to be located in the West and Northeast regions of

the United States, compared with other admissions.

Cuiture-Reiated Diagnostic issues

Ketamine use in youths ages 16-23 years has been reported to be more common among

whites (0.5%) than among other ethnic groups (range 0%-0.3%). Among individuals admitted to substance abuse treatment, those for whom phencyclidine was the primary substance were predominantly black (49%) or Hispanic (29%).

Gender-Reiated Diagnostic issues

Males make up about three-quarters of those with phencyclidine-related emergency room

visits.

Diagnostic iViaricers

Laboratory testing may be useful, as phencyclidine is present in the urine in intoxicated individuals up to 8 days after ingestion. The individual's history, along with certain physical

signs, such as nystagmus, analgesia and prominent hypertension, may aid in distinguishing the phencyclidine clinical picture from that of other hallucinogens.

Functional Consequences of Pliencyclidine Use Disorder

In individuals with phencyclidine use disorder, there may be physical evidence of injuries

from accidents, fights, and falls. Chronic use of phencyclidine may lead to deficits in memory, speech, and cognition that may last for months. Cardiovascular and neurological toxicities (e.g., seizures, dystonias, dyskinesias, catalepsy, hypothermia or hyperthermia)

may result from intoxication with phencyclidine. Other consequences include intracranial

hemorrhage, rhabdomyolysis, respiratory problems, and (occasionally) cardiac arrest.

Differential Diagnosis

\

Other substance use disorders. Distinguishing the effects of phencychdine from those

of other substances is important, since it may be a common additive to other substances

(e.g., cannabis, cocaine).

Schizophrenia and other mental disorders. Some of the effects of phencychdine and

related substance use may resemble symptoms of other psychiatric disorders, such as psychosis (schizophrenia), low mood (major depressive disorder), violent aggressive behaviors (conduct disorder, antisocial personality disorder). Discerning whether these

behaviors occurred before the intake of the drug is important in the differentiation of acute

drug effects from preexisting mental disorder. Phencyclidine-induced psychotic disorder

should be considered when there is impaired reality testing in individuals experiencing

disturbances in perception resulting from ingestion of phencyclidine.

Other Hallucinogen Use Disorder

Diagnostic Criteria

A. A problematic pattern of hallucinogen (other than phencyclidine) use leading to clinically significant impairment or distress, as manifested by at least two of the following,

occurring within a 12-month period:

1. The hallucinogen is often taken in larger amounts or over a longer period than was

intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control hallucinogen use.

3. A great deal of time is spent in activities necessary to obtain the hallucinogen, use

the hallucinogen, or recover from its effects.

4. Craving, or a strong desire or urge to use the hallucinogen.

5. Recurrent hallucinogen use resulting in a failure to fulfill major role obligations at

work, school, or home (e.g., repeated absences from work or poor work performance related to hallucinogen use; hallucinogen-related absences, suspensions,

or expulsions from school; neglect of children or household).

6. Continued hallucinogen use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the hallucinogen (e.g.,

arguments with a spouse about consequences of intoxication; physical fights).

7. Important social, occupational, or recreational activities are given up or reduced because of hallucinogen use.

8. Recurrent hallucinogen use in situations in which it is physically hazardous (e.g.,

driving an automobile or operating a machine when impaired by the hallucinogen).

9. Hallucinogen use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the hallucinogen.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the hallucinogen to achieve intoxication or desired effect.

b. A markedly diminished effect with continued use of the same amount of the hallucinogen.

Note: Withdrawal symptoms and signs are not established for hallucinogens, and so this

criterion does not apply.

Specify the particular hallucinogen.

Specify if:

In early remission: After full criteria for other hallucinogen use disorder were previously met, none of the criteria for other hallucinogen use disorder have been met for

at least 3 months but for less than 12 months (with the exception that Criterion A4,

“Craving, or a strong desire or urge to use the hallucinogen,” may be met).

In sustained remission: After full criteria for other hallucinogen use disorder were

previously met, none of the criteria for other hallucinogen use disorder have been met

at any time during a period of 12 months or longer (with the exception that Criterion A4,

“Craving, or a strong desire or urge to use the hallucinogen,” may be met).

Specify if:

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to hallucinogens is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If a hallucinogen intoxication

or another hallucinogen-induced mental disorder is also present, do not use the codes below

for hallucinogen use disorder. Instead, the comorbid hallucinogen use disorder is indicated in

the 4th character of the hallucinogen-induced disorder code (see the coding note for hallucinogen intoxication or specific hallucinogen-induced mental disorder). For example, if there is

comorbid hallucinogen-induced psychotic disorder and hallucinogen use disorder, only the

hallucinogen-induced psychotic disorder code is given, with the 4th character indicating whether the comorbid hallucinogen use disorder is mild, moderate, or severe: F16.159 for mild hallucinogen use disorder with hallucinogen-induced psychotic disorder or F16.259 for a

moderate or severe hallucinogen use disorder with hallucinogen-induced psychotic disorder.

Specify current severity:

305.30 (FI 6.10) IWild: Presence of 2-3 symptoms.

304.50 (F16.20) Moderate: Presence of 4-5 symptoms.

304.50 (F16.20) Severe: Presence of 6 or more symptoms.

Specifiers

"In a controlled environment" applies as a further specifier of remission if the individual is

both in remission and in a controlled environment (i.e., in early remission in a controlled

environment or in sustained remission in a controlled environment). Examples of these

environments are closely supervised and substance-free jails, therapeutic communities,

and locked hospital units.

Diagnostic Features

Hallucinogens comprise a diverse group of substances that, despite having different chemical structures and possibly involving different molecular mechanisms, produce similar

alterations of perception, mood, and cognition in users. Hallucinogens included are phenylalkylamines (e.g., mescaline, DOM [2,5-dimethoxy-4-methylamphetamine], and MDMA

[3,4-methylenedioxymethamphetamine; also called "ecstasy"]); the indoleamines, including psilocybin (i.e., psilocin) and dimethyltryptamine (DMT); and the ergolines, such as LSD

(lysergic acid diethylamide) and morning glory seeds. In addition, miscellaneous other

ethnobotanical compounds are classified as "hallucinogens," of which Salvia divinorum and

jimsonweed are two examples. Excluded from the hallucinogen group are cannabis and its

active compound, delta-9-tetrahydrocannabinol (THC) (see the section "Cannabis-Related

Disorders"). These substances can have hallucinogenic effects but are diagnosed separately

because of significant differences in their psychological and behavioral effects.

Hallucinogens are usually taken orally, although some forms are smoked (e.g., DMT,

salvia) or (rarely) taken intranasally or by injection (e.g., ecstasy). Duration of effects varies

across types of hallucinogens. Some of these substances (i.e., LSD, MDMA) have a long

half-life and extended duration such that users may spend hours to days using and/or recovering from the effects of these drugs. However, other hallucinogenic drugs (e.g., DMT,

salvia) are short acting. Tolerance to hallucinogens develops with repeated use and has

been reported to have both autonomic and psychological effects. Cross-tolerance exists between LSD and other hallucinogens (e.g., psilocybin, mescaline) but does not extend to

other drug categories such as amphetamines and cannabis.

MDMA/ecstasy as a hallucinogen may have distinctive effects attributable to both its hallucinogenic and its stimulant properties. Among heavy ecstasy users, continued use despite

physical or psychological problems, tolerance, hazardous use, and spending a great deal of

time obtaining the substance are the most commonly reported criteria—over 50% in adults

and over 30% in a younger sample, while legal problems related to substance use and persistent desire/inability to quit are rarely reported. As found for other substances, diagnostic criteria for other hallucinogen use disorder are arrayed along a single continuum of severity.

One of the generic criteria for substance use disorders, a clinically significant withdrawal syndrome, has not been consistently documented in humans, and therefore the diagnosis of hallucinogen withdrawal syndrome is not included in DSM-5. However, there

is evidence of withdrawal from MDMA, with endorsement of two or more withdrawal

symptoms observed in 59%-98% in selected samples of ecstasy users. Both psychological

and physical problems have been commonly reported as withdrawal problems.

Associated Features Supporting Diagnosis

The characteristic symptom features of some of the hallucinogens can aid in diagnosis if

urine or blood toxicology results are not available. For example, individuals who use LSD

tend to experience visual hallucinations that can be frightening. Individuals intoxicated

with hallucinogens may exhibit a temporary increase in suicidality.

Prevalence

Of all substance use disorders, other hallucinogen use disorder is one of the rarest. The

12-month prevalence is estimated to be 0.5% among 12- to 17-year-olds and 0.1% among

adults age 18 and older in the United States. Rates are higher in adult males (0.2%) compared

with females (0.1%), but the opposite is observed in adolescent samples ages 12-17, in which

the 12-month rate is slightly higher in females (0.6%) than in males (0.4%). Rates are highest in

individuals younger than 30 years, with the peak occurring in individuals ages 18-29 years

(0.6%) and decreasing to virtually 0.0% among individuals age 45 and older.

There are marked ethnic differences in 12-month prevalence of other hallucinogen use

disorder. Among youths ages 12-17 years, 12-month prevalence is higher among Native

Americans and Alaska Natives (1.2%) than among Hispanics (0.6%), whites (0.6%), African Americans (0.2%), and Asian Americans and Pacific Islanders (0.2%). Among adults,

12-month prevalence of other hallucinogen use disorder is similar for Native Americans

and Alaska Natives, whites, and Hispanics (all 0.2%) but somewhat lower for Asian Americans and Pacific Islanders (0.07%) and African Americans (0.03%). Past-year prevalence is

higher in clinical samples (e.g., 19% in adolescents in treatment). Among individuals currently using hallucinogens in the general population, 7.8% (adult) to 17% (adolescent) had

a problematic pattern of use that met criteria for past-year other hallucinogen use disorder.

Among select groups of individuals who use hallucinogens (e.g., recent heavy ecstasy

use), 73.5% of adults and 77% of adolescents have a problematic pattern of use that may

meet other hallucinogen use disorder criteria.

Development and Course

Unlike most substances where an early age at onset is associated with elevations in risk for

the corresponding use disorder, it is unclear whether there is an association of an early age

at onset with elevations in risk for other hallucinogen use disorder. However, patterns of

drug consumption have been found to differ by age at onset, with early-onset ecstasy users

more likely to be polydrug users than their later-onset counterparts. There may be a disproportionate influence of use of specific hallucinogens on risk of developing other hallucinogen use disorder, with use of ecstasy/MDMA increasing the risk of the disorder

relative to use of other hallucinogens.

Little is knovm regarding the course of other hallucinogen use disorder, but it is generally

thought to have low incidence, low persistence, and high rates of recovery. Adolescents are especially at risk for using these drugs, and it is estimated that 2.7% of youths ages 12-17 years

have used one or more of these drugs in the past 12 months, with 44% having used ecstasy/

MDMA. Other hallucinogen use disorder is a disorder observed primarily in individuals

younger than 30 years, with rates vanishingly rare among older adults.

Risk and Prognostic Factors

Temperamental. In adolescents but not consistently in adults, MDMA use is associated with

an elevated rate of other hallucinogen use disorder. Other substance use disorders, particularly alcohol, tobacco, and cannabis, and major depressive disorder are associated with elevated rates of other hallucinogen use disorder. Antisocial personality disorder may be

elevated among individuals who use more than two other drugs in addition to hallucinogens,

compared with their counterparts with less extensive use history. The influence of adult antisocial behaviors—^but not conduct disorder or antisocial personality disorder—on other hallucinogen use disorder may be stronger in females than in males. Use of specific hallucinogens

(e.g., salvia) is prominent among individuals ages 18-25 years with other risk-taking behaviors

and illegal activities. Cannabis use has also been implicated as a precursor to initiation of use of

hallucinogens (e.g., ecstasy), along with early use of alcohol and tobacco. Higher drug use by

peers and high sensation seeking have also been associated with elevated rates of ecstasy use.

MDMA/ecstasy use appears to signify a more severe group of hallucinogen users.

Genetic and physiological. Among male twins, total variance due to additive genetics

has been estimated to range from 26% to 79%, with inconsistent evidence for shared environmental influences.

Culture-Related Diagnostic issues

Historically, hallucinogens have been used as part of established religious practices, such

as the use of peyote in the Native American Church and in Mexico. Ritual use by indigenous populations of psilocybin obtained from certain types of mushrooms has occurred in

South America, Mexico, and some areas in the United States, or of ayahuasca in the Santo

Daime and Uniäo de Vegetal sects. Regular use of peyote as part of religious rituals is not

linked to neuropsychological or psychological deficits. For adults, no race or ethnicity differences for the full criteria or for any individual criterion are apparent at this time.

Gender-Related Diagnostic Issues

In adolescents, females may be less likely than males to endorse ''hazardous use," and female gender may be associated with increased odds of other hallucinogen use disorder.

Diagnostic Markers

Laboratory testing can be useful in distinguishing among the different hallucinogens.

However, because some agents (e.g., LSD) are so potent that as little as 75 micrograms can

produce severe reactions, typical toxicological examination will not always reveal which

substance has been used.

Functional Consequences of

Other Hallucinogen Use Disorder

There is evidence for long-term neuro toxic effects of MDMA/ecstasy use, including impairments in memory, psychological function, and neuroendocrine function; serotonin

system dysfunction; and sleep disturbance; as well as adverse effects on brain microvasculature, white matter maturation, and damage to axons. Use of MDMA/ecstasy may diminish functional connectivity among brain regions.

Differential Diagnosis

Other substance use disorders. The effects of hallucinogens must be distinguished from

those of other substances (e.g., amphetamines), especially because contamination of the

hallucinogens with other drugs is relatively common.

Schizophrenia. Schizophrenia also must be ruled out, as some affected individuals (e.g.,

individuals with schizophrenia who exhibit paranoia) may falsely attribute their symptoms to use of hallucinogens.

Other mental disorders or medical conditions. Other potential disorders or conditions

to consider include panic disorder, depressive and bipolar disorders, alcohol or sedative

withdrawal, hypoglycemia and other metabolic conditions, seizure disorder, stroke, ophthalmological disorder, and central nervous system tumors. Careful history of drug taking, collateral reports from family and friends (if possible), age, clinical history, physical

examination, and toxicology reports should be useful in arriving at the final diagnostic decision.

Comorbidity

Adolescents who use MDMA/ecstasy and other hallucinogens, as well as adults who have

recently used ecstasy, have a higher prevalence of other substance use disorders compared

with nonhallucinogen substance users. Individuals who use hallucinogens exhibit elevations of nonsubstance mental disorders (especially anxiety, depressive, and bipolar disorders), particularly with use of ecstasy and salvia. Rates of antisocial personality disorder (but

not conduct disorder) are significantly elevated among individuals with other hallucinogen

use disorder, as are rates of adult antisocial behavior. However, it is unclear whether the

mental illnesses may be precursors to rather than consequences of other hallucinogen use

disorder (see the section "Risk and Prognostic Factors" for this disorder). Both adults and

adolescents who use ecstasy are more likely than other drug users to be polydrug users and

to have other drug use disorders.

Phencyclidine Intoxication

Diagnostic Criteria

A. Recent use of phencyclidine (or a pharmacologically similar substance).

B. Clinically significant problematic behavioral changes (e.g., belligerence, assaultiveness, impulsiveness, unpredictability, psychomotor agitation, impaired judgment) that

developed during, or shortly after, phencyclidine use.

C. Within 1 hour, two (or more) of the following signs or symptoms:

Note: When the drug is smoked, “snorted,” or used intravenously, the onset may be

particularly rapid.

1. Vertical or horizontal nystagmus.

2. Hypertension or tachycardia.

3. Numbness or diminished responsiveness to pain.

4. Ataxia.

5. Dysarthria.

6. Muscle rigidity.

7. Seizures or coma.

8. Hyperacusis.

D. The signs or symptoms are not attributable to another medical condition and are not better

explained by another mental disorder, including Intoxication with another substance.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

there is a comorbid phencyclidine use disorder. If a mild phencyclidine use disorder is comorbid, the ICD-10-CM code is F16.129, and if a moderate or severe phencyclidine use

disorder is comorbid, the ICD-10-CM code is F16.229. If there is no comorbid phencyclidine use disorder, then the ICD-10-CM code is F16.929.

Note: In addition to the section "Functional Consequences of Phencyclidine Intoxication,"

see the corresponding section in phencyclidine use disorder.

Diagnostic Features

Phencyclidine intoxication reflects the clinically significant behavioral changes that occur

shortly after ingestion of this substance (or a pharmacologically similar substance). The

most common clinical presentations of phencyclidine intoxication include disorientation,

confusion without hallucinations, hallucinations or delusions, a catatonic-like syndrome,

and coma of varying severity. The intoxication typically lasts for several hours but, depending on the type of clinical presentation and whether other drugs besides phencyclidine were consumed, may last for several days or longer.

Prevalence

Use of phencyclidine or related substances may be taken as an estimate of the prevalence

of intoxication. Approximately 2.5% of the population reports having ever used phencyclidine. Among high school students, 2.3% of 12th graders report ever using phencyclidine, with 57% having used in the past 12 months. This represents an increase from prior

to 2011. Past-year use of ketamine, which is assessed separately from other substances, has

remained stable over time, with about 1.7% of 12th graders reporting use.

Diagnostic IVIarlcers

Laboratory testing may be useful, as phencyclidine is detectable in urine for up to 8 days

following use, although the levels are only weakly associated with an individual's clinical

presentation and may therefore not be useful for case management. Creatine phosphokinase and aspartate aminotransferase levels may be elevated.

Functional Consequences of Phencyclidine Intoxication

Phencyclidine intoxication produces extensive cardiovascular and neurological (e.g., seizures, dystonias, dyskinesias, catalepsy, hypothermia or hyperthermia) toxicity.

Differential Diagnosis

In particular, in the absence of intact reality testing (i.e., without insight into any perceptual abnormalities), an additional diagnosis of phencyclidine-induced psychotic disorder

should be considered.

Other substance intoxication. Phencyclidine intoxication should be differentiated from

intoxication due to other substances, including other hallucinogens; amphetamine, co­

caine, or other stimulants; and anticholinergics, as well as withdrawal from benzodiazepines. Nystagm\is and bizarre and violent behavior may distinguish intoxication due to

phencyclidine from that due to other substances. Toxicological tests may be useful in making this distinction, since phencyclidine is detectable in urine for up to 8 days after use.

However, there is a weak correlation between quantitative toxicology levels of phencyclidine and clinical presentation that diminishes the utility of the laboratory findings for patient management.

Other conditions. Other conditions to be considered include schizophrenia, depression,

withdrawal from other drugs (e.g., sedatives, alcohol), certain metabolic disorders like hypoglycemia and hyponatremia, central nervous system tumors, seizure disorders, sepsis,

neuroleptic malignant syndrome, and vascular insults.

Other Hallucinogen Intoxication

Diagnostic Criteria

A. Recent use of a hallucinogen (other than phencyclidine).

B. Clinically significant problematic behavioral or psychological changes (e.g., marked

anxiety or depression, ideas of reference, fear of “losing one’s mind,” paranoid ideation, impaired judgment) that developed during, or shortly after, hallucinogen use.

C. Perceptual changes occurring in a state of full wakefulness and alertness (e.g., subjective intensification of perceptions, depersonalization, derealization, illusions, hallucinations, synesthesias) that developed during, or shortly after, hallucinogen use.

D. Two (or more) of the following signs developing during, or shortly after, hallucinogen

use:

1. Pupillary dilation.

2. Tachycardia.

3. Sweating.

4. Palpitations.

5. Blurring of vision.

6. Tremors.

7. Incoordination.

E. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication with another substance.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

there is a comorbid hallucinogen use disorder. If a mild hallucinogen use disorder is comorbid, the ICD-10-CM code is FI 6.129, and if a moderate or severe hallucinogen use

disorder is comorbid, the ICD-10-CM code is F16.229. If there is no comorbid hallucinogen

use disorder, then the ICD-10-CM code is F16.929._________________________________

Note; For information on Associated Features Supporting Diagnosis and Culture-Related

Diagnostic Issues, see the corresponding sections in other hallucinogen use disorder.

Diagnostic Features

Other hallucinogen intoxication reflects the clinically significant behavioral or psychological changes that occur shortly after ingestion of a hallucinogen. Depending on the specific

hallucinogen, the intoxication may last only minutes (e.g., for salvia) or several hours or

longer (e.g., for LSD [lysergic acid diethylamide] or MDMA [3,4-methylenedioxymethamphetamine]).

Prevalence

The prevalence of other hallucinogen intoxication may be estimated by use of those substances. In the United States, 1.8% of individuals age 12 years or older report using hallucinogens in the past year. Use is more prevalent among younger individuals, with 3.1% of

12- to 17-year-olds and 7.1% of 18- to 25-year-olds using hallucinogens in the past year,

compared with only 0.7% of individuals age 26 years or older. Twelve-month prevalence

for hallucinogen use is more common in males (2.4%) than in females (1.2%), and even

more so among 18- to 25-year-olds (9.2% for males vs. 5.0% for females). In contrast,

among individuals ages 12-17 years, there are no gender differences (3.1% for both genders). These figures may be used as proxy estimates for gender-related differences in the

prevalence of other hallucinogen intoxication.

Suicide Risic

Other hallucinogen intoxication may lead to increased suicidality, although suicide is rare

among users of hallucinogens.

Functional Consequences of

Otiier Hallucinogen Intoxication

Other hallucinogen intoxication can have serious consequences. The perceptual disturbances and impaired judgment associated with other hallucinogen intoxication can result

in injuries or fatalities from automobile crashes, physical fights, or unintentional selfinjury (e.g., attempts to "fly" from high places). Environmental factors and the personality

and expectations of the individual using the hallucinogen may contribute to the nature of

and severity of hallucinogen intoxication. Continued use of hallucinogens, particularly

MDMA, has also been linked with neurotoxic effects.

Differential Diagnosis

Other substance intoxication. Other hallucinogen intoxication should be differentiated

from intoxication with amphetamines, cocaine, or other stimulants; anticholinergics; inhalants; and phencyclidine. Toxicological tests are useful in making this distinction, and

determining the route of administration may also be useful.

Other conditions. Other disorders and conditions to be considered include schizophrenia, depression, withdrawal from other drugs (e.g., sedatives, alcohol), certain metabolic

disorders (e.g., hypoglycemia), seizure disorders, tumors of the central nervous system,

and vascular insults.

Hallucinogen persisting perception disorder. Other hallucinogen intoxication is distinguished from hallucinogen persisting perception disorder because the symptoms in the

latter continue episodically or continuously for weeks (or longer) after the most recent intoxication.

Other hallucinogen-induced disorders. Other hallucinogen intoxication is distinguished

from the other hallucinogen-induced disorders (e.g., hallucinogen-induced anxiety disorder, with onset during intoxication) because the symptoms in these latter disorders predominate the clinical presentation and are severe enough to warrant independent clinical

attention.

Hallucinogen Persisting Perception Disorder

_____________ \____________________________________________________________

Diagnostic Criteria 292.89 (F16.983)

A. Following cessation of use of a hallucinogen, the reexperiencing of one or more of the

perceptual symptoms that were experienced while intoxicated with the hallucinogen

(e.g., geometric hallucinations, false perceptions of movement in the peripheral visual

fields, flashes of color, intensified colors, trails of images of moving objects, positive

afterimages, halos around objects, macropsia and micropsia).

B. The symptoms in Criterion A cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C. The symptoms are not attributable to another medical condition (e.g., anatomical lesions and infections of the brain, visual epilepsies) and are not better explained by another mental disorder (e.g., delirium, major neurocognitive disorder, schizophrenia) or

hypnopompic hallucinations.

Diagnostic Features

The hallmark of hallucinogen persisting perception disorder is the reexperiencing, when the

individual is sober, of the perceptual disturbances that were experienced while the individual was intoxicated with the hallucinogen (Criterion A). The symptoms may include any

perceptual perturbations, but visual disturbances tend to be predominant. Typical of the abnormal visual perceptions are geometric hallucinations, false perceptions of movement in

the peripheral visual fields, flashes of color, intensified colors, trails of images of moving objects (i.e., images left suspended in the path of a moving object as seen in stroboscopic photography), perceptions of entire objects, positive afterimages (i.e., a same-colored or

complementary-colored "shadow" of an object remaining after removal of the object), halos

around objects, or misperception of images as too large (macropsia) or too small (micropsia).

Duration of the visual disturbances may be episodic or nearly continuous and must cause

clinically significant distress or impairment in social, occupational, or other important areas

of functioning (Criterion B). The disturbances may last for weeks, months, or years. Other

explanations for the disturbances (e.g., brain lesions, preexisting psychosis, seizure disorders, migraine aura without headaches) must be ruled out (Criterion C).

Hallucinogen persisting perception disorder occurs primarily after LSD (lysergic acid

diethylamide) use, but not exclusively. There does not appear to be a strong correlation between hallucinogen persisting perception disorder and number of occasions of hallucinogen use, with some instances of hallucinogen persisting perception disorder occurring in

individuals with minimal exposure to hallucinogens. Some instances of hallucinogen persisting perception disorder may be triggered by use of other substances (e.g., cannabis or

alcohol) or in adaptation to dark environments.

Associated Features Supporting Diagnosis

Reality testing remains intact in individuals with hallucinogen persisting perception disorder (i.e., the individual is aware that the disturbance is linked to the effect of the drug).

If this is not the case, another disorder might better explain the abnormal perceptions.

Prevalence

Prevalence estimates of hallucinogen persisting perception disorder are unknown. Initial

prevalence estimates of the disorder among individuals who use hallucinogens is approximately 4.2%.

Development and Course

Little is known about the development of hallucinogen persisting perception disorder. Its

course, as suggested by its name, is persistent, lasting for weeks, months, or even years in

certain individuals.

Risk and Prognostic Factors

There is little evidence regarding risk factors for hallucinogen persisting perception disorder, although genetic factors have been suggested as a possible explanation underlying

the susceptibility to LSD effects in this condition.

Functional Consequences of

Haliucinogen Persisting Perception Disorder

Although hallucinogen persisting perception disorder remains a chronic condition in

some cases, many individuals with the disorder are able to suppress the disturbances and

continue to function normally.

Differential Diagnosis

Conditions to be ruled out include schizophrenia, other drug effects, neurodegenerative

disorders, stroke, brain tumors, infections, and head trauma. Neuroimaging results in hallucinogen persisting perception disorder cases are typically negative. As noted earlier, reality testing remains intact (i.e., the individual is aware that the disturbance is linked to the

effect of the drug); if this is not the case, another disorder (e.g., psychotic disorder, another

medical condition) might better explain the abnormal perceptions.

Comorbidity

Common comorbid mental disorders accompanying hallucinogen persisting perception

disorder are panic disorder, alcohol use disorder, and major depressive disorder.

Other Phencyclidine-Induced Disorders

Other phencyclidine-induced disorders are described in other chapters of the manual with

disorders with which they share phenomenology (see the substance/medication-induced

mental disorders in these chapters): phencyclidine-induced psychotic disorder ("Schizophrenia Spectrum and Other Psychotic Disorders"); phencyclidine-induced bipolar disorder ("Bipolar and Related Disorders"); phencyclidine-induced depressive disorder

("Depressive Disorders"); and phencyclidine-induced anxiety disorder ("Anxiety Disorders"). For phencyclidine-induced intoxication delirium, see the criteria and discussion of

delirium in the chapter "Neurocognitive Disorders." These phencyclidine-induced disorders are diagnosed instead of phencyclidine intoxication only when the symptoms are sufficiently severe to warrant independent clinical attention.

Other Hallucinogen-Induced Disorders

The following other hallucinogen-induced disorders are described in other chapters of the

manual with disorders with which they share phenomenology (see the substance/medication-induced mental disorders in these chapters): other hallucinogen-induced psychotic

disorder ("Schizophrenia Spectrum and Other Psychotic Disorders"); other hallucinogeninduced bipolar disorder ("Bipolar and Related Disorders"); other hallucinogen-induced

depressive disorder ("Depressive Disorders"); and other hallucinogen-induced anxiety

disorder ("Anxiety Disorders"). For other hallucinogen intoxication delirium, see the criteria and discussion of delirium in the chapter "Neurocognitive Disorders." These hallucinogen-induced disorders are diagnosed instead of other hallucinogen intoxication only

when the symptoms are sufficiently severe to warrant independent clinical attention.

Unspecified Phencyclidine-Related Disorder

292.9 (F16.99)

This category applies to presentations in which symptoms characteristic of a phencyclidine-related disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full

criteria for any specific phencyclidine-related disorder or any of the disorders in the substance-related and addictive disorders diagnostic class.

Unspecified Hallucinogen-Related Disorder

292.9 (F16.99)

This category applies to presentations in which symptoms characteristic of a hallucinogenrelated disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria

for any specific hallucinogen-related disorder or any of the disorders in the substancerelated and addictive disorders diagnostic class.

Inhalant-Related Disorders

Inhalant Use Disorder

Inhalant Intoxication

Other Inhalant-Induced Disorders

Unspecified Inhalant-Related Disorder

Inhalant Use Disorder

Diagnostic Criteria

A. A problematic pattern of use of a hydrocarbon-based inhalant substance leading to

clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. The inhalant substance is often taken in larger amounts or over a longer period than

was intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control use of the

inhalant substance.

3. A great deal of time is spent in activities necessary to obtain the inhalant substance,

use it, or recover from its effects.

4. Craving, or a strong desire or urge to use the inhalant substance.

5. Recurrent use of the inhalant substance resulting in a failure to fulfill major role obligations at work, school, or home.

6. Continued use of the inhalant substance despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of its use.

7. Important social, occupational, or recreational activities are given up or reduced because of use of the inhalant substance.

8. Recurrent use of the inhalant substance in situations in which it is physically hazardous.

9. Use of the inhalant substance is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been

caused or exacerbated by the substance.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the inhalant substance to achieve

intoxication or desired effect.

b. A markedly diminished effect with continued use of the same amount of the inhalant substance.

Specify the particular inhalant: When possible, the particular substance involved should

be named (e.g., “solvent use disorder'’).

Specify if:

in early remission: After full criteria for inhalant use disorder were previously met,

none of the criteria for inhalant use disorder have been met for at least 3 months but

for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use the inhalant substance,” may be met).

In sustained remission: After full criteria for inhalant use disorder were previously

met, none of the criteria for inhalant use disorder have been met at any time during a

period of 12 months or longer (with the exception that Criterion A4, “Craving, or a

strong desire or urge to use the inhalant substance,” may be met).

Specify if:

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to inhalant substances is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If an inhalant intoxication

or another inhalant-induced mental disorder is also present, do not use the codes below

for inhalant use disorder. Instead, the comorbid inhalant use disorder is indicated in the

4th character of the inhalant-induced disorder code (see the coding note for inhalant intoxication or a specific inhalant-induced mental disorder). For example, if there is comorbid

inhalant-induced depressive disorder and inhalant use disorder, only the inhalant-induced

depressive disorder code is given, with the 4th character indicating whether the comorbid

inhalant use disorder is mild, moderate, or severe: F18.14 for mild inhalant use disorder

with inhalant-induced depressive disorder or FI 8.24 for a moderate or severe inhalant use

disorder with inhalant-induced depressive disorder.

Specify current severity:

305.90 (F18.10) Mild: Presence of 2-3 symptoms.

304.60 (F18.20) lUloderate: Presence of 4-5 symptoms.

304.60 (FI 8.20) Severe: Presence of 6 or more symptoms.

Specifiers

This manual reà^gnizes volatile hydrocarbon use meeting the above diagnostic criteria as

inhalant use disorder. Volatile hydrocarbons are toxic gases from glues, fuels, paints, and

other volatile compounds. When possible, the particular substance involved should be

named (e.g., "toluene use disorder"). However, most compounds that are inhaled are a

mixture of several substances that can produce psychoactive effects, and it is often difficult

to ascertain the exact substance responsible for the disorder. Unless there is clear evidence

that a single, unmixed substance has been used, the general term inhalant should be used

in recording the diagnosis. Disorders arising from inhalation of nitrous oxide or of amyl-,

butyl-, or isobutylnitrite are considered as other (or unknown) substance use disorder.

"In a controlled environment" applies as a further specifier of remission if the individual is both in remission and in a controlled environment (i.e., in early remission in a controlled environment or in sustained remission in a controlled environment). Examples of

these environments are closely supervised and substance-free jails, therapeutic communities, and locked hospital units.

The severity of individuals' inhalant use disorder is assessed by the number of diagnostic criteria endorsed. Changing severity of individuals' inhalant use disorder across

time is reflected by reductions in the frequency (e.g., days used per month) and/or dose

(e.g., tubes of glue per day) used, as assessed by the individual's self-report, report of others, clinician's observations, and biological testing (when practical).

Diagnostic Features

Features of inhalant use disorder include repeated use of an inhalant substance despite the

individual's knowing that the substance is causing serious problems for the individual

(Criterion A9). Those problems are reflected in the diagnostic criteria.

Missing work or school or inability to perform t)^ical responsibilities at work or school

(Criterion A5), and continued use of the inhalant substance even though it causes arguments

with family or friends, fights, and other social or interpersonal problems (Criterion A6), may

be seen in inhalant use disorder. Limiting family contact, work or school obligations, or recreational activities (e.g., sports, games, hobbies) may also occur (Criterion A7). Use of inhalants when driving or operating dangerous equipment (Criterion A8) is also seen.

Tolerance (Criterion AlO) and mild withdrawal are each reported by about 10% of individuals who use inhalants, and a few individuals use inhalants to avoid withdrawal.

However, because the withdrawal symptoms are mild, this manual neither recognizes a

diagnosis of inhalant withdrawal nor counts withdrawal complaints as a diagnostic criterion for inhalant use disorder.

Associated Features Supporting Diagnosis

A diagnosis of inhalant use disorder is supported by recurring episodes of intoxication

with negative results in standard drug screens (which do not detect inhalants); possession,

or lingering odors, of inhalant substances; peri-oral or peri-nasal "glue-sniffer's rash"; association with other individuals known to use inhalants; membership in groups with prevalent irüialant use (e.g., some native or aboriginal communities, homeless children in street

gangs); easy access to certain inhalant substances; paraphernalia possession; presence of

the disorder's characteristic medical complications (e.g., brain white matter pathology,

rhabdomyolysis); and the presence of multiple substance use disorders. Inhalant use and

inhalant use disorder are associated with past suicide attempts, especially among adults

reporting previous episodes of low mood or anhedonia.

Prevaience

About 0.4% of Americans ages 12-17 years have a pattern of use that meets criteria for inhalant use disorder in the past 12 months. Among those youths, the prevalence is highest

in Native Americans and lowest in African Americans. Prevalence falls to about 0.1% among

Americans ages 18-29 years, and only 0.02% w^hen all Americans 18 years or older are considered, v^ith almost no females and a preponderance of European Americans. Of course,

in isolated subgroups, prevalence may differ considerably from these overall rates.

Development and Course

About 10% of 13-year-old American children report having used inhalants at least once;

that percentage remains stable through age 17 years. Among those 12- to 17-year-olds who

use inhalants, the more-used substances include glue, shoe polish, or toluene; gasoline or

lighter fluid; or spray paints.

Only 0.4% of 12- to 17-year-olds progress to inhalant use disorder; those youths tend to

exhibit multiple other problems. The declining prevalence of inhalant use disorder after

adolescence indicates that this disorder usually remits in early adulthood.

Volatile hydrocarbon use disorder is rare in prepubertal children, most common in adolescents and young adults, and uncommon in older persons. Calls to poison-control centers for ''intentional abuse" of inhalants peak with calls involving individuals at age 14 years.

Of adolescents who use inhalants, perhaps one-fifth develop inhalant use disorder; a few

die from inhalant-related accidents, or "sudden sniffing death". But the disorder apparently

remits in many individuals after adolescence. Prevalence declines dramatically among individuals in their 20s. Those with inhalant use disorder extending into adulthood often

have severe problems: substance use disorders, antisocial personality disorder, and suicidal ideation with attempts.

Risk and Prognostic Factors

Temperamental. Predictors of progression from nonuse of inhalants, to use, to inhalant

use disorder include comorbid non-inhalant substance use disorders and either conduct

disorder or antisocial personality disorder. Other predictors are earlier onset of inhalant

use and prior use of mental health services.

Environmental. Inhalant gases are widely and legally available, increasing the risk of misuse. Childhood maltreatment or trauma also is associated with youthful progression from

inhalant non-use to inhalant use disorder.

Genetic and physiological. Behavioral disinhihition is a highly heritable general propensity

to not constrain behavior in socially acceptable ways, to break social norms and rules, and to

take dangerous risks, pursuing rewards excessively despite dangers of adverse consequences.

Youths with strong behavioral disinhibition show risk factors for inhalant use disorder: earlyonset substance use disorder, multiple substance involvement, and early conduct problems.

Because behavioral disinhibition is under strong genetic influence, youths in families with

substance and antisocial problems are at elevated risk for inhalant use disorder.

Cuiture-Related Diagnostic issues

Certain native or aboriginal communities have experienced a high prevalence of inhalant

problems. Also, in some countries, groups of homeless children in street gangs have extensive inhalant use problems.

Gender-Reiated Diagnostic issues

Although the prevalence of inhalant use disorder is almost identical in adolescent males

and females, the disorder is very rare among adult females.

Diagnostic iVlaricers

Urine, breath, or saliva tests may be valuable for assessing concurrent use of non-inhalant

substances by individuals with inhalant use disorder. However, technical problems and

the considerable expense of analyses make frequent biological testing for inhalants themselves impractic^al.

Functional Consequences of Inhalant Use Disorder

Because of inherent toxicity, use of butane or propane is not infrequently fatal. Moreover,

any inhaled volatile hydrocarbons may produce "sudden sniffing death" from cardiac arrhythmia. Fatalities may occur even on the first inhalant exposure and are not thought to

be dose-related. Volatile hydrocarbon use impairs neurobehavioral function and causes

various neurological, gastrointestinal, cardiovascular, and pulmonary problems.

Long-term inhalant users are at increased risk for tuberculosis, HIV / AIDS, sexually

transmitted diseases, depression, anxiety, bronchitis, asthma, and sinusitis. Deaths may

occur from respiratory depression, arrhythmias, asphyxiation, aspiration of vomitus, or

accident and injury.

Differential Diagnosis

Inhalant exposure (unintentional) from industrial or other accidents. This designation

is used when findings suggest repeated or continuous inhalant exposure but the involved

individual and other informants deny any history of purposeful inhalant use.

Inhalant use (intentional), without meeting criteria for inhalant use disorder. Inhalant use

is common among adolescents, but for most of those individuals, the inhalant use does not

meet the diagnostic standard of two or more Criterion A items for inhalant use disorder in

the past year.

Inhalant intoxication, without meeting criteria for inhalant use disorder. Inhalant intoxication occurs frequently during inhalant use disorder but also may occur among individuals whose use does not meet criteria for inhalant use disorder, which requires at least two

of the 10 diagnostic criteria in the past year.

Inhalant-induced disorders (i.e., inhalant-induced psychotic disorder, depressive disorder, anxiety disorder, neurocognitive disorder, other inhalant-induced disorders)

without meeting criteria for inhalant use disorder. Criteria are met for a psychotic, depressive, anxiety, or major neurocognitive disorder, and there is evidence from history,

physical examination, or laboratory findings that the deficits are etiologically related to

the effects of inhalant substances. Yet, criteria for inhalant use disorder may not be met

(i.e., fewer than 2 of the 10 criteria were present).

Other substance use disorders, especially those involving sedating substances (e.g.,

alcohol, benzodiazepines, barbiturates). Inhalant use disorder commonly co-occurs

with other substance use disorders, and the symptoms of the disorders may be similar and

overlapping. To disentangle symptom patterns, it is helpful to inquire about which symptoms persisted during periods when some of the substances were not being used.

Other toxic, metabolic, traumatic, neoplastic, or infectious disorders impairing central or

peripheral nervous system function. Individuals with inhalant use disorder may present with symptoms of pernicious anemia, subacute combined degeneration of the spinal

cord, psychosis, major or minor cognitive disorder, brain atrophy, leukoencephalopathy,

and many other nervous system disorders. Of course, these disorders also may occur in

the absence of inhalant use disorder. A history of little or no inhalant use helps to exclude

inhalant use disorder as the source of these problems.

Disorders of other organ systems. Individuals with inhalant use disorder may present

with symptoms of hepatic or renal damage, rhabdomyolysis, methemoglobinemia, or symptoms of other gastrointestinal, cardiovascular, or pulmonary diseases. A history of little or no

inhalant use helps to exclude inhalant use disorder as the source of such medical problems.

Comorbidity

Individuals with inhalant use disorder receiving clinical care often have numerous other

substance use disorders. Inhalant use disorder commonly co-occurs with adolescent conduct disorder and adult antisocial personality disorder. Adult inhalant use and inhalant

use disorder also are strongly associated with suicidal ideation and suicide attempts.

Inhalant Intoxication

Diagnostic Criteria

A. Recent intended or unintended short-term, high-dose exposure to inhalant substances, including volatile hydrocarbons such as toluene or gasoline.

B. Clinically significant problematic behavioral or psychological changes (e.g., belligerence, assaultiveness, apathy, impaired judgment) that developed during, or shortly after, exposure to inhalants.

C. Two (or more) of the following signs or symptoms developing during, or shortly after,

inhalant use or exposure:

1. Dizziness.

2. Nystagmus.

3. Incoordination.

4. Slurred speech.

5. Unsteady gait.

6. Lethargy.

7. Depressed reflexes.

8. Psychomotor retardation.

9. Tremor.

10. Generalized muscle weakness.

11. Blurred vision or diplopia.

12. Stupor or coma.

13. Euphoria.

D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

there is a comorbid inhalant use disorder. If a mild inhalant use disorder is comorbid, the

ICD-10-CM code is F18.129, and if a moderate or severe inhalant use disorder is comorbid, the ICD-10-CM code is F18.229. If there is no comorbid inhalant use disorder, then

the ICD-10-CM code is FI 8.929.____________________________________________

Note: For information on Development and Course, Risk and Prognostic Factors, CultureRelated Diagnostic Issues, and Diagnostic Markers, see the corresponding sections in inhalant use disorder.

Diagnostic Features

Inhalant intoxication is an inhalant-related, clinically significant mental disorder that develops during, or immediately after, intended or unintended inhalation of a volatile hydrocarbon substance. Volatile hydrocarbons are toxic gases from glues, fuels, paints, and

other volatile compounds. When it is possible to do so, the particular substance involved

should be named (e.g., toluene intoxication). Among those who do, the intoxication clears

within a few minutes to a few hours after the exposure ends. Thus, inhalant intoxication

usually occurs in brief episodes that may recur.

Associated Features Supporting Diagnosis

Inhalant intoxicàtion may be indicated by evidence of possession, or lingering odors, of inhalant substances (e.g., glue, paint thinner, gasoline, butane lighters); apparent intoxication occurring in the age range with the highest prevalence of inhalant use (12-17 years);

and apparent intoxication with negative results from the standard drug screens that usually fail to identify inhalants.

Prevaience

The prevalence of actual episodes of inhalant intoxication in the general population is unknown, but it is probable that most inhalant users would at some time exhibit use that

would meet criteria for inhalant intoxication disorder. Therefore, the prevalence of inhalant use and the prevalence of inhalant intoxication disorder are likely similar. In 2009 and

2010, inhalant use in the past year was reported by 0.8% of all Americans older than 12 years;

the prevalence was highest in younger age groups (3.6% for individuals 12 to 17 years old,

and 1.7% for individuals 18 to 25 years old).

Gender-Reiated Diagnostic issues

Gender differences in the prevalence of inhalant intoxication in the general population are

unknown. However, if it is assumed that most inhalant users eventually experience inhalant intoxication, gender differences in the prevalence of inhalant users likely approximate

those in the proportions of males and females experiencing inhalant intoxication. Regarding gender differences in the prevalence of inhalant users in the United States, 1% of males

older than 12 years and 0.7% of females older than 12 years have used inhalants in the previous year, but in the younger age groups more females than males have used inhalants

(e.g., among 12- to 17-year-olds, 3.6% of males and 4.2% of females).

Functional Consequences of inhalant intoxication

Use of inhaled substances in a closed container, such as a plastic bag over the head, may

lead to unconsciousness, anoxia, and death. Separately, "sudden sniffing death," likely

from cardiac arrhythmia or arrest, may occur with various volatile inhalants. The enhanced toxicity of certain volatile inhalants, such as butane or propane, also causes fatalities. Although inhalant intoxication itself is of short duration, it may produce persisting

medical and neurological problems, especially if the intoxications are frequent.

Differential Diagnosis

Inhalant exposure, without meeting the criteria for inhalant intoxication disorder.

The individual intentionally or unintentionally inhaled substances, but the dose was insufficient for the diagnostic criteria for inhalant use disorder to be met.

Intoxication and other substance/medication-induced disorders from other substances, especially from sedating substances (e.g., alcohol, benzodiazepines, barbiturates). These disorders may have similar signs and symptoms, but the intoxication is

attributable to other intoxicants that may be identified via a toxicology screen. Differentiating the source of the intoxication may involve discerning evidence of inhalant exposure

as described for inhalant use disorder. A diagnosis of inhalant intoxication may be suggested by possession, or lingering odors, of inhalant substances (e.g., glue, paint thinner,

gasoline, butane lighters,); paraphernalia possession (e.g., rags or bags for concentrating

glue fumes); perioral or perinasal "glue-sniffer's rash"; reports from family or friends that

the intoxicated individual possesses or uses inhalants; apparent intoxication despite negahve results on standard drug screens (which usually fail to identify inhalants); apparent

intoxication occurring in that age range with the highest prevalence of inhalant use (12-17

years); association with others known to use inhalants; membership in certain small communities with prevalent inhalant use (e.g., some native or aboriginal communities, homeless street children and adolescents); or unusual access to certain inhalant substances.

Other inhalant-related disorders. Episodes of inhalant intoxication do occur during,

but are not identical with, other inhalant-related disorders. Those inhalant-related disorders

are recognized by their respective diagnostic criteria: inhalant use disorder, inhalantinduced neurocognitive disorder, inhalant-induced psychotic disorder, inhalant-induced

depressive disorder, inhalant-induced anxiety disorder, and other inhalant-induced disorders.

Other toxic, metabolic, traumatic, neoplastic, or infectious disorders that impair brain

function and cognition. Numerous neurological and other medical conditions may produce the clinically significant behavioral or psychological changes (e.g., belligerence, assaultiveness, apathy, impaired judgment) that also characterize inhalant intoxication.

Other Inhalant-Induced Disorders

The following inhalant-induced disorders are described in other chapters of the manual

with disorders with which they share phenomenology (see the substance/medicationinduced mental disorders in these chapters): inhalant-induced psychotic disorder ("Schizophrenia Spectrum and Other Psychotic Disorders"); inhalant-induced depressive disorder

("Depressive Disorders"); inhalant-induced anxiety disorder ("Anxiety Disorders"); and inhalant-induced major or mild neurocognitive disorder ("Neurocognitive Disorders"). For

inhalant intoxication delirium, see the criteria and discussion of delirium in the chapter

"Neurocognitive Disorders." These inhalant-induced disorders are diagnosed instead of inhalant intoxication only when symptoms are sufficiently severe to warrant independent

clinical attention.

Unspecified Inhalant-Related Disorder

292.9 (F18.99)

This category applies to presentations in wliich symptoms characteristic of an inhalantrelated disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria

for any specific inhalant-related disorder or any of the disorders in the substance-related

and addictive disorders diagnostic class.

Opioid-Related Disorders

Opioid Use Disorder

Opioid Intoxication

Opioid Withdrawai

Other Opioid-induced Disorders

Unspecified Opioid-Reiated Disorder

Opioid Use Disorder

_________________________________ \ —

Diagnostic Criteria

A. A problematic pattern of opioid use leading to clinically significant impairment or distress,

as manifested by at least two of the following, occurring within a 12-month period:

1. Opioids are often taken in larger amounts or over a longer period than was intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.

3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.

4. Craving, or a strong desire or urge to use opioids.

5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work,

school, or home.

6. Continued opioid use despite having persistent or recurrent social or interpersonal

problems caused or exacerbated by the effects of opioids.

7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.

8. Recurrent opioid use in situations in which it is physically hazardous.

9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by

the substance.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of opioids to achieve intoxication or desired effect.

b. A markedly diminished effect with continued use of the same amount of an opioid.

Note: This criterion is not considered to be met for those taking opioids solely under

appropriate medical supervision.

11. Withdrawal, as manifested by either of the following:

a. The characteristic opioid withdrawal syndrome (refer to Criteria A and B of the

criteria set for opioid withdrawal, pp. 547-548).

b. Opioids (or a closely related substance) are taken to relieve or avoid withdrawal

symptoms.

Note: This criterion is not considered to be met for those individuals taking opioids

solely under appropriate medical supervision.

Specify if:

In early remission: After full criteria for opioid use disorder were previously met, none

of the criteria for opioid use disorder have been met for at least 3 months but for less

than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or

urge to use opioids,” may be met).

In sustained remission: After full criteria for opioid use disorder were previously met,

none of the criteria for opioid use disorder have been met at any time during a period

of 12 months or longer (with the exception that Criterion A4, “Craving, or a strong desire or urge to use opioids,” may be met).

Specify if:

On maintenance therapy: This additional specifier is used if the individual is taking a

prescribed agonist medication such as methadone or buprenorphine and none of the

criteria for opioid use disorder have been met for that class of medication (except tolerance to, or withdrawal from, the agonist). This category also applies to those Individ­

uals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist

such as oral naltrexone or depot naltrexone.

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to opioids is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If an opioid intoxication,

opioid withdrawal, or another opioid-induced mental disorder is also present, do not use

the codes below for opioid use disorder. Instead, the comorbid opioid use disorder is indicated in the 4th character of the opioid-induced disorder code (see the coding note for opioid intoxication, opioid withdrawal, or a specific opioid-induced mental disorder). For

example, if there is comorbid opioid-induced depressive disorder and opioid use disorder,

only the opioid-induced depressive disorder code is given, with the 4th character indicating

whether the comorbid opioid use disorder is mild, moderate, or severe: F11.14 for mild opioid use disorder with opioid-induced depressive disorder or F11.24 for a moderate or severe opioid use disorder with opioid-induced depressive disorder.

Specify current severity:

305.50 (F11.10) Mild: Presence of 2 -3 symptoms.

304.00 (F11.20) Moderate: Presence of 4-5 symptoms.

304.00 (F11.20) Severe: Presence of 6 or more symptoms.

Specifiers

The "on maintenance therapy" specifier applies as a further specifier of remission if the individual is both in remission and receiving maintenance therapy. "In a controlled environment" applies as a further specifier of remission if the individual is both in renüssion and in

a controlled environment (i.e., in early remission in a controlled environment or in sustained

remission in a controlled environment). Examples of these environments are closely supervised and substance-free jails, therapeutic communities, and locked hospital units.

Changing severity across time in an individual is also reflected by reductions in the frequency (e.g., days of use per month) and/or dose (e.g., injections or number of pills) of an

opioid, as assessed by the individual's self-report, report of knowledgeable others, clinician's observations, and biological testing.

Diagnostic Features

Opioid use disorder includes signs and symptoms that reflect compulsive, prolonged selfadministration of opioid substances that are used for no legitimate medical purpose or, if

another medical condition is present that requires opioid treatment, that are used in doses

greatly in excess of the amount needed for that medical condition. (For example, an individual prescribed analgesic opioids for pain relief at adequate dosing will use significantly

more than prescribed and not only because of persistent pain.) Individuals with opioid use

disorder tend to develop such regular patterns of compulsive drug use that daily activities

are planned around obtaining and administering opioids. Opioids are usually purchased

on the illegal market but may also be obtained from physicians by falsifying or exaggerating general medical problems or by receiving simultaneous prescriptions from several

physicians. Health care professionals with opioid use disorder will often obtain opioids by

writing prescriptions for themselves or by diverting opioids that have been prescribed for

patients or from pharmacy supplies. Most individuals with opioid use disorder have

significant levels of tolerance and will experience withdrawal on abrupt discontinuation

of opioid substances. Individuals with opioid use disorder often develop conditioned

responses to drug-related stimuli (e.g., craving on seeing any heroin powder-like substance)—a phenomenon that occurs with most drugs that cause intense psychological

changes. These responses probably contribute to relapse, are difficult to extinguish, and typically persist long after detoxification is completed.

Associated Features Supporting Diagnosis

Opioid use disoMer can be associated with a history of drug-related crimes (e.g., possession or distribution of drugs, forgery, burglary, robbery, larceny, receiving stolen goods).

Among health care professionals and individuals who have ready access to controlled

substances, there is often a different pattern of illegal activities involving problems with

state licensing boards, professional staffs of hospitals, or other administrative agencies.

Marital difficulties (including divorce), unemployment, and irregular employment are often associated with opioid use disorder at all socioeconomic levels.

Prevaience

The 12-month prevalence of opioid use disorder is approximately 0.37% among adults age

18 years and older in the community population. This may be an underestimate because of

the large number of incarcerated individuals with opioid use disorders. Rates are higher in

males than in females (0.49% vs. 0.26%), with the male-to-female ratio typically being 1.5:1

for opioids other than heroin (i.e., available by prescription) and 3:1 for heroin. Female adolescents may have a higher likelihood of developing opioid use disorders. The prevalence decreases with age, with the prevalence highest (0.82%) among adults age 29 years or

younger, and decreasing to 0.09% among adults age 65 years and older. Among adults, the

prevalence of opioid use disorder is lower among African Americans at 0.18% and overrepresented among Native Americans at 1.25%. It is close to average among whites (0.38%),

Asian or Pacific Islanders (0.35%), and Hispanics (0.39%).

Among individuals in the United States ages 12-17 years, the overall 12-month prevalence of opioid use disorder in the community population is approximately 1.0%, but the

prevalence of heroin use disorder is less than 0.1%. By contrast, analgesic use disorder is

prevalent in about 1.0% of those ages 12-17 years, speaking to the importance of opioid analgesics as a group of substances with significant health consequences.

The 12-month prevalence of problem opioid use in European countries in the community population ages 15-64 years is between 0.1% and 0.8%. The average prevalence of

problem opioid use in the European Union and Norway is between 0.36% and 0.44%.

Development and Course

Opioid use disorder can begin at any age, but problems associated with opioid use are

most commonly first observed in the late teens or early 20s. Once opioid use disorder

develops, it usually continues over a period of many years, even though brief periods of

abstinence are frequent. In treated populations, relapse following abstinence is common.

Even though relapses do occur, and while some long-term mortality rates may be as high

as 2% per year, about 20%-30% of individuals with opioid use disorder achieve long-term

abstinence. An exception concerns that of military service personnel who became dependent on opioids in Vietnam; over 90% of this population who had been dependent on opioids during deployment in Vietnam achieved abstinence after they returned, but they

experienced increased rates of alcohol or amphetamine use disorder as well as increased

suicidality.

Increasing age is associated with a decrease in prevalence as a result of early mortality

and the remission of symptoms after age 40 years (i.e., "maturing out"). However, many

individuals continue have presentations that meet opioid use disorder criteria for decades.

Risl( and Prognostic Factors

Genetic and physiological. The risk for opiate use disorder can be related to individual,

family, peer, and social environmental factors, but within these domains, genetic factors

play a particularly important role both directly and indirectly. For instance, impulsivity

and novelty seeking are individual temperaments that relate to the propensity to develop

a substance use disorder but may themselves be genetically determined. Peer factors may

relate to genetic predisposition in terms of how an individual selects his or her environment.

Culture-Related Diagnostic Issues

Despite small variations regarding individual criterion items, opioid use disorder diagnostic criteria perform equally well across most race/ethnicity groups. Individuals from

ethnic minority populations living in economically deprived areas have been overrepresented among individuals with opioid use disorder. However, over time, opioid use

disorder is seen more often among white middle-class individuals, especially females,

suggesting that differences in use reflect the availability of opioid drugs and that other social factors may impact prevalence. Medical personnel who have ready access to opioids

may be at increased risk for opioid use disorder.

Diagnostic Markers

Routine urine toxicology test results are often positive for opioid drugs in individuals with

opioid use disorder. Urine test results remain positive for most opioids (e.g., heroin, morphine, codeine, oxycodone, propoxyphene) for 12-36 hours after administration. Fentanyl

is not detected by standard urine tests but can be identified by more specialized procedures for several days. Methadone, buprenorphine (or buprenorphine/naloxone combination), and LA AM (L-alpha-acetylmethadol) have to be specifically tested for and will not

cause a positive result on routine tests for opiates. They can be detected for several days up

to more than 1 week. Laboratory evidence of the presence of other substances (e.g., cocaine, marijuana, alcohol, amphetamines, benzodiazepines) is common. Screening test results for hepatitis A, B, and C virus are positive in as many as 80%-90% of injection opioid

users, either for hepatitis antigen (signifying active infection) or for hepatitis antibody (signifying past infection). HIV is prevalent in injection opioid users as well. Mildly elevated

liver function test results are common, either as a result of resolving hepatitis or from toxic

injury to the liver due to contaminants that have been mixed with the injected opioid. Subtle changes in cortisol secretion patterns and body temperature regulation have been observed for up to 6 months following opioid detoxification.

Suicide Risk

Similar to the risk generally observed for all substance use disorders, opioid use disorder

is associated with a heightened risk for suicide attempts and completed suicides. Particularly notable are both accidental and deliberate opioid overdoses. Some suicide risk factors

overlap with risk factors for an opioid use disorder. In addition, repeated opioid intoxication or withdrawal may be associated with severe depressions that, although temporary,

can be intense enough to lead to suicide attempts and completed suicides. Available data

suggest that nonfatal accidental opioid overdose (which is common) and attempted suicide are distinct clinically significant problems that should not be mistaken for each other.

Functional Consequences of Opioid Use Disorder

Opioid use is associated with a lack of mucous membrane secretions, causing dry mouth

and nose. Slowing of gastrointestinal activity and a decrease in gut motility can produce

severe constipation. Visual acuity may be impaired as a result of pupillary constriction

with acute administration. In individuals who inject opioids, sclerosed veins ("tracks")

and puncture marks on the lower portions of the upper extremities are common. Veins

sometimes become so severely sclerosed that peripheral edema develops, and individuals

switch to injecting in veins in the legs, neck, or groin. When these veins become unusable,

individuals often inject directly into their subcutaneous tissue ("skin-popping"), resulting

in cellulitis, abscesses, and circular-appearing scars from healed skin lesions. Tetanus and

Clostridium botulinum infections are relatively rare but extremely serious consequences of

injecting opioids, especially with contaminated needles. Infections may also occur in other

organs and include bacterial endocarditis, hepatitis, and HIV infection. Hepatitis C infections, for example, may occur in up to 90% of persons who inject opioids. In addition, the

prevalence of HIV infection can be high among individuals who inject drugs, a large proportion of whom are individuals with opioid use disorder. HIV infection rates have been

reported to be as high as 60% among heroin users with opioid use disorder in some areas

of the United States or the Russian Federation. However, the incidence may also be 10% or

less in other areas, especially those where access to clean injection material and paraphernalia is facilitated.

Tuberculosis is a particularly serious problem among individuals who use drugs intravenously, especially those who are dependent on heroin; infection is usually asymptomatic and evident only by the presence of a positive tuberculin skin test. However, many cases

of active tuberculosis have been found, especially among those who are infected with HIV.

These individuals often have a newly acquired infection but also are likely to experience

reactivation of a prior infection because of impaired immune function.

Individuals who sniff heroin or other opioids into the nose ("snorting") often develop

irritation of the nasal mucosa, sometimes accompanied by perforation of the nasal septum.

Difficulties in sexual functioning are cormnon. Males often experience erectile dysfunction

during intoxication or chronic use. Females commonly have disturbances of reproductive

function and irregular menses.

In relation to infections such as cellulitis, hepatitis, HIV infection, tuberculosis, and endocarditis, opioid use disorder is associated with a mortality rate as high as 1.5%-2% per

year. Death most often results from overdose, accidents, injuries, AIDS, or other general

medical complications. Accidents and injuries due to violence that is associated with buying or selling drugs are common. In some areas, violence accounts for more opioid-related

deaths than overdose or HIV infection. Physiological dependence on opioids may occur in

about half of the infants born to females with opioid use disorder; this can produce a severe withdrawal syndrome requiring medical treatment. Although low birth weight is

also seen in children of mothers with opioid use disorder, it is usually not marked and is

generally not associated with serious adverse consequences.

Differential Diagnosis

Opioid-induced mental disorders. Opioid-induced disorders occur frequently in individuals with opioid use disorder. Opioid-induced disorders may be characterized by symptoms

(e.g., depressed mood) that resemble primary mental disorders (e.g., persistent depressive disorder [dysthymia] vs. opioid-induced depressive disorder, with depressive features, with onset during intoxication). Opioids are less likely to produce symptoms of mental disturbance

than are most other drugs of abuse. Opioid intoxication and opioid withdrawal are distinguished from the other opioid-induced disorders (e.g., opioid-induced depressive disorder,

with onset during intoxication) because the symptoms in these latter disorders predominate

the clinical presentation and are severe enough to warrant independent clinical attention.

Other substance intoxication. Alcohol intoxication and sedative, hypnotic, or anxiolytic

intoxication can cause a clinical picture that resembles that for opioid intoxication. A diagnosis of alcohol or sedative, hypnotic, or anxiolytic intoxication can usually be made based

on the absence of pupillary constriction or the lack of a response to naloxone challenge. In

some cases, intoxication may be due both to opioids and to alcohol or other sedatives. In

these cases, the naloxone challenge will not reverse all of the sedative effects.

Other withdrawal disorders. The anxiety and restlessness associated with opioid withdrawal resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid

withdrawal is also accompanied by rhinorrhea, lacrimation, and pupillary dilation, which

are not seen in sedative-type withdrav^al. Dilated pupils are also seen in hallucinogen

intoxication and stimulant intoxication. However, other signs or symptoms of opioid

withdrav^al, such as nausea, vomiting, diarrhea, abdominal cramps, rhinorrhea, or lacrima tion, are not present.

Comorbidity

The most common medical conditions associated v/ith opioid use disorder are viral (e.g.,

HIV, hepatitis C virus) and bacterial infections, particularly among users of opioids by injection. These infections are less common in opioid use disorder v^ith prescription opioids.

Opioid use disorder is often associated w^ith other substance use disorders, especially those

involving tobacco, alcohol, cannabis, stimulants, and benzodiazepines, which are often

taken to reduce symptoms of opioid withdrawal or craving for opioids, or to enhance the effects of administered opioids. Individuals with opioid use disorder are at risk for the development of mild to moderate depression that meets symptomatic and duration criteria for

persistent depressive disorder (dysthymia) or, in some cases, for major depressive disorder.

These symptoms may represent an opioid-induced depressive disorder or an exacerbation

of a preexisting primary depressive disorder. Periods of depression are especially common

during chronic intoxication or in association with physical or psychosocial stressors that are

related to the opioid use disorder. Insomnia is common, especially during withdrawal. Antisocial personality disorder is much more common in individuals with opioid use disorder

than in the general population. Posttraumatic stress disorder is also seen with increased frequency. A history of conduct disorder in childhood or adolescence has been identified as a

significant risk factor for substance-related disorders, especially opioid use disorder.

Opioid Intoxication

Diagnostic Criteria

A. Recent use of an opioid.

B. Clinically significant problematic behavioral or psychological changes (e.g., initial euphoria followed by apathy, dysphoria, psychomotor agitation or retardation, impaired

judgment) that developed during, or shortly after, opioid use.

C. Pupillary constriction (or pupillary dilation due to anoxia from severe overdose) and

one (or more) of the following signs or symptoms developing during, or shortly after,

opioid use:

1. Drowsiness or coma.

2. Slurred speech.

3. Impairment in attention or memory.

D. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication with another substance.

Specify if:

With perceptual disturbances: This specifier may be noted in the rare instance in

which hallucinations with intact reality testing or auditory, visual, or tactile illusions occur in the absence of a delirium.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

or not there is a comorbid opioid use disorder and whether or not there are perceptual disturbances.

For opioid intoxication without perceptual disturbances: If a mild opioid use disorder is comorbid, the ICD-10-CM code is F11.129, and if a moderate or severe opioid

use disorder is comorbid, the ICD-10-CM code is F11.229. If there is no comorbid opioid use disorder, then the ICD-10-CM code is F11.929.

\

For opioid intoxication with perceptual disturbances: If a mild opioid use disorder

is comorbid, the ICD-10-CM code is F11.122, and if a moderate or severe opioid use

disorder is comorbid, the ICD-10-CM code is F11.222. If there is no comorbid opioid

use disorder, then the ICD-10-CM code is F11.922.

Diagnostic Features

The essential feature of opioid intoxication is the presence of clinically significant problematic behavioral or psychological changes (e.g., initial euphoria followed by apathy,

dysphoria, psychomotor agitation or retardation, impaired judgment) that develop during, or shortly after, opioid use (Criteria A and B). Intoxication is accompanied by pupillary constriction (unless there has been a severe overdose with consequent anoxia and

pupillary dilation) and one or more of the following signs: drowsiness (described as being "on the nod"), slurred speech, and impairment in attention or memory (Criterion C);

drowsiness may progress to coma. Individuals with opioid intoxication may demonstrate

inattention to the environment, even to the point of ignoring potentially harmful events.

The signs or symptoms must not be attributable to another medical condition and are not

better explained by another mental disorder (Criterion D).

Differential Diagnosis

Other substance intoxication. Alcohol intoxication and sedative-hypnotic intoxication

can cause a clinical picture that resembles opioid intoxication. A diagnosis of alcohol or

sedative-hypnotic intoxication can usually be made based on the absence of pupillary constriction or the lack of a response to a naloxone challenge. In some cases, intoxication may

be due both to opioids and to alcohol or other sedatives. In these cases, the naloxone challenge will not reverse all of the sedative effects.

Other opioid-related disorders. Opioid intoxication is distinguished from the other

opioid-induced disorders (e.g., opioid-induced depressive disorder, with onset during intoxication) because the symptoms in the latter disorders predominate in the clinical presentation and meet full criteria for the relevant disorder.

Opioid Withdrawal

Diagnostic Criteria 292.0 (F11.23)

A. Presence of either of the following;

1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,

several weeks or longer).

2. Administration of an opioid antagonist after a period of opioid use.

B. Three (or more) of the following developing within minutes to several days after Criterion A:

1. Dysphoric mood.

2. Nausea or vomiting.

3. Muscle aches.

4. Lacrimation or rhinorrhea.

5. Pupillary dilation, piloerection, or sweating.

6. Diarrhea.

7. Yawning.

8. Fever.

9. Insomnia.

C. The signs or symptoms in Criterion B cause clinically significant distress or impairment

in social, occupational, or other important areas of functioning.

D. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication or withdrawal from

another substance.

Coding note: The ICD-9-CM code is 292.0. The ICD-10-CM code for opioid withdrawal is

F11.23. Note that the ICD-10-CM code indicates the comorbid presence of a moderate or

severe opioid use disorder, reflecting the fact that opioid withdrawal can only occur in the

presence of a moderate or severe opioid use disorder. It is not permissible to code a comorbid mild opioid use disorder with opioid withdrawal.

Diagnostic Features

The essential feature of opioid withdrawal is the presence of a characteristic withdrawal

syndrome that develops after the cessation of (or reduction in) opioid use that has been

heavy and prolonged (Criterion Al). The withdrawal syndrome can also be precipitated

by administration of an opioid antagonist (e.g., naloxone or naltrexone) after a period of

opioid use (Criterion A2). This may also occur after administration of an opioid partial agonist such as buprenorphine to a person currently using a full opioid agonist.

Opioid withdrawal is characterized by a pattern of signs and symptoms that are opposite to the acute agonist effects. The first of these are subjective and consist of complaints of

anxiety, restlessness, and an "achy feeling" that is often located in the back and legs, along

with irritability and increased sensitivity to pain. Three or more of the following must be

present to make a diagnosis of opioid withdrawal: dysphoric mood; nausea or vomiting;

muscle aches; lacrimation or rhinorrhea; pupillary dilation, piloerection, or increased

sweating; diarrhea; yawning; fever; and insonmia (Criterion B). Piloerection and fever are

associated with more severe withdrawal and are not often seen in routine clinical practice

because individuals with opioid use disorder usually obtain substances before withdrawal becomes that far advanced. These symptoms of opioid withdrawal must cause

clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (Criterion D).

Meeting diagnostic criteria for opioid withdrawal alone is not sufficient for a diagnosis of

opioid use disorder, but concurrent symptoms of craving and drug-seeking behavior are

suggestive of comorbid opioid use disorder. ICD-IO-CM codes only allow a diagnosis of

opioid withdrawal in the presence of comorbid moderate to severe opioid use disorder.

The speed and severity of withdrawal associated with opioids depend on the half-life of

the opioid used. Most individuals who are physiologically dependent on short-acting drugs

such as heroin begin to have withdrawal symptoms within 6-12 hours after the last dose.

Symptoms may take 2-4 days to emerge in the case of longer-acting drugs such as methadone, LAAM (L-alpha-acetylmethadol), or buprenorphine. Acute withdrawal symptoms for

a short-acting opioid such as heroin usually peak within 1-3 days and gradually subside

over a period of 5-7 days. Less acute withdrawal symptoms can last for weeks to months.

These more chronic symptoms include anxiety, dysphoria, anhedonia, and insomnia.

Associated Features Supporting Diagnosis

Males with opioid withdrawal may experience piloerection, sweating, and spontaneous

ejaculations while awake. Opioid withdrawal is distinct from opioid use disorder and

does not necessarily occur in the presence of the drug-seeking behavior associated with

opioid use disorder. Opioid withdrawal may occur in any individual after cessation of repeated use of an opioid, whether in the setting of medical management of pain, during

opioid agonist therapy for opioid use disorder, in the context of private recreational use, or

following attempts to self-treat symptoms of mental disorders with opioids.

Prevaience

Among individuals from various clinical settings, opioid withdrawal occurred in 60% of

individuals who had used heroin at least once in the prior 12 months.

Deveiopment and Course

Opioid withdrawal is typical in the course of an opioid use disorder. It can be part of an escalating pattern in which an opioid is used to reduce withdrawal symptoms, in turn leading to more withdrawal at a later time. For persons with an established opioid use

disorder, withdrawal and attempts to relieve withdrawal are typical.

Differentiai Diagnosis

Other withdrawal disorders. The anxiety and restlessness associated with opioid withdrawal resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid withdrawal is also accompanied by rhinorrhea, lacrimation, and pupillary dilation, which are

not seen in sedative-type withdrawal.

Other substance intoxication. Dilated pupils are also seen in hallucinogen intoxication

and stimulant intoxication. However, other signs or symptoms of opioid withdrawal, such

as nausea, vomiting, diarrhea, abdominal cramps, rhinorrhea, and lacrimation, are not

present.

Other opioid-induced disorders. Opioid withdrawal is distinguished from the other

opioid-induced disorders (e.g., opioid-induced depressive disorder, with onset during

withdrawal) because the symptoms in these latter disorders are in excess of those usually

associated with opioid withdrawal and meet full criteria for the relevant disorder.

Other Opioid-Induced Disorders

The following opioid-induced disorders are described in other chapters of the manual with

disorders with which they share phenomenology (see the substance/medication-induced

mental disorders in these chapters): opioid-induced depressive disorder ("Depressive Disorders"); opioid-induced anxiety disorder ("Anxiety Disorders"); opioid-induced sleep

disorder ("Sleep-Wake Disorders"); and opioid-induced sexual dysfunction ("Sexual Dysfunctions"). For opioid intoxication delirium and opioid withdrawal delirium, see the criteria and discussion of delirium in the chapter "Neurocognitive Disorders." These opioidinduced disorders are diagnosed instead of opioid intoxication or opioid withdrawal only

when the symptoms are sufficiently severe to warrant independent clinical attention.

Unspecified Opioid-Related Disorder

292.9 (F11.99)

This category applies to presentations in which symptoms characteristic of an opioidrelated disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria

for any specific opioid-related disorder or any of the disorders in the substance-related and

addictive disorders diagnostic class.

Sedative-, Hypnotic-,

or Anxiolytic-Related Disorders

Sedative, Hypnotic, or Anxiolytic Use Disorder

Sedative, Hypnotic, or Anxiolytic Intoxication

Sedative, Hypnotic, or Anxiolytic Withdrawal

Other Sedative·, Hypnotic-, or Anxiolytic-Induced Disorders

Unspecified Sedative-, Hypnotic-, or Anxiolytic-Related Disorder

Sedative, Hypnotic, or Anxiolytic Use Disorder

Diagnostic Criteria

A. A problematic pattern of sedative, hypnotic, or anxiolytic use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring

within a 12-month period:

1. Sedatives, hypnotics, or anxiolytics are often taken in larger amounts or over a longer period than was intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control sedative,

hypnotic, or anxiolytic use.

3. A great deal of time is spent in activities necessary to obtain the sedative, hypnotic,

or anxiolytic; use the sedative, hypnotic, or anxiolytic; or recover from its effects.

4. Craving, or a strong desire or urge to use the sedative, hypnotic, or anxiolytic.

5. Recurrent sedative, hypnotic, or anxiolytic use resulting in a failure to fulfill major

role obligations at work, school, or home (e.g., repeated absences from work or

poor work performance related to sedative, hypnotic, or anxiolytic use; sedative-,

hypnotic-, or anxiolytic-related absences, suspensions, or expulsions from school;

neglect of children or household).

6. Continued sedative, hypnotic, or anxiolytic use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of

sedatives, hypnotics, or anxiolytics (e.g., arguments with a spouse about consequences of intoxication; physical fights).

7. Important social, occupational, or recreational activities are given up or reduced because of sedative, hypnotic, or anxiolytic use.

8. Recurrent sedative, hypnotic, or anxiolytic use in situations in which it is physically

hazardous (e.g., driving an automobile or operating a machine when impaired by

sedative, hypnotic, or anxiolytic use).

9. Sedative, hypnotic, or anxiolytic use is continued despite knowledge of having a

persistent or recurrent physical or psychological problem that is likely to have been

caused or exacerbated by the sedative, hypnotic, or anxiolytic.

10. Tolerance, as defined by either of the following;

a. A need for markedly increased amounts of the sedative, hypnotic, or anxiolytic

to achieve intoxication or desired effect.

b. A markedly diminished effect with continued use of the same amount of the sedative, hypnotic, or anxiolytic.

Note: This criterion is not considered to be met for individuals taking sedatives,

hypnotics, or anxiolytics under medical supervision.

11. Withdrawal, as manifested by either of the following:

a. The characteristic withdrawal syndrome for sedatives, hypnotics, or anxiolytics

(refer to Criteria A and B of the criteria set for sedative, hypnotic, or anxiolytic

withdrawal, pp. 557-558).

b. Sedatives, hypnotics, or anxiolytics (or a closely related substance, such as alcohol) are taken to relieve or avoid withdrawal symptoms.

Note: This criterion is not considered to be met for individuals taking sedatives,

hypnotics, or anxiolytics under medical supervision.

Specify if:

In early remission: After full criteria for sedative, hypnotic, or anxiolytic use disorder

were previously met, none of the criteria for sedative, hypnotic, or anxiolytic use disorder have been met for at least 3 months but for less than 12 months (with the exception

that Criterion A4, “Craving, or a strong desire or urge to use the sedative, hypnotic, or

anxiolytic,” may be met).

In sustained remission: After full criteria for sedative, hypnotic, or anxiolytic use disorder were previously met, none of the criteria for sedative, hypnotic, or anxiolytic use

disorder have been met at any time during a period of 12 months or longer (with the

exception that Criterion A4, “Craving, or a strong desire or urge to use the sedative,

hypnotic, or anxiolytic,” may be met).

Specify if:

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to sedatives, hypnotics, or anxiolytics is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If a sedative, hypnotic, or

anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; or another sedative-,

hypnotic-, or anxiolytic-induced mental disorder is also present, do not use the codes below for sedative, hypnotic, or anxiolytic use disorder. Instead the comorbid sedative, hypnotic, or anxiolytic use disorder is indicated in the 4th character of the sedative-, hypnotic-,

or anxiolytic-induced disorder (see the coding note for sedative, hypnotic, or anxiolytic intoxication; sedative, hypnotic, or anxiolytic withdrawal; or specific sedative-, hypnotic-, or

anxiolytic-induced mental disorder). For example, if there is comorbid sedative-, hypnotic-,

or anxiolytic-induced depressive disorder and sedative, hypnotic, or anxiolytic use disorder, only the sedative-, hypnotic-, or anxiolytic-induced depressive disorder code is given

with the 4th character indicating whether the comorbid sedative, hypnotic, or anxiolytic use

disorder is mild, moderate, or severe: F13.14 for mild sedative, hypnotic, or anxiolytk: use

disorder with sedative-, hypnotic-, or anxiolytic-induced depressive disorder or FI 3.24 for

a moderate or severe sedative, hypnotic, or anxiolytic use disorder with sedative-, hypnotic-,

or anxiolytic-induced depressive disorder.

Specify current severity:

305.40 (F13.10) Mild: Presence of 2-3 symptoms.

304.10 (F13.20) Moderate: Presence of 4 -5 symptoms.

304.10 (FI 3.20) Severe: Presence of 6 or more symptoms.

Specifiers

"In a controlled environment" applies as a further specifier of remission if the individual is

both in remission and in a controlled environment (i.e., in early remission in a controlled

environment or in sustained remission in a controlled environment). Examples of these

environments are closely supervised and substance-free jails, therapeutic communities,

and locked hospital units.

Diagnostic Features

Sedative, hypnotic, or anxiolytic substances include benzodiazepines, benzodiazepinelike drugs (e.g., zolpidem, zaleplon), carbamates (e.g., glutethimide, meprobamate),

barbiturates (e.g., secobarbital), and barbiturate-like hypnotics (e.g., glutethimide, methaqualone). This class of substances includes all prescription sleeping medications and

almost all prescription antianxiety medications. Nonbenzodiazepine antianxiety agents

(e.g., buspirone, gepirone) are not included in this class because they do not appear to be

associated with significant misuse.

Like alcohol, these agents are brain depressants and can produce similar substance/

medication-induced and substance use disorders. Sedative, hypnotic, or anxiolytic substances are available both by prescription and illegally. Some individuals who obtain these

substances by prescription will develop a sedative, hypnotic, or anxiolytic use disorder,

while others who misuse these substances or use them for intoxication will not develop a

use disorder. In particular, sedatives, hypnotics, or anxiolytics with rapid onset and/or

short to intermediate lengths of action may be taken for intoxication purposes, although

longer acting substances in this class may be taken for intoxication as well.

Craving (Criterion A4), either while using or during a period of abstinence, is a typical

feature of sedative, hypnotic, or anxiolytic use disorder. Misuse of substances from this

class may occur on its own or in conjunction with use of other substances. For example, individuals may use intoxicating doses of sedatives or benzodiazepines to "come down"

from cocaine or amphetamines or use high doses of benzodiazepines in combination with

methadone to "boost" its effects.

Repeated absences or poor work performance, school absences, suspensions or expulsions, and neglect of children or household (Criterion A5) may be related to sedative, hypnotic, or anxiolytic use disorder, as may the continued use of the substances despite

arguments with a spouse about consequences of intoxication or despite physical fights

(Criterion A6). Limiting contact with family or friends, avoiding work or school, or stopping participation in hobbies, sports, or games (Criterion A7) and recurrent sedative,

hypnotic, or anxiolytic use when driving an automobile or operating a machine when impaired by sedative, hypnotic, or anxiolytic use (Criterion A8) are also seen in sedative,

hypnotic, or anxiolytic use disorder.

Very significant levels of tolerance and withdrawal can develop to the sedative, hypnotic, or anxiolytic. There may be evidence of tolerance and withdrawal in the absence of

a diagnosis of a sedative, hypnotic, or anxiolytic use disorder in an individual who has

abruptly discontinued use of benzodiazepines that were taken for long periods of time at

prescribed and therapeutic doses. In these cases, an additional diagnosis of sedative, hypnotic, or anxiolytic use disorder is made only if other criteria are met. That is, sedative,

hypnotic, or anxiolytic medications may be prescribed for appropriate medical purposes,

and depending on the dose regimen, these drugs may then produce tolerance and with­

drawal. If these drugs are prescribed or recommended for appropriate medical purposes,

and if they are uöed as prescribed, the resulting tolerance or withdrawal does not meet the

criteria for diagnosing a substance use disorder. However, it is necessary to determine

whether the drugs were appropriately prescribed and used (e.g., falsifying medical symptoms to obtain the medication; using more medication than prescribed; obtaining the medication from several doctors without informing them of the others' involvement).

Given the unidimensional nature of the symptoms of sedative, hypnotic, or anxiolytic

use disorder, severity is based on the number of criteria endorsed.

Associated Features Supporting Diagnosis

Sedative, hypnotic, or anxiolytic use disorder is often associated with other substance use disorders (e.g., alcohol, cannabis, opioid, stimulant use disorders). Sedatives are often used to alleviate the unwanted effects of these other substances. With repeated use of the substance,

tolerance develops to the sedative effects, and a progressively higher dose is used. However,

tolerance to brain stem depressant effects develops much more slowly, and as the individual

takes more substance to achieve euphoria or other desired effects, there may be a sudden onset

of respiratory depression and hypotension, which may result in death. Intense or repeated

sedative, hypnotic, or anxiolytic intoxication may be associated with severe depression that,

although temporary, can lead to suicide attempt and completed suicide.

Prevalence

The 12-month prevalences of DSM-IV sedative, hypnotic, or anxiolytic use disorder are estimated to be 0.3% among 12- to 17-year-olds and 0.2% among adults age 18 years and

older. Rates of DSM-IV sedative, hypnotic, or anxiolytic use disorder are slightly greater

among adult males (0.3%) than among adult females, but for 12- to 17-year-olds, the rate

for females (0.4%) exceeds that for males (0.2%). The 12-month prevalence of DSM-IV

sedative, hypnotic, or anxiolytic use disorder decreases as a function of age and is greatest among 18- to 29-year-olds (0.5%) and lowest among individuals 65 years and older

(0.04%).

Twelve-month prevalence of sedative, hypnotic, or anxiolytic use disorder varies across

racial/ethnic subgroups of the U.S. population. For 12- to 17-year-olds, rates are greatest

among whites (0.3%) relative to African Americans (0.2%), Hispanics (0.2%), Native Americans (0.1%), and Asian Americans and Pacific Islanders (0.1%). Among adults, 12-month

prevalence is greatest among Native Americans and Alaska Natives (0.8%), with rates of

approximately 0.2% among African Americans, whites, and Hispanics and 0.1% among

Asian Americans and Pacific Islanders.

Development and Course

The usual course of sedative, hypnotic, or anxiolytic use disorder involves individuals in

their teens or 20s who escalate their occasional use of sedative, hypnotic, or anxiolytic

agents to the point at which they develop problems that meet criteria for a diagnosis. This

pattern may be especially likely among individuals who have other substance use disorders (e.g., alcohol, opioids, stimulants). An initial pattern of intermittent use socially (e.g.,

at parties) can lead to daily use and high levels of tolerance. Once this occurs, an increasing

level of interpersonal difficulties, as well as increasingly severe episodes of cognitive dysfunction and physiological withdrawal, can be expected.

The second and less frequently observed clinical course begins with an individual who

originally obtained the medication by prescription from a physician, usually for the treatment of anxiety, insomnia, or somatic complaints. As either tolerance or a need for higher

doses of the medication develops, there is a gradual increase in the dose and frequency of

self-administration. The individual is likely to continue to justify use on the basis of his or

her original symptoms of anxiety or insomnia, but substance-seeking behavior becomes

more prominent, and the individual may seek out multiple physicians to obtain sufficient

supplies of the medication. Tolerance can reach high levels, and withdrawal (including

seizures and withdrawal delirium) may occur.

As with many substance use disorders, sedative, hypnotic, or anxiolytic use disorder generally has an onset during adolescence or early adult life. There is an increased risk for misuse

and problems from many psychoactive substances as individuals age. In particular, cognitive

impairment increases as a side effect with age, and the metabolism of sedatives, hypnotics, or

anxiolytics decreases with age among older individuals. Both acute and chronic toxic effects

of these substances, especially effects on cognition, memory, and motor coordination, are

likely to increase with age as a consequence of pharmacodynamic and pharmacokinetic agerelated changes. Individuals with major neurocognitive disorder (dementia) are more likely

to develop intoxication and impaired physiological functioning at lower doses.

Deliberate intoxication to achieve a ''high" is most likely to be observed in teenagers

and individuals in their 20s. Problems associated with sedatives, hypnotics, or anxiolytics

are also seen in individuals in their 40s and older who escalate the dose of prescribed medications. In older individuals, intoxication can resemble a progressive dementia.

Risk and Prognostic Factors

Temperamental. Impulsivity and novelty seeking are individual temperaments that relate to the propensity to develop a substance use disorder but may themselves be genetically determined.

Environmental. Since sedatives, hypnotics, or anxiolytics are all pharmaceuticals, a key

risk factor relates to availability of the substances. In the United States, the historical patterns of sedative, hypnotic, or anxiolytic misuse relate to the broad prescribing patterns.

For instance, a marked decrease in prescription of barbiturates was associated with an increase in benzodiazepine prescribing. Peer factors may relate to genetic predisposition in

terms of how individuals select their environment. Other individuals at heightened risk

might include those with alcohol use disorder who may receive repeated prescriptions in

response to their complaints of alcohol-related anxiety or insomnia.

Genetic and physiological. As for other substance use disorders, the risk for sedative,

hypnotic, or anxiolytic use disorder can be related to individual, family, peer, social, and

environmental factors. Within these domains, genetic factors play a particularly important

role both directly and indirectly. Overall, across development, genetic factors seem to play

a larger role in the onset of sedative, hypnotic, or anxiolytic use disorder as individuals age

through puberty into adult life.

Course modifiers. Early onset of use is associated with greater likelihood for developing a sedative, hypnotic, or anxiolytic use disorder.

Culture-Related Diagnostic issues

There are marked variations in prescription patterns (and availability) of this class of substances in different countries, which may lead to variations in prevalence of sedative, hypnotic, or anxiolytic use disorders.

Gender-Related Diagnostic Issues

Females may be at higher risk than males for prescription drug misuse of sedative, hypnotic, or anxiolytic substances.

Diagnostic IViarkers

Almost all sedative, hypnotic, or anxiolytic substances can be identified through laboratory evaluations of urine or blood (the latter of which can quantify the amounts of these

agents in the body). Urine tests are likely to remain positive for up to approximately 1 week

after the use of long-acting substances, such as diazepam or flurazepam.

Functional Consequences of

Sedative, Hypnotic, or Anxioiytic Use Disorder

The social and interpersonal consequences of sedative, hypnotic, or anxiolytic use disorder

mimic those of alcohol in terms of the potential for disinhibited behavior. Accidents, interpersonal difficulties (such as arguments or fights), and interference with work or school performance are all common outcomes. Physical examination is likely to reveal evidence of a mild

decrease in most aspects of autonomic nervous system functioning, including a slower pulse,

a slightly decreased respiratory rate, and a slight drop in blood pressure (most likely to occur

with postural changes). At high doses, sedative, hypnotic, or anxiolytic substances can be lethal, particularly when mixed with alcohol, although the lethal dosage varies considerably

among the specific substances. Overdoses may be associated with a deterioration in vital signs

that signals an impending medical emergency (e.g., respiratory arrest from barbiturates).

There may be consequences of trauma (e.g., internal bleeding or a subdural hematoma) from

accidents that occur while intoxicated. Intravenous use of these substances can result in medical complications related to the use of contaminated needles (e.g., hepatitis and HIV).

Acute intoxication can result in accidental injuries and automobile accidents. For elderly

individuals, even short-term use of these sedating medications at prescribed doses can be associated with an increased risk for cognitive problems and falls. The disinhibiting effects of

these agents, Hke alcohol, may potentially contribute to overly aggressive behavior, with subsequent interpersonal and legal problems. Accidental or deliberate overdoses, similar to those

observed for alcohol use disorder or repeated alcohol intoxication, can occur. In contrast to

their wide margin of safety when used alone, benzodiazepines taken in combination with alcohol can be particularly dangerous, and accidental overdoses are reported commonly. Accidental overdoses have also been reported in individuals who deliberately misuse barbiturates

and other nonbenzodiazepine sedatives (e.g., methaqualone), but since these agents are much

less available than the benzodiazepines, the frequency of overdosing is low in most settings.

Differential Diagnosis

Other mental disorders or medical conditions. Individuals with sedative-, hypnotic-,

or anxiolytic-induced disorders may present with symptoms (e.g., anxiety) that resemble

primary mental disorders (e.g., generalized anxiety disorder vs. sedative-, hypnotic-, or

anxiolytic-induced anxiety disorder, with onset during withdrawal). The slurred speech,

incoordination, and other associated features characteristic of sedative, hypnotic, or anxiolytic intoxication could be the result of another medical condition (e.g., multiple sclerosis) or of a prior head trauma (e.g., a subdural hematoma).

Alcohol use disorder. Sedative, hypnotic, or anxiolytic use disorder must be differentiated from alcohol use disorder.

Clinically appropriate use of sedative, hypnotic, or anxiolytic medications. Individuals

may continue to take benzodiazepine medication according to a physician's direction for a

legitimate medical indication over extended periods of time. Even if physiological signs of

tolerance or withdrawal are manifested, many of these individuals do not develop symptoms that meet the criteria for sedative, hypnotic, or anxiolytic use disorder because they

are not preoccupied with obtaining the substance and its use does not interfere with their

performance of usual social or occupational roles.

Comorbidity

Nonmedical use of sedative, hypnotic, or anxiolytic agents is associated with alcohol use

disorder, tobacco use disorder, and, generally, illicit drug use. There may also be an over­

lap between sedative, hypnotic, or anxiolytic use disorder and antisocial personality disorder; depressive, bipolar, and anxiety disorders; and other substance use disorders, such

as alcohol use disorder and illicit drug use disorders. Antisocial behavior and antisocial

personality disorder are especially associated v^ith sedative, hypnotic, or anxiolytic use

disorder w^hen the substances are obtained illegally.

Sedative, Hypnotic, or Anxiolytic Intoxication

Diagnostic Criteria

A. Recent use of a sedative, hypnotic, or anxiolytic.

B. Clinically significant maladaptive behavioral or psychological changes (e.g., inappropriate sexual or aggressive behavior, mood lability, impaired judgment) that developed

during, or shortly after, sedative, hypnotic, or anxiolytic use.

C. One (or more) of the following signs or symptoms developing during, or shortly after,

sedative, hypnotic, or anxiolytic use:

1. Slurred speech.

2. Incoordination.

3. Unsteady gait.

4. Nystagmus.

5. Impairment in cognition (e.g., attention, memory).

6. Stupor or coma.

D. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication with another substance.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

there is a comorbid sedative, hypnotic, or anxiolytic use disorder. If a mild sedative, hypnotic, or anxiolytic use disorder is comorbid, the ICD-10-CM code is F13.129, and if a moderate or severe sedative, hypnotic, or anxiolytic use disorder is comorbid, the ICD-10-CM

code is FI 3.229. If there is no comorbid sedative, hypnotic, or anxiolytic use disorder, then

the ICD-10-CM code is FI 3.929.__________________________________________________

Note: For information on Development and Course; Risk and Prognostic Factors; CultureRelated Diagnostic Issues; Diagnostic Markers; Functional Consequences of Sedative,

Hypnotic, or Anxiolytic Intoxication; and Comorbidity, see the corresponding sections in

sedative, hypnotic, or anxiolytic use disorder.

Diagnostic Features

The essential feature of sedative, hypnotic, or anxiolytic intoxication is the presence of clinically significant maladaptive behavioral or psychological changes (e.g., inappropriate sexual

or aggressive behavior, mood lability, impaired judgment, impaired social or occupational

functioning) that develop during, or shortly after, use of a sedative, hypnotic, or anxiolytic

(Criteria A and B). As with other brain depressants, such as alcohol, these behaviors may be accompanied by slurred speech, incoordination (at levels that can interfere with driving abilities

and with performing usual activities to the point of causing falls or automobile accidents), an

unsteady gait, nystagmus, impairment in cognition (e.g., attentional or memory problems),

and stupor or coma (Criterion C). Memory impairment is a prominent feature of sedative, hypnotic, or anxiolytic intoxication and is most often characterized by an anterograde amnesia tiiat

resembles "alcoholic blackouts," which can be disturbing to the individual. The symptoms

must not be attributable to another medical condition and are not better explained by another

mental disorder (Criterion D). Intoxication may occur in individuals who are receiving these

substances by prescription, are borrov^ing the medication from friends or relatives, or are deliberately taking the substance to achieve intoxication.

Associated Features Supporting Diagnosis

Associated features include taking more medication than prescribed, taking multiple different medications, or mixing sedative, hypnotic, or anxiolytic agents with alcohol, which

can markedly increase the effects of these agents.

Prevaience

The prevalence of sedative, hypnotic, or anxiolytic intoxication in the general population

is unclear. However, it is probable that most nonmedical users of sedatives, hypnotics, or

anxiolytics would at some time have signs or symptoms that meet criteria for sedative,

hypnotic, or anxiolytic intoxication; if so, then the prevalence of nonmedical sedative,

hypnotic, or anxiolytic use in the general population may be similar to the prevalence of

sedative, hypnotic, or anxiolytic intoxication. For example, tranquilizers are used nonmedically by 2.2% of Americans older than 12 years.

Differentiai Diagnosis

Alcohol use disorders. Since the clinical presentations may be identical, distinguishing sedative, hypnotic, or anxiolytic intoxication from alcohol use disorders requires evidence for recent ingestion of sedative, hypnotic, or anxiolytic medications by self-report, informant report,

or toxicological testing. Many individuals who misuse sedatives, hypnotics, or anxiolytics may

also misuse alcohol and other substances, and so multiple intoxication diagnoses are possible.

Alcohol intoxication. Alcohol intoxication may be distinguished from sedative, hypnotic,

or anxiolytic intoxication by the smell of alcohol on the breath. Otherwise, the features of

the two disorders may be similar.

Other sedative-, hypnotic-, or anxiolytic-induced disorders. Sedative, hypnotic, or anxiolytic intoxication is distinguished from the other sedative-, hypnotic-, or anxiolyticinduced disorders (e.g., sedative-, hypnotic-, or anxiolytic-induced anxiety disorder, with

onset during withdrawal) because the symptoms in the latter disorders predominate in

the clinical presentation and are severe enough to warrant clinical attention.

Neurocognitive disorders. In situations of cognitive impairment, traumatic brain injury, and delirium from other causes, sedatives, hypnotics, or anxiolytics may be intoxicating at quite low dosages. The differential diagnosis in these complex settings is based

on the predominant syndrome. An additional diagnosis of sedative, hypnotic, or anxiolytic intoxication may be appropriate even if the substance has been ingested at a low dosage in the setting of these other (or similar) co-occurring conditions.

Sedative, Hypnotic, or Anxiolytic Withdrawal

Diagnostic Criteria

A. Cessation of (or reduction in) sedative, liypnotic, or anxiolytic use that has been prolonged.

B. Two (or more) of the following, developing within several hours to a few days after the cessation of (or reduction in) sedative, hypnotic, or anxiolytic use described in Criterion A:

1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 bpm).

2. Hand tremor.

3. Insomnia.

4. Nausea or vomiting.

5. Transient visual, tactile, or auditory hallucinations or illusions.

6. Psychomotor agitation.

7. Anxiety.

8. Grand mal seizures.

C. The signs or symptoms in Criterion B cause clinically significant distress or impairment

in social, occupational, or other important areas of functioning.

D. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication or withdrawal from

another substance.

Specify if:

With perceptual disturbances: This specifier may be noted when hallucinations with intact reality testing or auditory, visual, or tactile illusions occur in the absence of a delirium.

Coding note: The ICD-9-CM code is 292.0. The ICD-10-CM code for sedative, hypnotic,

or anxiolytic withdrawal depends on whether or not there is a comorbid moderate or severe sedative, hypnotic, or anxiolytic use disorder and whether or not there are perceptual

disturbances. For sedative, hypnotic, or anxiolytic withdrawal without perceptual disturbances, the ICD-10-CM code is F13.239. For sedative, hypnotic, or anxiolytic withdrawal

with perceptual disturbances, the ICD-10-CM code is F13.232. Note that the ICD-10-CM

codes indicate the comorbid presence of a moderate or severe sedative, hypnotic, or anxiolytic use disorder, reflecting the fact that sedative, hypnotic, or anxiolytic withdrawal can

only occur in the presence of a moderate or severe sedative, hypnotic, or anxiolytic use

disorder. It is not permissible to code a comorbid mild sedative, hypnotic, or anxiolytic use

disorder with sedative, hypnotic, or anxiolytic withdrawal.

Note: For information on Development and Course; Risk and Prognostic Factors; CultureRelated Diagnostic Issues; Functional Consequences of Sedative, Hypnotic, or Anxiolytic

Withdrawal; and Comorbidity, see the corresponding sections in sedative, hypnotic, or

anxiolytic use disorder.

Diagnostic Features

The essential feature of sedative, hypnotic, or anxiolytic withdrawal is the presence of a characteristic syndrome that develops after a marked decrease in or cessation of intake after several

weeks or more of regular use (Criteria A and B). This withdrawal syndrome is characterized by

two or more symptoms (similar to alcohol withdrawal) that include autonomic hyperactivity

(e.g., increases in heart rate, respiratory rate, blood pressure, or body temperature, along with

sweating); a tremor of the hands; insomnia; nausea, sometimes accompanied by vomiting;

anxiety; and psychomotor agitation. A grand mal seizure may occur in perhaps as many as

20%-30% of individuals undergoing untreated withdrawal from these substances. In severe

withdrawal, visual, tactile, or auditory hallucinations or illusions can occur but are usually in

the context of a delirium. If the individual's reality testing is intact (i.e., he or she knows the

substance is causing the hallucinations) and the illusions occur in a clear sensorium, the specifier 'Vith perceptual disturbances" can be noted. When hallucinations occur in the absence of

intact reality testing, a diagnosis of substance/medication-induced psychotic disorder should

be considered. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be

attributable to another medical condition and are not better explained by another mental disorder (e.g., alcohol withdrawal or generalized anxiety disorder) (Criterion D). Relief of withdrawal symptoms with administration of any sedative-hypnotic agent would support a

diagnosis of sedative, hypnotic, or anxiolytic withdrawal.

Associated Features Supporting Diagnosis

The timing and severity of the withdrawal syndrome will differ depending on the specific

substance and its pharmacokinetics and pharmacodynamics. For example, withdrawal

from shorter-acting substances that are rapidly absorbed and that have no active metabolites (e.g., triazolam) can begin within hours after the substance is stopped; withdrawal

from substances with long-acting metabolites (e.g., diazepam) may not begin for 1-2 days

or longer. The withdrawal syndrome produced by substances in this class may be characterized by the development of a delirium that can be life-threatening. There may be evidence of tolerance and withdrawal in the absence of a diagnosis of a substance use

disorder in an individual who has abruptly discontinued benzodiazepines that were taken

for long periods of time at prescribed and therapeutic doses. However, ICD-IO-CM codes

only allow a diagnosis of sedative, hypnotic, or anxiolytic withdrawal in the presence of

comorbid moderate to severe sedative, hypnotic, or anxiolytic use disorder.

The time course of the withdrawal syndrome is generally predicted by the half-life of

the substance. Medications whose actions typically last about 10 hours or less (e.g., lorazepam, oxazepam, temazepam) produce withdrawal symptoms within 6-8 hours of decreasing blood levels that peak in intensity on the second day and improve markedly by

the fourth or fifth day. For substances with longer half-lives (e.g., diazepam), symptoms

may not develop for more than 1 week, peak in intensity during the second week, and decrease markedly during the third or fourth week. There may be additional longer-term

symptoms at a much lower level of intensity that persist for several months.

The longer the substance has been taken and the higher the dosages used, the more likely

it is that there will be severe withdrawal. However, withdrawal has been reported with as little

as 15 mg of diazepam (or its equivalent in other benzodiazepines) when taken daily for several

months. Doses of approximately 40 mg of diazepam (or its equivalent) daily are more likely to

produce clinically relevant withdrawal symptoms, and even higher doses (e.g., 100 mg of diazepam) are more likely to be followed by withdrawal seizures or delirium. Sedative, hypnotic, or anxiolytic withdrawal delirium is characterized by disturbances in consciousness and

cognition, with visual, tactile, or auditory hallucinations. When present, sedative, hypnotic, or

anxiolytic withdrawal delirium should be diagnosed instead of withdrawal.

Prevalence

The prevalence of sedative, hypnotic, or anxiolytic withdrawal is unclear.

Diagnostic iVlarkers

Seizures and autonomic instability in the setting of a history of prolonged exposure to sedative, hypnotic, or anxiolytic medications suggest a high likelihood of sedative, hypnotic,

or anxiolytic withdrawal.

Differential Diagnosis

Other medical disorders. The symptoms of sedative, hypnotic, or anxiolytic withdrawal may be mimicked by other medical conditions (e.g., hypoglycemia, diabetic ketoacidosis). If seizures are a feature of the sedative, hypnotic, or anxiolytic withdrawal, the

differential diagnosis includes the various causes of seizures (e.g., infections, head injury,

poisonings).

Essential tremor. Essential tremor, a disorder that frequently runs in families, may

erroneously suggest the tremulousness associated with sedative, hypnotic, or anxiolytic

withdrawal.

Alcohol withdrawal. Alcohol withdrawal produces a syndrome very similar to that of

sedative, hypnotic, or anxiolytic withdrawal.

Other sedative-, hypnotic-, or anxiolytic-induced disorders. Sedative, hypnotic, or anxiolytic withdrawal is distinguished from the other sedative-, hypnotic-, or anxiolyticinduced disorders (e.g., sedative-, hypnotic-, or anxiolytic-induced anxiety disorder, with

onset during withdrawal) because the symptoms in the latter disorders predominate in

the clinical presentation and are severe enough to warrant clinical attention.

Anxiety disorders. Recurrence or worsening of an underlying anxiety disorder produces a syndrome similar to sedative, hypnotic, or anxiolytic withdrawal. Withdrawal

would be suspected with an abrupt reduction in the dosage of a sedative, hypnohc, or anxiolytic medication. When a taper is under way, distinguishing the withdrawal syndrome

from the underlying anxiety disorder can be difficult. As with alcohol, lingering withdrawal symptoms (e.g., anxiety, moodiness, and trouble sleeping) can be mistaken for

non-substance/medication-induced anxiety or depressive disorders (e.g., generalized

anxiety disorder).

Other Sedative-, Hypnotic-,

or Anxiolytic-Induced Disorders

The following sedative-, hypnotic-, or anxiolytic-induced disorders are described in other

chapters of the manual with disorders with which they share phenomenology (see the substance/medication-induced mental disorders in these chapters): sedative-, hypnotic-, or

anxiolytic-induced psychotic disorder (''Schizophrenia Spectrum and Other Psychotic

Disorders"); sedative-, hypnotic-, or anxiolytic-induced bipolar disorder ("Bipolar and Related Disorders"); sedative-, hypnotic-, or anxiolytic-induced depressive disorder ("Depressive Disorders"); sedative-, hypnotic-, or anxiolytic-induced anxiety disorder

("Anxiety Disorders"); sedative-, hypnotic-, or anxiolytic-induced sleep disorder ("SleepWake Disorders"); sedative-, hypnotic-, or anxiolytic-induced sexual dysfunction ("Sexual Dysfunctions"); and sedative-, hypnotic-, or anxiolytic-induced major or mild neurocognitive disorder ("Neurocognitive Disorders"). For sedative, hypnotic, or anxiolytic

intoxication delirium and sedative, hypnotic, or anxiolytic withdrawal delirium, see the

criteria and discussion of delirium in the chapter "Neurocognitive Disorders." These sedative-, hypnotic-, or anxiolytic-induced disorders are diagnosed instead of sedative, hypnotic, or anxiolytic intoxication or sedative, hypnotic, or anxiolytic withdrawal only when

the symptoms are sufficiently severe to warrant independent clinical attention.

Unspecified Sedative-, Hypnotic-,

or Anxiolytic-Related Disorder

292.9 (F13.99)

This category applies to presentations in which symptoms characteristic of a sedative-,

hypnotic-, or anxiolytic-related disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do

not meet the full criteria for any specific sedative-, hypnotic-, or anxiolytic-related disorder

or any of the disorders in the substance-related and addictive disorders diagnostic class.

Stimulant-Related Disorders

Stimulant Use Disorder

Stimulant Intoxication

Stimulant Withdrawal

Other Stimulant-Induced Disorders

Unspecified Stimulant-Related Disorder

Stimulant Use Disorder

Diagnostic Criteria

A. A pattern of amphetamine-type substance, cocaine, or other stimulant use leading to

clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. The stimulant is often taken in larger amounts or over a longer period than was intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control stimulant use.

3. A great deal of time is spent in activities necessary to obtain the stimulant, use the

stimulant, or recover from its effects.

4. Craving, or a strong desire or urge to use the stimulant.

5. Recurrent stimulant use resulting in a failure to fulfill major role obligations at work,

school, or home.

6. Continued stimulant use despite having persistent or recurrent social or inteφersonal problems caused or exacerbated by the effects of the stimulant.

7. Important social, occupational, or recreational activities are given up or reduced because of stimulant use.

8. Recurrent stimulant use in situations in which it is physically hazardous.

9. Stimulant use is continued despite knowledge of having a persistent or recurrent

physical or psychological problem that is likely to have been caused or exacerbated

by the stimulant.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the stimulant to achieve intoxication

or desired effect.

b. A markedly diminished effect with continued use of the same amount of the

stimulant.

Note: This criterion is not considered to be met for those taking stimulant medications solely under appropriate medical supervision, such as medications for attention-deficit/hyperactivity disorder or narcolepsy.

11. Withdrawal, as manifested by either of the following:

a. The characteristic withdrawal syndrome for the stimulant (refer to Criteria A and

B of the criteria set for stimulant withdrawal, p. 569).

b. The stimulant (or a closely related substance) is taken to relieve or avoid withdrawal symptoms.

Note; This criterion is not considered to be met for those taking stimulant medications solely under appropriate medical supervision, such as medications for attention-deficii'hyperactivity disorder or narcolepsy.

Specify if:

In early remission: After full criteria for stimulant use disorder were previously met,

none of the criteria for stimulant use disorder have been met for at least 3 months but

for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use the stimulant,” may be met).

In sustained remission: After full criteria for stimulant use disorder were previously

met, none of the criteria for stimulant use disorder have been met at any time during a

period of 12 months or longer (with the exception that Criterion A4, “Craving, or a

strong desire or urge to use the stimulant,” may be met).

Specify if:

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to stimulants is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If an amphetamine intoxication, amphetamine withdrawal, or another amphetamine-induced mental disorder is

also present, do not use the codes below for amphetamine use disorder. Instead, the comorbid amphetamine use disorder is indicated in the 4th character of the amphetamineinduced disorder code (see the coding note for amphetamine intoxication, amphetamine

withdrawal, or a specific amphetamine-induced mental disorder). For example, if there is

comorbid amphetamine-type or other stimulant-induced depressive disorder and amphetamine-type or other stimulant use disorder, only the amphetamine-type or other stimulantinduced depressive disorder code is given, with the 4th character indicating whether the

comorbid amphetamine-type or other stimulant use disorder is mild, moderate, or severe:

FI 5.14 for mild amphetamine-type or other stimulant use disorder with amphetamine-type

or other stimulant-induced depressive disorder or FI 5.24 for a moderate or severe amphetamine-type or other stimulant use disorder with amphetamine-type or other stimulantinduced depressive disorder. Similarly, if there is comorbid cocaine-induced depressive

disorder and cocaine use disorder, only the cocaine-induced depressive disorder code is

given, with the 4th character indicating whether the comorbid cocaine use disorder is mild,

moderate, or severe: F14.14 for mild cocaine use disorder with cocaine-induced depressive

disorder or FI 4.24 for a moderate or severe cocaine use disorder with cocaine-induced

depressive disorder.

Specify current severity:

Mild: Presence of 2-3 symptoms.

305.70 (FI 5.10) Amphetamine-type substance

305.60 (FI 4.10) Cocaine

305.70 (F I5.10) Other or unspecified stimulant

iVloderate: Presence of 4-5 symptoms.

304.40 (FI 5.20) Amphetamine-type substance

304.20 (FI 4.20) Cocaine

304.40 (F15.20) Other or unspecified stimulant

Severe: Presence of 6 or more symptoms.

304.40 (FI 5.20) Amphetamine-type substance

304.20 (FI 4.20) Cocaine

304.40 (FI 5.20) Other or unspecified stimulant

Specifiers

"In a controlled environment" applies as a further specifier of remission if the individual is

both in remission and in a controlled environment (i.e., in early remission in a controlled

environment or in sustained remission in a controlled environment). Examples of these

environments are closely supervised and substance-free jails, therapeutic communities,

and locked hospital units.

Diagnostic Features

The amphetamine and amphetamine-type stimulants include substances with a substituted-phenylethylamine structure, such as amphetamine, dextroamphetamine, and methamphetamine. Also included are those substances that are structurally different but have

similar effects, such as methylphenidate. These substances are usually taken orally or intravenously, although methamphetamine is also taken by the nasal route. In addition to

the synthetic amphetamine-type compounds, there are naturally occurring, plant-derived

stimulants such as khât. Amphetamines and other stimulants may be obtained by prescription for the treatment of obesity, attention-deficit/hyperactivity disorder, and narcolepsy.

Consequently, prescribed stimulants may be diverted into the illegal market. The effects of

amphetamines and amphetamine-like drugs are similar to those of cocaine, such that the

criteria for stimulant use disorder are presented here as a single disorder with the ability to

specify the particular stimulant used by the individual. Cocaine may be consumed in several preparations (e.g., coca leaves, coca paste, cocaine hydrochloride, and cocaine alkaloids such as freebase and crack) that differ in potency because of varying levels of purity

and speed of onset. However, in all forms of the substance, cocaine is the active ingredient.

Cocaine hydrochloride powder is usually "snorted" through the nostrils or dissolved in

water and injected intravenously.

Individuals exposed to amphetamine-type stimulants or cocaine can develop stimulant use disorder as rapidly as 1 week, although the onset is not always this rapid. Regardless of the route of administration, tolerance occurs with repeated use. Withdrawal

symptoms, particularly hypersomnia, increased appetite, and dysphoria, can occur and

can enhance craving. Most individuals with stimulant use disorder have experienced tolerance or withdrawal.

Use patterns and course are similar for disorders involving amphetamine-type stimulants and cocaine, as both substances are potent central nervous system stimulants with

similar psychoactive and sympathomimetic effects. Amphetamine-type stimulants are

longer acting than cocaine and thus are used fewer times per day. Usage may be chronic or

episodic, with binges punctuated by brief non-use periods. Aggressive or violent behavior

is common when high doses are smoked, ingested, or administered intravenously. Intense

temporary anxiety resembling panic disorder or generalized anxiety disorder, as well as

paranoid ideation and psychotic episodes that resemble schizophrenia, is seen with highdose use.

Withdrawal states are associated with temporary but intense depressive symptoms that

can resemble a major depressive episode; the depressive symptoms usually resolve within

1 week. Tolerance to amphetamine-type stimulants develops and leads to escalation of the

dose. Conversely, some users of amphetamine-type stimulants develop sensitization,

characterized by enhanced effects.

Associated Features Supporting Diagnosis

When injected or smoked, stimulants typically produce an instant feeling of well-being,

confidence, and euphoria. Dramatic behavioral changes can rapidly develop with stimulant use disorder. Chaotic behavior, social isolation, aggressive behavior, and sexual dysfunction can result from long-term stimulant use disorder.

Individuals v^ith acute intoxication may present with rambling speech, headache, transient ideas of reference, and tinnitus. There may be paranoid ideation, auditory hallucinations in a clear sensorium, and tactile hallucinations, which the individual usually

recognizes as drug effects. Threats or acting out of aggressive behavior may occur. Depression, suicidal ideation, irritability, anhedonia, emotional lability, or disturbances in attention and concentration commonly occur during withdrawal. Mental disturbances associated

with cocaine use usually resolve hours to days after cessation of use but can persist for

1 month. Physiological changes during stimulant withdrawal are opposite to those of the

intoxication phase, sometimes including bradycardia. Temporary depressive symptoms

may meet symptomatic and duration criteria for major depressive episode. Histories consistent with repeated panic attacks, social anxiety disorder (social phobia)-like behavior,

and generalized anxiety-like syndromes are common, as are eating disorders. One extreme instance of stimulant toxicity is stimulant-induced psychotic disorder, a disorder

that resembles schizophrenia, with delusions and hallucinations.

Individuals with stimulant use disorder often develop conditioned responses to drugrelated stimuli (e.g., craving on seeing any white powderlike substance). These responses

contribute to relapse, are difficult to extinguish, and persist after detoxification.

Depressive symptoms with suicidal ideation or behavior can occur and are generally

the most serious problems seen during stimulant withdrawal.

Prevalence

Stimulant use disorder: amphetamine-type stimulants. Estimated 12-month prevalence

of amphetamine-type stimulant use disorder in the United States is 0.2% among 12- to 17-

year-olds and 0.2% among individuals 18 years and older. Rates are similar among adult

males and females (0.2%), but among 12- to 17-year-olds, the rate for females (0.3%) is

greater than that for males (0.1%). Intravenous stimulant use has a male-to-female ratio of

3:1 or 4:1, but rates are more balanced among non-injecting users, with males representing

54% of primary treatment admissions. Twelve-month prevalence is greater among 18- to

29-year-olds (0.4%) compared with 45- to 64-year-olds (0.1%). For 12- to 17-year-olds, rates

are highest among whites and African Americans (0.3%) compared with Hispanics (0.1%)

and Asian Americans and Pacific Islanders (0.01%), with amphetamine-type stimulant use

disorder virtually absent among Native Americans. Among adults, rates are highest among

Native Americans and Alaska Natives (0.6%) compared with whites (0.2%) and Hispanics

(0.2%), with amphetamine-type stimulant use disorder virtually absent among African

Americans and Asian Americans and Pacific Islanders. Past-year nonprescribed use of

prescription stimulants occurred among 5%-9% of children through high school, with

5%-35% of college-age persons reporting past-year use.

Stimulant use disorder: cocaine. Estimated 12-month prevalence of cocaine use disorder

in the United States is 0.2% among 12- to 17-year-olds and 0.3% among individuals 18 years

and older. Rates are higher among males (0.4%) than among females (0.1%). Rates are

highest among 18- to 29-year-olds (0.6%) and lowest among 45- to 64-year-olds (0.1%). Among

adults, rates are greater among Native Americans (0.8%) compared with African Americans (0.4%), Hispanics (0.3%), whites (0.2%), and Asian Americans and Pacific Islanders

(0.1%). In contrast, for 12- to 17-year-olds, rates are similar among Hispanics (0.2%), whites

(0.2%), and Asian Americans and Pacific Islanders (0.2%); and lower among African Americans (0.02%); with cocaine use disorder virtually absent among Native Americans and

Alaska Natives.

Development and Course

Stimulant use disorders occur throughout all levels of society and are more common among

individuals ages 12-25 years compared with individuals 26 years and older. First regular use

among individuals in treatment occurs, on average, at approximately age 23 years. For primary methamphetamine-primary treatment admissions, Ûie average age is 31 years.

Some individuals begin stimulant use to control weight or to improve performance in

school, work, or athletics. This includes obtaining medications such as methylphenidate or

amphetamine salts prescribed to others for the treatment of attention-deficit/hyperactivity disorder. Stimulant use disorder can develop rapidly with intravenous or smoked

administration; among primary admissions for amphetamine-type stimulant use, 66% reported smoking, 18% reported injecting, and 10% reported snorting.

Patterns of stimulant administration include episodic or daily (or almost daily) use.

Episodic use tends to be separated by 2 or more days of non-use (e.g., intense use over a

weekend or on one or more weekdays). "'Binges" involve continuous high-dose use over

hours or days and are often associated with physical dependence. Binges usually terminate only when stimulant supplies are depleted or exhaustion ensues. Chronic daily use

may involve high or low doses, often with an increase in dose over time.

Stimulant smoking and intravenous use are associated with rapid progression to severe-level stimulant use disorder, often occurring over weeks to months. Intranasal use of

cocaine and oral use of amphetamine-type stimulants result in more gradual progression

occurring over months to years. With continuing use, there is a diminution of pleasurable

effects due to tolerance and an increase in dysphoric effects.

Risk and Prognostic Factors

Temperamental. Comorbid bipolar disorder, schizophrenia, antisocial personality disorder, and other substance use disorders are risk factors for developing stimulant use disorder

and for relapse to cocaine use in treatment samples. Also, impulsivity and similar personality

traits may affect treatment outcomes. Childhood conduct disorder and adult antisocial personality disorder are associated with the later development of stimulant-related disorders.

Environmental. Predictors of cocaine use among teenagers include prenatal cocaine exposure, postnatal cocaine use by parents, and exposure to community violence during

childhood. For youths, especially females, risk factors include living in an unstable home

environment, having a psychiatric condition, and associating with dealers and users.

Culture-Reiated Diagnostic issues

Stimulant use-attendant disorders affect all racial/ethnic, socioeconomic, age, and gender

groups. Diagnostic issues may be related to societal consequences (e.g., arrest, school suspensions, employment suspension). Despite small variations, cocaine and other stimulant

use disorder diagnostic criteria perform equally across gender and race/ethnicity groups.

Chronic use of cocaine impairs cardiac left ventricular function in African Americans.

Approximately 66% of individuals admitted for primary methamphetamine/amphetamine-related disorders are non-Hispanic white, followed by 21% of Hispanic origin, 3%

Asian and Pacific Islander, and 3% non-Hispanic black.

Diagnostic iVlaricers

Benzoylecgonine, a metabolite of cocaine, typically remains in the urine for 1-3 days after

a single dose and may be present for 7-12 days in individuals using repeated high doses.

Mildly elevated liver function tests can be present in cocaine injectors or users with concomitant alcohol use. There are no neurobiological markers of diagnostic utility. Discontinuation of chronic cocaine use may be associated with electroencephalographic changes,

suggesting persistent abnormalities; alterations in secretion patterns of prolactin; and

downregulation of dopamine receptors.

Short-half-life amphetamine-type stimulants (MDMA [3,4-methylenedioxy-JV-methylamphetamine], methamphetamine) can be detected for 1-3 days, and possibly up to 4 days

depending on dosage and nnetabolism. Hair samples can be used to detect presence of amphetamine-type stimulants for up to 90 days. Other laboratory findings, as well as physical

findings and other medical conditions (e.g., weight loss, malnutrition; poor hygiene), are

similar for both cocaine and amphetamine-type stimulant use disorder.

Functional Consequences of Stimulant Use Disorder

Various medical conditions may occur depending on the route of administration. Intranasal users often develop sinusitis, irritation, bleeding of the nasal mucosa, and a perforated

nasal septum. Individuals who smoke the drugs are at increased risk for respiratory problems (e.g., coughing, bronchitis, and pneumonitis). Injectors have puncture marks and

"tracks," most commonly on their forearms. Risk of HIV infection increases with frequent

intravenous injections and unsafe sexual activity. Other sexually transmitted diseases,

hepatitis, and tuberculosis and other lung infections are also seen. Weight loss and malnutrition are common.

Chest pain may be a common symptom during stimulant intoxication. Myocardial infarction, palpitations and arrhythmias, sudden death from respiratory or cardiac arrest,

and stroke have been associated with stimulant use among young and otherwise healthy

individuals. Seizures can occur with stimulant use. Pneumothorax can result from performing Valsalva-like maneuvers done to better absorb inhaled smoke. Traumatic injuries

due to violent behavior are common among individuals trafficking drugs. Cocaine use is

associated with irregularities in placental blood flow, abruptio placentae, premahire labor

and delivery, and an increased prevalence of infants with very low birth weights.

Individuals with stimulant use disorder may become involved in theft, prostitution, or

drug dealing in order to acquire drugs or money for drugs.

Neurocognitive impairment is common among methamphetamine users. Oral health

problems include "meth mouth" with gum disease, tooth decay, and mouth sores related

to the toxic effects of smoking the drug and to bruxism while intoxicated. Adverse pulmonary effects appear to be less common for amphetamine-type stimulants because they are

smoked fewer times per day. Emergency department visits are common for stimulant-related mental disorder symptoms, injury, skin infections, and dental pathology.

Differential Diagnosis

Primary mental disorders. Stimulant-induced disorders may resemble primary mental

disorders (e.g., major depressive disorder) (for discussion of this differential diagnosis, see

"Stimulant Withdrawal"). The mental disturbances resulting from the effects of stimulants

should be distinguished from the symptoms of schizophrenia; depressive and bipolar disorders; generalized anxiety disorder; and panic disorder.

Phencyclidine intoxication. Intoxication with phencyclidine ("PCP" or "angel dust") or

synthetic "designer drugs" such as mephedrone (known by different names, including

"bath salts") may cause a similar clinical picture and can only be distinguished from stimulant intoxication by the presence of cocaine or amphetamine-type substance metabolites

in a urine or plasma sample.

Stimulant intoxication and withdrawal. Stimulant intoxication and withdrawal are distinguished from the other stimulant-induced disorders (e.g., anxiety disorder, with onset

during intoxication) because the symptoms in the latter disorders predominate the clinical

presentation and are severe enough to warrant independent clinical attention.

Comorbidity

Stimulant-related disorders often co-occur with other substance use disorders, especially

those involving substances with sedative properties, which are often taken to reduce in-

somnia, nervousness, and other unpleasant side effects. Cocaine users often use alcohol,

while amphetamine-type stimulant users often use cannabis. Stimulant use disorder may

be associated with posttraumatic stress disorder, antisocial personality disorder, attention-deficit/hyperactivity disorder, and gambling disorder. Cardiopulmonary problems

are often present in individuals seeking treatment for cocaine-related problems, with chest

pain being the most common. Medical problems occur in response to adulterants used as

"cutting" agents. Cocaine users who ingest cocaine cut with levamisole, an antimicrobial

and veterinary medication, may experience agranulocytosis and febrile neutropenia.

Stimulant Intoxication

Diagnostic Criteria

A. Recent use of an amphetamine-type substance, cocaine, or other stimulant.

B. Clinically significant problematic behavioral or psychological changes (e.g., euphoria

or affective blunting: changes in sociability: hypervigilance: interpersonal sensitivity:

anxiety, tension, or anger; stereotyped behaviors: impaired judgment) that developed

during, or shortly after, use of a stimulant.

C. Two (or more) of the following signs or symptoms, developing during, or shortly after,

stimulant use:

1. Tachycardia or bradycardia.

2. Pupillary dilation.

3. Elevated or lowered blood pressure.

4. Perspiration or chills.

5. Nausea or vomiting.

6. Evidence of weight loss.

7. Psychomotor agitation or retardation.

8. Muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias.

9. Confusion, seizures, dyskinesias, dystonias, or coma.

D. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication with another substance.

Specify the specific intoxicant (i.e., amphetamine-type substance, cocaine, or other

stimulant).

Specify if:

Witli perceptual disturbances: This specifier may be noted when hallucinations with

intact reality testing or auditory, visual, or tactile illusions occur in the absence of a delirium.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

the stimulant is an amphetamine, cocaine, or other stimulant: whether there is a comorbid

amphetamine, cocaine, or other stimulant use disorder; and whether or not there are perceptual disturbances.

For amphetamine, cocaine, or other stimulant intoxication, without perceptual disturbances: If a mild amphetamine or other stimulant use disorder is comorbid, the ICD10-CM code is FI 5.129, and if a moderate or severe amphetamine or other stimulant use

disorder is comorbid, the ICD-10-CM code is F I 5.229. If there is no comorbid amphetamine or other stimulant use disorder, then the ICD-10-CM code is F15.929. Similarly, if

a mild cocaine use disorder is comorbid, the ICD-10-CM code is FI 4.129, and if a moderate or severe cocaine use disorder is comorbid, the ICD-10-CM code is F I4.229. If

there is no comorbid cocaine use disorder, then the ICD-10-CM code is F14.929.

For amphetamine, cocaine, or other stimulant intoxication, with perceptual disturbances: If a mild amphetamine or other stimulant use disorder is comorbid, the ICD-10-

CM code is FI 5.122, and if a moderate or severe amphetamine or other stimulant use

disorder is comorbid, the ICD-10-CM code is FI 5.222. If there is no comorbid amphetamine or other stimulant use disorder, then the ICD-10-CM code is F15.922. Similarly, if

a mild cocaine use disorder is comorbid, the ICD-10-CM code is FI 4.122, and if a moderate or severe cocaine use disorder is comorbid, the ICD-10-CM code is FI 4.222. If

there is no comorbid cocaine use disorder, then the ICD-10-CM code is F14.922.

Diagnostic Features

The essential feature of stimulant intoxication, related to amphetamine-type stimulants

and cocaine, is the presence of clinically significant behavioral or psychological changes

that develop during, or shortly after, use of stimulants (Criteria A and B). Auditory hallucinations may be prominent, as may paranoid ideation, and these symptoms must be distinguished from an independent psychotic disorder such as schizophrenia. Stimulant

intoxication usually begins with a "high" feeling and includes one or more of the following: euphoria with enhanced vigor, gregariousness, hyperactivity, restlessness, hypervigilance, interpersonal sensitivity, talkativeness, anxiety, tension, alertness, grandiosity,

stereotyped and repetitive behavior, anger, impaired judgment, and, in the case of chronic

intoxication, affective blunting with fatigue or sadness and social withdrawal. These behavioral and psychological changes are accompanied by two or more of the following

signs and symptoms that develop during or shortly after stimulant use: tachycardia or bradycardia; pupillary dilation; elevated or lowered blood pressure; perspiration or chills;

nausea or vomiting; evidence of weight loss; psychomotor agitation or retardation; muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias; and confusion, seizures, dyskinesias, dystonias, or coma (Criterion C). Intoxication, either acute or

chronic, is often associated with impaired social or occupational functioning. Severe intoxication can lead to convulsions, cardiac arrhythmias, hyperpyrexia, and death. For the

diagnosis of stimulant intoxication to be made, the symptoms must not be attributable

to another medical condition and not better explained by another mental disorder (Criterion D). While stimulant intoxication occurs in individuals with stimulant use disorders, intoxication is not a criterion for stimulant use disorder, which is confirmed by the presence

of two of the 11 diagnostic criteria for use disorder.

Associated Features Supporting Diagnosis

The magnitude and direction of the behavioral and physiological changes depend on many

variables, including the dose used and the characteristics of the individual using the substance or the context (e.g., tolerance, rate of absorption, chronicity of use, context in which

it is taken). Stimulant effects such as euphoria, increased pulse and blood pressure, and

psychomotor activity are most commonly seen. Depressant effects such as sadness, bradycardia, decreased blood pressure, and decreased psychomotor activity are less common

and generally emerge only with chronic high-dose use.

Differentiai Diagnosis

Stimulant-induced disorders. Stimulant intoxication is distinguished from the other

stimulant-induced disorders (e.g., stimulant-induced depressive disorder, bipolar disorder, psychotic disorder, anxiety disorder) because the severity of the intoxication symptoms exceeds that associated with the stimulant-induced disorders, and the symptoms

warrant independent clinical attention. Stimulant intoxication delirium would be distinguished by a disturbance in level of awareness and change in cognition.

Other mental disorders. Salient mental disturbances associated with stimulant intoxication should be distinguished from the symptoms of schizophrenia, paranoid type; bipolar and depressive disorders; generalized anxiety disorder; and panic disorder as

described in DSM-5.

Stimulant Withdrawal

Diagnostic Criteria

A. Cessation of (or reduction in) prolonged amphetamine-type substance, cocaine, or

other stimulant use.

B. Dysphoric mood and two (or more) of the following physiological changes, developing

within a few hours to several days after Criterion A:

1. Fatigue.

2. Vivid, unpleasant dreams.

3. Insomnia or hypersomnia.

4. Increased appetite.

5. Psychomotor retardation or agitation.

C. The signs or symptoms in Criterion B cause clinically significant distress or impairment

in social, occupational, or other important areas of functioning.

D. The signs or symptoms are not attributable to another medical condition and are not

better explained by another mental disorder, including intoxication or withdrawal from

another substance.

Specify tlie specific substance tiiat causes the withdrawai syndrome (i.e., amphetamine-type substance, cocaine, or other stimulant).

Coding note: The ICD-9-CM code is 292.0. The ICD-10-CM code depends on whether

the stimulant is an amphetamine, cocaine, or other stimulant. The ICD-10-CM code for

amphetamine or an other stimulant withdrawal is FI 5.23, and the ICD-10-CM for cocaine

withdrawal is F14.23. Note that the ICD-10-CM code indicates the comorbid presence of

a moderate or severe amphetamine, cocaine, or other stimulant use disorder, reflecting

the fact that amphetamine, cocaine, or other stimulant withdrawal can only occur in the

presence of a moderate or severe amphetamine, cocaine, or other stimulant use disorder.

It is not permissible to code a comorbid mild amphetamine, cocaine, or other stimulant use

disorder with amphetamine, cocaine, or other stimulant withdrawal._________________

Diagnostic Features

The essential feature of stimulant withdrawal is the presence of a characteristic withdrawal syndrome that develops within a few hours to several days after the cessation of

(or marked reduction in) stimulant use (generally high dose) that has been prolonged (Criterion A). The withdrawal syndrome is characterized by the development of dysphoric

mood accompanied by two or more of the following physiological changes: fatigue, vivid

and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor

retardation or agitation (Criterion B). Bradycardia is often present and is a reliable measure of stimulant withdrawal.

Anhedonia and drug craving can often be present but are not part of the diagnostic criteria. These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion C). The symptoms must not be

attributable to another medical condition and are not better explained by another mental

disorder (Criterion D).

Associated Features Supporting Diagnosis

Acute withdrawal symptoms ("a crash") are often seen after periods of repetitive high-dose

use ("runs" or 'l^inges"). These periods are characterized by intense and unpleasant feelings of

lassitude and depression and increased appetite, generally requiring several days of rest and

recuperation. Depressive symptoms with suicidal ideation or behavior can occur and are generally the most serious problems seen during "crashing" or other forms of stimulant withdrawal. The majority of individuals with stimulant use disorder experience a withdrawal

syndrome at some point, and virtually all individuals with the disorder report tolerance.

Differential Diagnosis

Stimulant use disorder and other stimulant-induced disorders. Stimulant withdrawal

is distinguished from stimulant use disorder and from the other stimulant-induced disorders (e.g., stimulant-induced intoxication delirium, depressive disorder, bipolar disorder,

psychotic disorder, anxiety disorder, sexual dysfunction, sleep disorder) because the

symptoms of withdrawal predominate the clinical presentation and are severe enough to

warrant independent clinical attention.

Other Stimulant-Induced Disorders

The following stimulant-induced disorders (which include amphetamine-, cocaine-, and

other stimulant-induced disorders) are described in other chapters of the manual with disorders with which they share phenomenology (see the substance/medication-induced

mental disorders in these chapters): stimulant-induced psychotic disorder ("Schizophrenia

Spectrum and Other Psychotic Disorders"); stimulant-induced bipolar disorder ("Bipolar

and Related Disorders"); stimulant-induced depressive disorder ("Depressive Disorders");

stimulant-induced anxiety disorder ("Anxiety Disorders"); stimulant-induced obsessivecompulsive disorder ("Obsessive-Compulsive and Related Disorders"); stimulant-induced

sleep disorder ("Sleep-Wake Disorders"); and stimulant-induced sexual dysfunction ("Sexual Dysfunctions"). For stimulant intoxication delirium, see the criteria and discussion of

delirium in the chapter "Neurocognitive Disorders." These stimulant-induced disorders

are diagnosed instead of stimulant intoxication or stimulant withdrawal only when the

symptoms are sufficiently severe to warrant independent clinical attention.

Unspecified Stimulant-Related Disorder

This category applies to presentations in which symptoms characteristic of a stimulantrelated disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria

for any specific stimulant-related disorder or any of the disorders in the substance-related

and addictive disorders diagnostic class.

Coding note: The ICD-9-CM code is 292.9. The ICD-10-CM code depends on whether

the stimulant is an amphetamine, cocaine, or another stimulant. The ICD-10-CM code for

an unspecified amphetamine- or other stimulant-related disorder is F15.99. The ICD-10-

CM code for an unspecified cocaine-related disorder is FI 4.99.

Tobacco-Related Disorders

Tobacco Use Disorder

Tobacco Withdrawal

Other Tobacco-Induced Disorders

Unspecified Tobacco-Related Disorder

Tobacco Use Disorder

Diagnostic Criteria

A. A problematic pattern of tobacco use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. Tobacco is often taken in larger amounts or over a longer period than was intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control tobacco use.

3. A great deal of time is spent in activities necessary to obtain or use tobacco.

4. Craving, or a strong desire or urge to use tobacco.

5. Recurrent tobacco use resulting in a failure to fulfill major role obligations at work,

school, or home (e.g., interference with work).

6. Continued tobacco use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of tobacco (e.g., arguments

with others about tobacco use).

7. important social, occupational, or recreational activities are given up or reduced because of tobacco use.

8. Recurrent tobacco use in situations in which it is physically hazardous (e.g., smoking in bed).

9. Tobacco use is continued despite knowledge of having a persistent or recurrent

physical or psychological problem that is likely to have been caused or exacerbated

by tobacco.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of tobacco to achieve the desired effect.

b. A markedly diminished effect with continued use of the same amount of tobacco.

11. Withdrawal, as manifested by either of the following:

a. The characteristic withdrawal syndrome for tobacco (refer to Criteria A and B of

the criteria set for tobacco withdrawal).

b. Tobacco (or a closely related substance, such as nicotine) is taken to relieve or

avoid withdrawal symptoms.

Specify if:

In early remission: After full criteria for tobacco use disorder were previously met,

none of the criteria for tobacco use disorder have been met for at least 3 months but

for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use tobacco,” may be met).

In sustained remission: After full criteria for tobacco use disorder were previously

met, none of the criteria for tobacco use disorder have been met at any time during a

period of 12 months or longer (with the exception that Criterion A4, “Craving, or a

strong desire or urge to use tobacco," may be met).

Specify if:

On maintenance therapy: The individual is taking a long-term maintenance medication, such as nicotine replacement medication, and no criteria for tobacco use disorder

have been met for that class of medication (except tolerance to, or withdrawal from,

the nicotine replacement medication).

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to tobacco is restricted.

Coding based on current severity: Note for ICD-10-CM codes; If a tobacco withdrawal or

tobacco-induced sleep disorder is also present, do not use the codes below for tobacco use

disorder. Instead, the comorbid tobacco use disorder is indicated in the 4th character of the

tobacco-induced disorder code (see the coding note for tobacco withdrawal or tobaccoinduced sleep disorder). For example, if there is comorbid tobacco-induced sleep disorder and

tobacco use disorder, only the tobacco-induced sleep disorder code is given, with the 4th character indicating whether the comorbid tobacco use disorder is moderate or severe: F17.208

for moderate or severe tobacco use disorder with tobacco-induced sleep disorder. It is not permissible to code a comorbid mild tobacco use disorder with a tobacco-induced sleep disorder.

Specify current severity:

305.1 (Z72.0) Mild: Presence of 2-3 symptoms.

305.1 (F I7.200) Moderate: Presence of 4-5 symptoms.

305.1 (F I 7.200) Severe: Presence of 6 or more symptoms.

Specifiers

"On maintenance therapy" applies as a further specifier to individuals being maintained on

other tobacco cessation medication (e.g., bupropion, varenicline) and as a further specifier of

remission if the individual is both in remission and on maintenance therapy. "In a controlled

environment" applies as a further specifier of remission if the individual is both in remission

and in a controlled environment (i.e., in early remission in a controlled environment or in sustained remission in a controlled environment). Examples of these environments are closely supervised and substance-free jails, therapeutic conununities, and locked hospital units.

Diagnostic Features

Tobacco use disorder is common among individuals who use cigarettes and smokeless tobacco daily and is uncommon among individuals who do not use tobacco daily or who use

nicotine medications. Tolerance to tobacco is exemplified by the disappearance of nausea

and dizziness after repeated intake and with a more intense effect of tobacco the first time

it is used during the day. Cessation of tobacco use can produce a well-defined withdrawal

syndrome. Many individuals with tobacco use disorder use tobacco to relieve or to avoid

withdrawal symptoms (e.g., after being in a situation where use is restricted). Many individuals who use tobacco have tobacco-related physical symptoms or diseases and continue to smoke. The large majority report craving when they do not smoke for several hours.

Spending excessive time using tobacco can be exemplified by chain-smoking (i.e., smoking one cigarette after another with no time between cigarettes). Because tobacco sources

are readily and legally available, and because nicotine intoxication is very rare, spending a

great deal of time attempting to procure tobacco or recovering from its effects is uncommon. Giving up important social, occupational, or recreational activities can occur when

an individual forgoes an activity because it occurs in tobacco use-restricted areas. Use of

tobacco rarely results in failure to fulfill major role obligations (e.g., interference with

work, interference with home obligations), but persistent social or inteφersonal problems

(e.g., having arguments with others about tobacco use, avoiding social situations because

of others' disapproval of tobacco use) or use that is physically hazardous (e.g., smoking in

bed, smoking around flammable chemicals) occur at an intermediate prevalence. Although

these criteria are less often endorsed by tobacco users, if endorsed, they can indicate a

more severe disorder.

Associated Features Supporting Diagnosis

Smoking within 30 minutes of waking, smoking daily, smoking more cigarettes per day,

and waking at night to smoke are associated with tobacco use disorder. Environmental

cues can evoke craving and withdrawal. Serious medical conditions, such as lung and

other cancers, cardiac and pulmonary disease, perinatal problems, cough, shortness of

breath, and accelerated skin aging, often occur.

Prevalence

Cigarettes are the most commonly used tobacco product, representing over 90% of tobacco/nicotine use. In the United States, 57% of adults have never been smokers, 22% are

former smokers, and 21% are current smokers. Approximately 20% of current U.S. smokers are nondaily smokers. The prevalence of smokeless tobacco use is less than 5%, and the

prevalence of tobacco use in pipes and cigars is less than 1%.

DSM-IV nicotine dependence criteria can be used to estimate the prevalence of tobacco

use disorder, but since they are a subset of tobacco use disorder criteria, the prevalence of

tobacco use disorder will be somewhat greater. The 12-month prevalence of DSM-IV nicotine dependence in the United States is 13% among adults age 18 years and older. Rates

are similar among adult males (14%) and females (12%) and decline in age from 17%

among 18- to 29-year-olds to 4% among individuals age 65 years and older. The prevalence

of current nicotine dependence is greater among Native American and Alaska Natives

(23%) than among whites (14%) but is less among African Americans (10%), Asian Americans and Pacific Islanders (6%), and Hispanics (6%). The prevalence among current daily

smokers is approximately 50%.

In many developing nations, the prevalence of smoking is much greater in males than

in females, but this is not the case in developed nations. However, there often is a lag in the

demographic transition such that smoking increases in females at a later time.

Development and Course

The majority of U.S. adolescents experiment with tobacco use, and by age 18 years, about

20% smoke at least monthly. Most of these individuals become daily tobacco users. Initiation of smoking after age 21 years is rare. In general, some of the tobacco use disorder criteria symptoms occur soon after beginning tobacco use, and many individuals' pattern of

use meets current tobacco use disorder criteria by late adolescence. More than 80% of individuals who use tobacco attempt to quit at some time, but 60% relapse within 1 week

and less than 5% remain abstinent for life. However, most individuals who use tobacco

make multiple attempts such that one-half of tobacco users eventually abstain. Individuals

who use tobacco who do quit usually do not do so until after age 30 years. Although nondaily smoking in the United States was previously rare, it has become more prevalent in

the last decade, especially among younger individuals who use tobacco.

Risic and Prognostic Factors

Temperamental. Individuals with externalizing personality traits are more likely to

initiate tobacco use. Children with attention-deficit/hyperactivity disorder or conduct

disorder, and adults with depressive, bipolar, anxiety, personality, psychotic, or other

substance use disorders, are at higher risk of starting and continuing tobacco use and of tobacco use disorder.

Environmental. Individuals with low incomes and low educational levels are more likely

to initiate tobacco use and are less likely to stop.

Genetic and physiological. Genetic factors contribute to the onset of tobacco use, the

continuation of tobacco use, and the development of tobacco use disorder, with a degree of

heritability equivalent to that observed with other substance use disorders (i.e., about

50%). Some of this risk is specific to tobacco, and some is common with the vulnerability to

developing any substance use disorder.

Culture-Related Diagnostic Issues

Cultures and subcultures vary widely in their acceptance of the use of tobacco. The prevalence of tobacco use declined in the United States from the 1960s through the 1990s, but

this decrease has been less evident in African American and Hispanic populations. Also,

smoking in developing countries is more prevalent than in developed nations. The degree

to which these cultural differences are due to income, education, and tobacco control activities in a country is unclear. Non-Hispanic white smokers appear to be more likely to

develop tobacco use disorder than are smokers. Some ethnic differences may be biologically based. African American males tend to have higher nicotine blood levels for a given

number of cigarettes, and this might contribute to greater difficulty in quitting. Also, the

speed of nicotine metabolism is significantly different for whites compared with African

Americans and can vary by genotypes associated with ethnicities.

Diagnostic Markers

Carbon monoxide in the breath, and nicotine and its metabolite cotinine in blood, saliva, or

urine, can be used to measure the extent of current tobacco or nicotine use; however, these

are only weakly related to tobacco use disorder.

Functional Consequences of Tobacco Use Disorder

Medical consequences of tobacco use often begin when tobacco users are in their 40s and

usually become progressively more debilitating over time. One-half of smokers who do

not stop using tobacco will die early from a tobacco-related illness, and smoking-related

morbidity occurs in more than one-half of tobacco users. Most medical conditions result

from exposure to carbon monoxide, tars, and other non-nicotine components of tobacco.

The major predictor of reversibility is duration of smoking. Secondhand smoke increases

the risk of heart disease and cancer by 30%. Long-term use of nicotine medications does

not appear to cause medical harm.

Comorbidity

The most common medical diseases from smoking are cardiovascular illnesses, chronic

obstructive pulmonary disease, and cancers. Smoking also increases perinatal problems,

such as low birth weight and miscarriage. The most common psychiatric comorbidities are

alcohol/substance, depressive, bipolar, anxiety, personality, and attention-deficit/hyperactivity disorders. In individuals with current tobacco use disorder, the prevalence of current alcohol, drug, anxiety, depressive, bipolar, and personality disorders ranges from

22% to 32%. Nicotine-dependent smokers are 2.7-8.1 times more likely to have these disorders than nondependent smokers, never-smokers, or ex-smokers.

Tobacco Withdrawal

_____________ ^____________________________________________________________

Diagnostic Criteria 292.0 (F17.203)

A. Daily use of tobacco for at least several weeks.

B. Abrupt cessation of tobacco use, or reduction in the amount of tobacco used, followed

within 24 hours by four (or more) of the following signs or symptoms:

1. Irritability, frustration, or anger.

2. Anxiety.

3. Difficulty concentrating.

4. Increased appetite.

5. Restlessness.

6. Depressed mood.

7. Insomnia.

C. The signs or symptoms in Criterion B cause clinically significant distress or impairment

in social, occupational, or other important areas of functioning.

D. The signs or symptoms are not attributed to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.

Coding note: The ICD-9-CM code is 292.0. The ICD-10-CM code for tobacco withdrawal

is F17.203. Note that the ICD-10-CM code indicates the comorbid presence of a moderate

or severe tobacco use disorder, reflecting the fact that tobacco withdrawal can only occur

in the presence of a moderate or severe tobacco use disorder. It is not permissible to code

a comorbid mild tobacco use disorder with tobacco withdrawal.____________________

Diagnostic Features

Withdrawal symptoms impair the ability to stop tobacco use. The symptoms after abstinence from tobacco are in large part due to nicotine deprivation. Symptoms are much

more intense among individuals who smoke cigarettes or use smokeless tobacco than

among those who use nicotine medications. This difference in symptom intensity is likely

due to the more rapid onset and higher levels of nicotine with cigarette smoking. Tobacco

withdrawal is common among daily tobacco users who stop or reduce but can also occur

among nondaily users. Typically, heart rate decreases by 5-12 beats per minute in the first

few days after stopping smoking, and weight increases an average of 4-7 lb (2-3 kg) over

the first year after stopping smoking. Tobacco withdrawal can produce clinically significant mood changes and functional impairment.

Associated Features Supporting Diagnosis

Craving for sweet or sugary foods and impaired performance on tasks requiring vigilance

are associated with tobacco withdrawal. Abstinence can increase constipation, coughing,

dizziness, dreaming/nightmares, nausea, and sore throat. Smoking increases the metabolism of many medications used to treat mental disorders; thus, cessation of smoking can

increase the blood levels of these medications, and this can produce clinically significant

outcomes. This effect appears to be due not to nicotine but rather to other compounds in

tobacco.

Prevalence

Approximately 50% of tobacco users who quit for 2 or more days will have symptoms that

meet criteria for tobacco withdrawal. The most commonly endorsed signs and symptoms

are anxiety, irritability, and difficulty concentrating. The least commonly endorsed symptoms are depression and insomnia.

Development and Course

Tobacco withdrawal usually begins within 24 hours of stopping or cutting down on tobacco use, peaks at 2-3 days after abstinence, and lasts 2-3 weeks. Tobacco withdrawal

symptoms can occur among adolescent tobacco users, even prior to daily tobacco use. Prolonged symptoms beyond 1 month are uncommon.

Risk and Prognostic Factors

Temperamental. Smokers with depressive disorders, bipolar disorders, anxiety disorders, attention-deficit/hyperactivity disorder, and other substance use disorders have

more severe withdrawal.

Genetic and physiological. Genotype can influence the probability of withdrawal upon

abstinence.

Diagnostic Markers

Carbon monoxide in the breath, and nicotine and its metabolite cotinine in blood, saliva, or

urine, can be used to measure the extent of tobacco or nicotine use but are only weakly related to tobacco withdrawal.

Functional Consequences of Tobacco Withdrawal

Abstinence from cigarettes can cause clinically significant distress. Withdrawal impairs

the ability to stop or control tobacco use. Whether tobacco withdrawal can prompt a new

mental disorder or recurrence of a mental disorder is debatable, but if this occurs, it would

be in a small minority of tobacco users.

Differential Diagnosis

The symptoms of tobacco withdrawal overlap with those of other substance withdrawal

syndromes (e.g., alcohol withdrawal; sedative, hypnotic, or anxiolytic withdrawal; stimulant withdrawal; caffeine withdrawal; opioid withdrawal); caffeine intoxication; anxiety,

depressive, bipolar, and sleep disorders; and medication-induced akathisia. Admission to

smoke-free inpatient units or voluntary smoking cessation can induce withdrawal symptoms that mimic, intensify, or disguise other disorders or adverse effects of medications

used to treat mental disorders (e.g., irritability thought to be due to alcohol withdrawal

could be due to tobacco withdrawal). Reduction in symptoms with the use of nicotine

medications confirms the diagnosis.

Other Tobacco-Induced Disorders

Tobacco-induced sleep disorder is discussed in the chapter "Sleep-Wake Disorders" (see

''Substance/Medication-Induced Sleep Disorder").

Unspecified Tobacco-Related Disorder

^ 292.9 (F17.209)

This category applies to presentations in which symptoms characteristic of a tobaccorelated disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria

for any specific tobacco-related disorder or any of the disorders in the substance-related

and addictive disorders diagnostic class.

Other (or Unknown)

Substance-Related Disorders

Other (or Unknown) Substance Use Disorder

Other (or Unknown) Substance Intoxication

Other (or Unknown) Substance Withdrawal

Other (or Unknown) Substance-Induced Disorders

Unspecified Other (or Unknown) Substance-Related Disorder

Other (or Unknown) Substance Use Disorder

Diagnostic Criteria

A. A problematic pattern of use of an intoxicating substance not able to be classified

within the alcohol; caffeine; cannabis; hallucinogen (phencyclidine and others); inhalant; opioid; sedative, hypnotic, or anxiolytic; stimulant; or tobacco categories and leading to clinically significant impairment or distress, as manifested by at least two of the

following, occurring within a 12-month period:

1. The substance is often taken in larger amounts or over a longer period than was

intended.

2. There is a persistent desire or unsuccessful efforts to cut down or control use of the

substance.

3. A great deal of time is spent in activities necessary to obtain the substance, use the

substance, or recover from its effects.

4. Craving, or a strong desire or urge to use the substance.

5. Recurrent use of the substance resulting in a failure to fulfill major role obligations

at work, school, or home.

6. Continued use of the substance despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of its use.

7. Important social, occupational, or recreational activities are given up or reduced because of use of the substance.

8. Recurrent use of the substance in situations in which it is physically hazardous.

9. Use of the substance is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.

10. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the substance to achieve intoxication

or desired effect.

b. A markedly diminished effect with continued use of the same amount of the substance.

11. Withdrawal, as manifested by either of the following:

a. The characteristic withdrawal syndrome for other (or unknown) substance (refer to

Criteria A and B of the criteria sets for other [or unknown] substance withdrawal,

p. 583).

b. The substance (or a closely related substance) is taken to relieve or avoid withdrawal symptoms.

Specify if:

In early remission: After full criteria for other (or unknown) substance use disorder were

previously met, none of the criteria for other (or unknown) substance use disorder have

been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use the substance,” may be met).

In sustained remission: After full criteria for other (or unknown) substance use disorder were previously met, none of the criteria for other (or unknown) substance use disorder have been met at any time during a period of 12 months or longer (with the

exception that Criterion A4, “Craving, or a strong desire or urge to use the substance,”

may be met).

Specify if:

In a controlled environment: This additional specifier is used if the individual is in an

environment where access to the substance is restricted.

Coding based on current severity: Note for ICD-10-CM codes: If an other (or unknown) substance intoxication, other (or unknown) substance withdrawal, or another other (or unknown)

substance-induced mental disorder is present, do not use the codes below for other (or unknown) substance use disorder. Instead, the comorbid other (or unknown) substance use disorder is indicated in the 4th character of the other (or unknown) substance-induced disorder

code (see the coding note for other (or unknown) substance intoxication, other (or unknown)

substance withdrawal, or specific other (or unknown) substance-induced mental disorder).

For example, if there is comotbid other (or unknown) substance-induced depressive disorder

and other (or unknown) substance use disorder, only the other (or unknown) substanceinduced depressive disorder code is given, with the 4th character indicating whether the comorbid other (or unknown) substance use disorder is mild, moderate, or severe: FI 9.14 for

other (or unknown) substance use disorder with other (or unknown) substance-induced depressive disorder or FI 9.24 for a moderate or severe other (or unknown) substance use disorder with other (or unknown) substance-induced depressive disorder.

Specify current severity:

305.90 (FI 9.10) Mild: Presence of 2 -3 symptoms.

304.90 (FI 9.20) Moderate: Presence of 4-5 symptoms.

304.90 (F19.20) Severe: Presence of 6 or more symptoms.

Specifiers

"In a controlled environment" applies as a further specifier of remission if the individual is

both in remission and in a controlled environment (i.e., in early remission in a controlled

environment or in sustained remission in a controlled environment). Examples of these

environments are closely supervised and substance-free jails, therapeutic communities,

and locked hospital units.

Diagnostic Features

The diagnostic dass other (or unknown) substance use and related disorders comprises

substance-related disorders unrelated to alcohol; caffeine; cannabis; hallucinogens (phencyclidine and others); inhalants; opioids; sedative, hypnotics, or anxiolytics; stimulants

(including amphetamine and cocaine); or tobacco. Such substances include anabolic steroids; nonsteroidal anti-inflammatory drugs; cortisol; antiparkinsonian medications; antihistamines; nitrous oxide; amyl-, butyl-, or isobutyl-nitrites; betel nut, which is chewed

in many cultures to produce mild euphoria and a floating sensation; kava (from a South

Pacific pepper plant), which produces sedation, incoordination, weight loss, mild hepatitis, and lung abnormalities; or cathinones (including khât plant agents and synthetic chemical derivatives) that produce stimulant effects. Unknown substance-related disorders are

associated with unidentified substances, such as intoxications in which the individual cannot identify the ingested drug, or substance use disorders involving either new, black market drugs not yet identified or familiar drugs illegally sold under false names.

Other (or unknown) substance use disorder is a mental disorder in which repeated use

of an other or unknown substance typically continues, despite the individual's knowing

that the substance is causing serious problems for the individual. Those problems are reflected in the diagnostic criteria. When the substance is known, it should be reflected in the

name of the disorder upon coding (e.g., nitrous oxide use disorder).

Associated Features Supporting Diagnosis

A diagnosis of other (or unknown) substance use disorder is supported by the individual's

statement that the substance involved is not among the nine classes listed in this chapter; by recurring episodes of intoxication with negative results in standard drug screens (which may not

detect new or rarely used substances); or by the presence of symptoms characteristic of an unidentified substance that has newly appeared in the individual's community.

Because of increased access to nitrous oxide ("laughing gas"), membership in certain

populations is associated with diagnosis of nitrous oxide use disorder. The role of this gas

as an anesthetic agent leads to misuse by some medical and dental professionals. Its use as

a propellant for commercial products (e.g., whipped cream dispensers) contributes to

misuse by food service workers. With recent widespread availability of the substance in

"whippet" cartridges for use in home whipped cream dispensers, nitrous oxide misuse by

adolescents and young adults is significant, especially among those who also inhale volatile hydrocarbons. Some continuously using individuals, inhaling from as many as 240

whippets per day, may present with serious medical complications and mental conditions,

including myeloneuropathy, spinal cord subacute combined degeneration, peripheral

neuropathy, and psychosis. These conditions are also associated with a diagnosis of nitrous oxide use disorder.

Use of amyl-, butyl-, and isobutyl nitrite gases has been observed among homosexual

men and some adolescents, especially those with conduct disorder. Membership in these

populations may be associated with a diagnosis of amyl-, butyl-, or isobutyl-nitrite use disorder. However, it has not been determined that these substances produce a substance use

disorder. Despite tolerance, these gases may not alter behavior through central effects, and

they may be used only for their peripheral effects.

Substance use disorders generally are associated with elevated risks of suicide, but there

is no evidence of unique risk factors for suicide with other (or unknown) substance use

disorder.

Prevaience

Based on extremely limited data, the prevalence of other (or unknown) substance use disorder

is likely lower than that of use disorders involving the nine substance classes in this chapter.

Development and Course

No single pattern of development or course characterizes the pharmacologically varied

other (or unknown) substance use disorders. Often unknown substance use disorders will

be reclassified when the unknown substance eventually is identified.

Risk and Prognostic Factors

Risk and prognostic factors for other (or unknown) substance use disorders are thought to

be similar to those for most substance use disorders and include the presence of any other

substance use disorders, conduct disorder, or antisocial personality disorder in the individual or the individual's family; early onset of substance problems; easy availability of

the substance in the individual's environment; childhood maltreatment or trauma; and evidence of limited early self-control and behavioral disinhibition.

Cuiture-Reiated Diagnostic issues

Certain cultures may be associated with other (or unknown) substance use disorders involving specific indigenous substances within the cultural region, such as betel nut.

Diagnostic iViaricers

Urine, breath, or saliva tests may correctly identify a commonly used substance falsely

sold as a novel product. However, routine clinical tests usually cannot identify truly unusual or new substances, which may require testing in specialized laboratories.

Differential Diagnosis

Use of Other or unknown substances without meeting criteria for other (or unknown)

substance use disorder. Use of unknown substances is not rare among adolescents, but

most use does not meet the diagnostic standard of two or more criteria for other (or unknown) substance use disorder in the past year.

Substance use disorders. Other (or unknown) substance use disorder may co-occur

with various substance use disorders, and the symptoms of the disorders may be similar

and overlapping. To disentangle symptom patterns, it is helpful to inquire about which

symptoms persisted during periods when some of the substances were not being used.

Other (or unknown) substance/medication-induced disorder. This diagnosis should

be differentiated from instances when the individual's symptoms meet full criteria for one

of the following disorders, and that disorder is caused by an other or unknown substance:

delirium, major or mild neurocognitive disorder, psychotic disorder, depressive disorder,

anxiety disorder, sexual dysfunction, or sleep disorder.

Other medical conditions. Individuals with substance use disorders, including other

(or unknown) substance use disorder, may present with symptoms of many medical disorders. These disorders also may occur in the absence of other (or unknown) substance use

disorder. A history of little or no use of other or unknown substances helps to exclude

other (or unknown) substance use disorder as the source of these problems.

Comorbidity

Substance use disorders, including other (or unknown) substance use disorder, are commonly comorbid with one another, with adolescent conduct disorder and adult antisocial

personality disorder, and with suicidal ideation and suicide attempts.

Other (or Unknown) Substance Intoxication

------------------- ^______________________________________________________

Diagnostic Criteria

A. The development of a reversible substance-specific syndrome attributable to recent ingestion of (or exposure to) a substance that is not listed elsewhere or is unknown.

B. Clinically significant problematic behavioral or psychological changes that are attributable to the effect of the substance on the central nervous system (e.g., impaired motor

coordination, psychomotor agitation or retardation, euphoria, anxiety, belligerence,

mood lability, cognitive impairment, impaired judgment, social withdrawal) and develop

during, or shortly after, use of the substance.

C. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance.

Coding note: The ICD-9-CM code is 292.89. The ICD-10-CM code depends on whether

there is a comorbid other (or unknown) substance use disorder involving the same substance. If a mild other (or unknown) substance use disorder is comorbid, the ICD-10-CM

code is FI 9.129, and if a moderate or severe other (or unknown) substance use disorder is

comorbid, the ICD-10-CM code is FI 9.229. If there is no comorbid other (or unknown) substance use disorder involving the same substance, then the ICD-10-CM code is F19.929.

Note: For information on Risk and Prognostic Factors, Culture-Related Diagnostic Issues,

and Diagnostic Markers, see the corresponding sections in other (or unknown) substance

use disorder.

Diagnostic Features

Other (or unknown) substance intoxication is a clinically significant mental disorder that

develops during, or immediately after, use of either a) a substance not elsewhere addressed in this chapter (i.e., alcohol; caffeine; cannabis; phencyclidine and other hallucinogens; inhalants; opioids; sedatives, hypnotics, or anxiolytics; stimulants; or tobacco) or

b) an unknown substance. If the substance is known, it should be reflected in the name of

the disorder upon coding.

Application of the diagnostic criteria for other (or unknown) substance intoxication is

very challenging. Criterion A requires development of a reversible "substance-specific

syndrome," but if the substance is unknown, that syndrome usually will be unknown. To

resolve this conflict, clinicians may ask the individual or obtain collateral history as to

whether the individual has experienced a similar episode after using substances with the

same "street" name or from the same source. Similarly, hospital emergency departments

sometimes recognize over a few days numerous presentations of a severe, unfamiliar intoxication syndrome from a newly available, previously unknown substance. Because of

the great variety of intoxicating substances. Criterion B can provide only broad examples

of signs and symptoms from some intoxications, with no threshold for the number of

symptoms required for a diagnosis; clinical judgment guides those decisions. Criterion C

requires ruling out other medical conditions, mental disorders, or intoxications.

Prevalence

The prevalence of other (or unknown) substance intoxication is unknown.

Development and Course

Intoxications usually appear and then peak minutes to hours after use of the substance, but

the onset and course vary with the substance and the route of administration. Generally,

substances used by pulmonary inhalation and intravenous injection have the most rapid

onset of action, while those ingested by mouth and requiring metabolism to an active

product are much slower. (For example, after ingestion of certain mushrooms, the first

signs of an eventually fatal intoxication may not appear for a few days.) Intoxication effects usually resolve within hours to a very few days. However, the body may completely

eliminate an anesthetic gas such as nitrous oxide just minutes after use ends. At the other

extreme, some "hit-and-run" intoxicating substances poison systems, leaving permanent

impairments. For example, MPTP (l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine), a contaminating by-product in the synthesis of a certain opioid, kills dopaminergic cells and induces permanent parkinsonism in users who sought opioid intoxication.

Functional Consequences of

Other (or Unknown) Substance Intoxication

Impairment from intoxication with any substance may have serious consequences, including dysfunction at work, social indiscretions, problems in interpersonal relationships, failure to fulfill role obligations, traffic accidents, fighting, high-risk behaviors (i.e., having

unprotected sex), and substance or medication overdose. The pattern of consequences will

vary with the particular substance.

Differential Diagnosis

Use of Other or unknown substance, without meeting criteria for other (or unknown)

substance intoxication. The individual used an other or unknown substance(s), but the

dose was insufficient to produce symptoms that meet the diagnostic criteria required for

the diagnosis.

Substance intoxication or other substance/medication-induced disorders. Familiar substances may be sold in the black market as novel products, and individuals may experience

intoxication from those substances. History, toxicology screens, or chemical testing of the

substance itself may help to identify it.

Different types of other (or unknown) substance-related disorders. Episodes of other

(or unknown) substance intoxication may occur during, but are distinct from, other (or unknown) substance use disorder, unspecified other (or unknown) substance-related disorder, and other (or unknown) substance-induced disorders.

Other toxic, metabolic, traumatic, neoplastic, vascular, or infectious disorders that impair

brain function and cognition. Numerous neurological and other medical conditions may

produce rapid onset of signs and symptoms mimicking those of intoxications, including the

examples in Criterion B. Paradoxically, drug withdrawals also must be ruled out, because, for

example, lethargy may indicate withdrawal from one drug or intoxication with another drug.

Comorbidity

As with all substance-related disorders, adolescent conduct disorder, adult antisocial personality disorder, and other substance use disorders tend to co-occur with other (or unknown) substance intoxication.

Other (or Unknown) Substance Withdrawal

Diagnostic Criteria 292.0 (F19.239)

A. Cessation of (or reduction in) use of a substance that has been heavy and prolonged.

B. The development of a substance-specific syndrome shortly after the cessation of (or

reduction in) substance use.

C. The substance-specific syndrome causes clinically significant distress or impairment

in social, occupational, or other important areas of functioning.

D. The symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including withdrawal from another substance.

E. The substance involved cannot be classified under any of the other substance categories (alcohol; caffeine; cannabis; opioids; sedatives, hypnotics, or anxiolytics; stimulants; or tobacco) or is unknown.

Coding note: The ICD-9-CM code is 292.0. The ICD-10-CM code for other (or unknown) substance withdrawal is F19.239. Note that the ICD-10-CM code indicates the comorbid presence

of a moderate or severe other (or unknown) substance use disorder. It is not permissible to

code a comorbid mild other (or unknown) substance use disorder with other (or unknown) substance withdrawal.

Note: For information on Risk and Prognostic Factors and Diagnostic Markers, see the corresponding sections in other (or unknown) substance use disorder.

Diagnostic Features

Other (or unknown) substance withdrawal is a clinically significant mental disorder that

develops during, or within a few hours to days after, reducing or terminating dosing with

a substance (Criteria A and B). Although recent dose reduction or termination usually is

clear in the history, other diagnostic procedures are very challenging if the drug is unknown. Criterion B requires development of a "substance-specific syndrome" (i.e., the individual's signs and symptoms must correspond with the known withdrawal syndrome

for the recently stopped drug)—a requirement that rarely can be met with an unknown

substance. Consequently, clinical judgment must guide such decisions when information

is this limited. Criterion D requires ruling out other medical conditions, mental disorders,

or withdrawals from familiar substances. When the substance is known, it should be reflected in the name of the disorder upon coding (e.g., betel nut withdrawal).

Prevaience

The prevalence of other (or unknown) substance withdrawal is unknown.

Deveiopment and Course

Withdrawal signs commonly appear some hours after use of the substance is terminated,

but the onset and course vary greatly, depending on the dose typically used by the person

and the rate of elimination of the specific substance from the body. At peak severity, withdrawal symptoms from some substances involve only moderate levels of discomfort,

whereas withdrawal from other substances may be fatal. Withdrawal-associated dysphoria often motivates relapse to substance use. Withdrawal symptoms slowly abate over

days, weeks, or months, depending on the particular drug and doses to which the individual became tolerant.

Cuiture-Reiated Diagnostic issues

Culture-related issues in diagnosis will vary with the particular substance.

Functional Consequences of

Other (or Unknown) Substance Withdrawal

Withdrawal from any substance may have serious consequences, including physical signs

and symptoms (e.g., malaise, vital sign changes, abdominal distress, headache), intense

drug craving, anxiety, depression, agitation, psychotic symptoms, or cognitive impairments.

These consequences may lead to problems such as dysfunction at work, problems in interpersonal relationships, failure to fulfill role obligations, traffic accidents, fighting, highrisk behavior (e.g., having unprotected sex), suicide attempts, and substance or medication overdose. The pattern of consequences will vary with the particular substance.

Differential Diagnosis

Dose reduction after extended dosing, but not meeting the criteria for other (or unknown) substance withdrawal. The individual used other (or unknown) substances,

but the dose that was used was insufficient to produce symptoms that meet the criteria required for the diagnosis.

Substance withdrawal or other substance/medication-induced disorders. Familiar

substances may be sold in the black market as novel products, and individuals may experience withdrawal when discontinuing those substances. History, toxicology screens, or

chemical testing of the substance itself may help to identify it.

Different types of other (or unknown) substance-related disorders. Episodes of other

(or unknown) substance withdrawal may occur during, but are distinct from, other (or unknown) substance use disorder, unspecified other (or unknown) substance-related disorder, and unspecified other (or unknown) substance-induced disorders.

Other toxic, metabolic, traumatic, neoplastic, vascular, or infectious disorders that impair brain function and cognition. Numerous neurological and other medical conditions may produce rapid onset of signs and symptoms mimicking those of withdrawals.

Paradoxically, drug intoxications also must be ruled out, because, for example, lethargy

may indicate withdrawal from one drug or intoxication with another drug.

Comorbidity

As with all substance-related disorders, adolescent conduct disorder, adult antisocial personality disorder, and other substance use disorders likely co-occur with other (or unknown) substance withdrawal.

Other (or Unknown)

Substance-Induced Disorders

Because the category of other or unknown substances is inherently ill-defined, the extent

and range of induced disorders are uncertain. Nevertheless, other (or unknown) substance-induced disorders are possible and are described in other chapters of the manual

with disorders with which they share phenomenology (see the substance/medicationinduced mental disorders in these chapters): other (or unknown) substance-induced psychotic disorder ("Schizophrenia Spectrum and Other Psychotic Disorders"); other (or unknown substance-induced bipolar disorder ("Bipolar and Related Disorders"); other (or

unknown) substance-induced depressive disorder ("Depressive Disorders"); other (or

unknown) substance-induced anxiety disorders ("Anxiety Disorders"); other (or unknown) substance-induced obsessive-compulsive disorder ("Obsessive-Compulsive and

Related Disorders"); other (or unknown) substance-induced sleep disorder ("Sleep-Wake

Disorders"); other (or unknown) substance-induced sexual dysfunction ("Sexual Dysfunctions"); an(J other (or unknown) substance/medication-induced major or mild neurocognitive disorder ("Neurocognitive Disorders"). For other (or unknown) substanceinduced intoxication delirium and other (or unknown) substance-induced withdrawal

delirium, see the criteria and discussion of delirium in the chapter "Neurocognitive Disorders." These other (or unknown) substance-induced disorders are diagnosed instead of

other (or unknown) substance intoxication or other (or unknown) substance withdrawal

only when the symptoms are sufficiently severe to warrant independent clinical attention.

Unspecified Other (or Unknown)

Substance-Related Disorder

292.9 (F19.99)

This category applies to presentations in which symptoms characteristic of an other (or unknown) substance-related disorder that cause clinically significant distress or impairment

in social, occupational, or other important areas of functioning predominate but do not

meet the full criteria for any specific other (or unknown) substance-related disorder or any

of the disorders in the substance-related disorders diagnostic class.

Non-Substance-Related Disorders

Gambling Disorder

Diagnostic Criteria 312.31 (F63.0)

A. Persistent and recurrent problematic gambling behavior leading to clinically significant

impairment or distress, as indicated by the individual exhibiting four (or more) of the following in a 12-month period:

1. Needs to gamble with increasing amounts of money in order to achieve the desired

excitement.

2. Is restless or irritable when attempting to cut down or stop gambling.

3. Has made repeated unsuccessful efforts to control, cut back, or stop gambling.

4. Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past

gambling experiences, handicapping or planning the next venture, thinking of ways

to get money with which to gamble).

5. Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed).

6. After losing money gambling, often returns another day to get even (“chasing” one’s

losses).

7. Lies to conceal the extent of involvement with gambling.

8. Has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling.

9. Relies on others to provide money to relieve desperate financial situations caused

by gambling.

B. The gambling behavior is not better explained by a manic episode.

Specify if:

Episodic: Meeting diagnostic criteria at more than one time point, witli symptoms subsiding between periods of gambling disorder for at least several months.

Persistent: Experiencing continuous symptoms, to meet diagnostic criteria for multiple

years.

Specify if:

in eariy remission: After full criteria for gambling disorder were previously met, none

of the criteria for gambling disorder have been met for at least 3 months but for less

than 12 months.

in sustained remission: After full criteria for gambling disorder were previously met,

none of the criteria for gambling disorder have been met during a period of 12 months

or longer.

Specify current severity:

Mild: 4-5 criteria met.

iModerate: 6-7 criteria met.

Severe: 8-9 criteria met.

Note: Although some behavioral conditions that do not involve ingestion of substances

have similarities to substance-related disorders, only one disorder—gambling disorder—

has sufficient data to be included in this section.

Specifiers

Severity is based on the number of criteria endorsed. Individuals with mild gambling disorder may exhibit only 4-5 of the criteria, with the most frequently endorsed criteria usually related to preoccupation with gambling and "chasing" losses. Individuals with

moderately severe gambling disorder exhibit more of the criteria (i.e., 6-7). Individuals

with the most severe form will exhibit all or most of the nine criteria (i.e., 8-9). Jeopardizing relationships or career opportunities due to gambling and relying on others to provide

money for gambling losses are typically the least often endorsed criteria and most often occur among those with more severe gambling disorder. Furthermore, individuals presenting for treatment of gambling disorder typically have moderate to severe forms of the

disorder.

Diagnostic Features

Gambling involves risking something of value in the hopes of obtaining something of

greater value. In many cultures, individuals gamble on games and events, and most do so

without experiencing problems. However, some individuals develop substantial impairment related to their gambling behaviors. The essential feature of gambling disorder is

persistent and recurrent maladaptive gambling behavior that disrupts personal, family,

and/or vocational pursuits (Criterion A). Gambling disorder is defined as a cluster of four

or more of the symptoms listed in Criterion A occurring at any time in the same 12-month

period.

A pattern of "chasing one's losses" may develop, with an urgent need to keep gambling (often with the placing of larger bets or the taking of greater risks) to undo a loss or

series of losses. The individual may abandon his or her gambling strategy and try to win

back losses all at once. Although many gamblers may "chase" for short periods of time, it

is the frequent, and often long-term, "chase" that is characteristic of gambling disorder

(Criterion A6). Individuals may lie to family members, therapists, or others to conceal the

extent of involvement with gambling; these instances of deceit may also include, but

are not limited to, covering up illegal behaviors such as forgery, fraud, theft, or embezzlement to obtain money with which to gamble (Criterion A7). Individuals may also en-

gage in "bailout" behavior, turning to family or others for help with a desperate financial

situation that w,as caused by gambling (Criterion A9).

Associated Features Supporting Diagnosis

Distortions in thinking (e.g., denial, superstitions, a sense of power and control over the

outcome of chance events, overconfidence) may be present in individuals with gambling

disorder. Many individuals with gambling disorder believe that money is both the cause

of and the solution to their problems. Some individuals with gambling disorder are impulsive, competitive, energetic, restless, and easily bored; they may be overly concerned

with the approval of others and may be generous to the point of extravagance when winning. Other individuals with gambling disorder are depressed and lonely, and they may

gamble when feeling helpless, guilty, or depressed. Up to half of individuals in treatment

for gambling disorder have suicidal ideation, and about 17% have attempted suicide.

Prevaience

The past-year prevalence rate of gambling disorder is about 0.2%-0.3% in the general population. In the general population, the lifetime prevalence rate is about 0.4%-1.0%. For females, the lifetime prevalence rate of gambling disorder is about 0.2%, and for males it is

about 0.6%. The lifetime prevalence of pathological gambling among African Americans is

about 0.9%, among whites about 0.4%, and among Hispanics about 0.3%.

Deveiopment and Course

The onset of gambling disorder can occur during adolescence or young adulthood, but in

other individuals it manifests during middle or even older adulthood. Generally, gambling disorder develops over the course of years, although the progression appears to be

more rapid in females than in males. Most individuals who develop a gambling disorder

evidence a pattern of gambling that gradually increases in both frequency and amount of

wagering. Certainly, milder forms can develop into more severe cases. Most individuals

with gambling disorder report that one or two types of gambling are most problematic for

them, although some individuals participate in many forms of gambling. Individuals are

likely to engage in certain types of gambling (e.g., buying scratch tickets daily) more frequently than others (e.g., playing slot machines or blackjack at the casino weekly). Frequency of gambling can be related more to the type of gambling than to the severity of the

overall gambling disorder. For example, purchasing a single scratch ticket each day may

not be problematic, while less frequent casino, sports, or card gambling may be part of a

gambling disorder. Similarly, amounts of money spent wagering are not in themselves indicative of gambling disorder. Some individuals can wager thousands of dollars per

month and not have a problem with gambling, while others may wager much smaller

amounts but experience substantial gambling-related difficulties.

Gambling patterns may be regular or episodic, and gambling disorder can be persistent or in remission. Gambling can increase during periods of stress or depression and

during periods of substance use or abstinence. There may be periods of heavy gambling

and severe problems, times of total abstinence, and periods of nonproblematic gambling.

Gambling disorder is sometimes associated with spontaneous, long-term remissions.

Nevertheless, some individuals underestimate their vulnerability to develop gambling

disorder or to return to gambling disorder following remission. When in a period of remission, they may incorrectly assume that they will have no problem regulating gambling

and that they may gamble on some forms nonproblematically, only to experience a return

to gambling disorder.

Early expression of gambling disorder is more common among males than among females. Individuals who begin gambling in youth often do so with family members or

friends. Development of early-life gambling disorder appears to be associated v^ith impulsivity and substance abuse. Many high school and college shidents who develop gambling

disorder grow out of the disorder over time, although it remains a lifelong problem for

some. Mid- and later-life onset of gambling disorder is more common among females than

among males.

There are age and gender variations in the type of gambling activities and the prevalence rates of gambling disorder. Gambling disorder is more common among younger and

middle-age persons than among older adults. Among adolescents and young adults, the

disorder is more prevalent in males than in females. Younger individuals prefer different

forms of gambling (e.g., sports betting), while older adults are more likely to develop

problems with slot machine and bingo gambling. Although the proportions of individuals

who seek treatment for gambling disorder are low across all age groups, younger individuals are especially unlikely to present for treatment.

Males are more likely to begin gambling earlier in life and to have a younger age at onset of gambling disorder than females, who are more likely to begin gambling later in life

and to develop gambling disorder in a shorter time frame. Females with gambling disorder are more likely than males with gambling disorder to have depressive, bipolar, and

anxiety disorders. Females also have a later age at onset of the disorder and seek treatment

sooner, although rates of treatment seeking are low (<10%) among individuals with gambling disorder regardless of gender.

Risk and Prognostic Factors

Temperamental. Gambling that begins in childhood or early adolescence is associated

with increased rates of gambling disorder. Gambling disorder also appears to aggregate

with antisocial personality disorder, depressive and bipolar disorders, and other substance use disorders, particularly with alcohol disorders.

Genetic and physiological. Gambling disorder can aggregate in families, and this effect

appears to relate to both environmental and genetic factors. Gambling problems are more

frequent in monozygotic than in dizygotic twins. Gambling disorder is also more prevalent among first-degree relatives of individuals with moderate to severe alcohol use disorder than among the general population.

Course modifiers. Many individuals, including adolescents and young adults, are likely to

resolve their problems with gambling disorder over time, although a strong predictor of

future gambling problems is prior gambling problems.

Culture-Related Diagnostic issues

Individuals from specific cultures and races/ethnicities are more likely to participate in

some types of gambling activities than others (e.g., pai gow, cockfights, blackjack, horse racing). Prevalence rates of gambling disorder are higher among African Americans than

among European Americans, with rates for Hispanic Americans similar to those of European Americans. Indigenous populations have high prevalence rates of gambling disorder.

Gender-Related Diagnostic issues

Males develop gambling disorder at higher rates than females, although this gender gap

may be narrowing. Males tend to wager on different forms of gambling than females, with

cards, sports, and horse race gambling more prevalent among males, and slot machine and

bingo gambling more common among females.

Functional Consequences of Gambling Disorder

Areas of psychosocial, health, and mental health functioning may be adversely affected by

gambling disorder. Specifically, individuals with gambling disorder may, because of their

involvement with gambling, jeopardize or lose important relationships with family members or friends. Such problems may occur from repeatedly lying to others to cover up the

extent of gambling or from requesting money that is used for gambling or to pay off gambling debts. Employment or educational activities may likewise be adversely impacted by

gambling disorder; absenteeism or poor work or school performance can occur with gambling disorder, as individuals may gamble during work or school hours or be preoccupied

with gambling or its adverse consequence when they should be working or studying. Individuals with gambling disorder have poor general health and utilize medical services at

high rates.

Differential Diagnosis

Nondisordered gambling. Gambling disorder must be distinguished from professional

and social gambling. In professional gambling, risks are limited and discipline is central.

Social gambling typically occurs with friends or colleagues and lasts for a limited period of

time, with acceptable losses. Some individuals can experience problems associated with

gambling (e.g., short-term chasing behavior and loss of control) that do not meet the full

criteria for gambling disorder.

Manic episode. Loss of judgment and excessive gambling may occur during a manic episode. An additional diagnosis of gambling disorder should be given only if the gambling

behavior is not better explained by manic episodes (e.g., a history of maladaptive gambling behavior at times other than during a manic episode). Alternatively, an individual

with gambling disorder may, during a period of gambling, exhibit behavior that resembles

a manic episode, but once the individual is away from the gambling, these manic-like features dissipate.

Personality disorders. Problems with gambling may occur in individuals with antisocial

personality disorder and other personality disorders. If the criteria are met for both disorders, both can be diagnosed.

Other medical conditions. Some patients taking dopaminergic medications (e.g., for

Parkinson's disease) may experience urges to gamble. If such symptoms dissipate when

dopaminergic medications are reduced in dosage or ceased, then a diagnosis of gambling

disorder would not be indicated.

Comorbidity

Gambling disorder is associated with poor general health. In addition, some specific medical diagnoses, such as tachycardia and angina, are more common among individuals with

gambling disorder than in the general population, even when other substance use disorders, including tobacco use disorder, are controlled for. Individuals with gambling disorder have high rates of comorbidity with other mental disorders, such as substance use

disorders, depressive disorders, anxiety disorders, and personality disorders. In some individuals, other mental disorders may precede gambling disorder and be either absent or

present during the manifestation of gambling disorder. Gambling disorder may also occur

prior to the onset of other mental disorders, especially anxiety disorders and substance use

disorders.

The neurocognitive disorders (NCDs) (referred to in DSM-IV as "Dementia,

Delirium, Amnestic, and Other Cognitive Disorders") begin with delirium, followed by

the syndromes of major NCD, mild NCD, and their etiological subtypes. The major or

mild NCD subtypes are NCD due to Alzheimer's disease; vascular NCD; NCD with Lewy

bodies; NCD due to Parkinson's disease; frontotemporal NCD; NCD due to traumatic

brain injury; NCD due to HIV infection; substance/medication-induced NCD; NCD due

to Huntington's disease; NCD due to prion disease; NCD due to another medical condition; NCD due to multiple etiologies; and unspecified NCD. The NCD category encompasses the group of disorders in which the primary clinical deficit is in cognitive function,

and that are acquired rather than developmental. Although cognitive deficits are present

in many if not all mental disorders (e.g., schizophrenia, bipolar disorders), only disorders

whose core features are cognitive are included in the NCD category. The NCDs are those

in which impaired cognition has not been present since birth or very early life, and thus

represents a decline from a previously attained level of functioning.

The NCDs are unique among DSM-5 categories in that these are syndromes for which

the underlying pathology, and frequently the etiology as well, can potentially be determined. The various underlying disease entities have all been the subject of extensive research, clinical experience, and expert consensus on diagnostic criteria. The DSM-5 criteria

for these disorders have been developed in close consultation with the expert groups for

each of the disease entities and align as closely as possible with the current consensus criteria for each of them. The potential utility of biomarkers is also discussed in relation to

diagnosis. Dementia is subsumed imder the newly named entity major neurocognitive disorder, although the term dementia is not precluded from use in the etiological subtypes in

which that term is standard. Furthermore, DSM-5 recognizes a less severe level of cognitive impairment, mild neurocognitive disorder, which can also be a focus of care, and which

in DSM-IV was subsumed under "Cognitive Disorder Not Otherwise Specified." Diagnostic criteria are provided for both these syndromic entities, followed by diagnostic criteria

for the different etiological subtypes. Several of the NCDs frequently coexist with one another, and their relationships may be multiply characterized under different chapter subheadings, including "Differential Diagnosis" (e.g., NCD due to Alzheimer's disease vs.

vascular NCD), "Risk and Prognostic Factors" (e.g., vascular pathology increasing the

clinical expression of Alzheimer's disease), and/or "Comorbidity" (e.g., mixed Alzheimer's disease-vascular pathology).

The term dementia is retained in DSM-5 for continuity and may be used in settings

where physicians and patients are accustomed to this term. Although dementia is the customary term for disorders like the degenerative dementias that usually affect older adults,

the term neurocognitive disorder is widely used and often preferred for conditions affecting younger individuals, such as impairment secondary to traumatic brain injury or HIV

infection. Furthermore, the major NCD definition is somewhat broader than the term

dementia, in that individuals with substantial decline in a single domain can receive this diagnosis, most notably the DSM-IV category of "Amnestic Disorder," which would now be

diagnosed as major NCD due to another medical condition and for which the term dementia would not be used.

Neurocognitive Domains

The criteria for the various NCDs are all based on defined cognitive domains. Table 1 provides for each of the key domains a working definition, examples of symptoms or observations regarding impairments in everyday activities, and examples of assessments. The

domains thus defined, along with guidelines for clinical thresholds, form the basis on

which the NCDs, their levels, and their subtypes may be diagnosed.

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Delirium

Diagnostic Criteria

A.

B.

A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment).

The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.

C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language,

visuospatial ability, or perception).

D. The disturbances in Criteria A and C are not better explained by another preexisting,

established, or evolving neurocognitive disorder and do not occur in the context of a

severely reduced level of arousal, such as coma.

E. There is evidence from the history, physical examination, or laboratory findings that the

disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or

exposure to a toxin, or is due to multiple etiologies.

Specify whether:

Substance intoxication delirium: This diagnosis should be made instead of substance intoxication when the symptoms in Criteria A and C predominate in the clinical

picture and when they are sufficiently severe to warrant clinical attention.

Coding note: The ICD-9-CM and ICD-10-CM codes for the [specific substance] intoxication delirium are indicated in the table below. Note that the ICD-10-CM code

depends on whether or not there is a comorbid substance use disorder present for

the same class of substance. If a mild substance use disorder is comorbid with the

substance intoxication delirium, the 4th position character is “1,” and the clinician

should record “mild [substance] use disorder” before the substance intoxication delirium (e.g., “mild cocaine use disorder with cocaine intoxication delirium”). If a moderate or severe substance use disorder is comorbid with the substance intoxication

delirium, the 4th position character is “2,” and the clinician should record “moderate

[substance] use disorder” or “severe [substance] use disorder,” depending on the

severity of the comorbid substance use disorder. If there is no comorbid substance

use disorder (e.g., after a one-time heavy use of the substance), then the 4th position character is “9,” and the clinician should record only the substance intoxication

delirium.

ICD-10-CM

ICD-9-CM

With use

disorder,

mild

With use

disorder,

moderate or

severe

Without use

disorder

Alcohol 291.0 F10.121 F10.221 FI 0.921

Cannabis 292.81 F12.121 F12.221 F12.921

Phencyclidine 292.81 F16.121 FI 6.221 FI 6.921

Other hallucinogen 292.81 F16.121 FI 6.221 FI 6.921

Inhalant 292.81 F18.121 F18.221 FI 8.921

Opioid 292.81 F11.121 F11.221 F11.921

ICD-10-CM

ICD-9-CM

With use

disorder,

mild

With use

disorder,

moderate or

severe

Without use

disorder

Sedative, hypnotic, or anxiolytic 292.81 F13.121 F13.221 FI 3.921

Amphetamine (or other

stimulant)

292.81 F15.121 F15.221 F15.921

Cocaine 292.81 F14.121 FI 4.221 F14.921

Other (or unknown) substance 292.81 F19.121 F19.221 FI 9.921

Substance withdrawal delirium: Tliis diagnosis should be made instead of substance withdrawal when the symptoms in Criteria A and C predominate in the clinical

picture and when they are sufficiently severe to warrant clinical attention.

Code [specific substance] withdrawal delirium: 291.0 (F I0.231) alcohol; 292.0

(F11.23) opioid: 292.0 (F I3.231) sedative, hypnotic, or anxiolytic; 292.0 (F19.231)

other (or unknown) substance/medication.

Medication-induced delirium: This diagnosis applies when the symptoms in Criteria

A and C arise as a side effect of a medication taken as prescribed.

Coding note: The ICD-9-CM code for [specific medication]-induced delirium is

292.81. The ICD-10-CM code depends on the type of medication. If the medication

is an opioid taken as prescribed, the code is F11.921. If the medication is a sedative, hypnotic, or anxiolytic taken as prescribed, the code is FI 3.921. If the medication is an amphetamine-type or other stimulant taken as prescribed, the code is

F I5.921. For medications that do not fit into any of the classes (e.g., dexamethasone) and in cases in which a substance is judged to be an etiological factor but the

specific class of substance is unknown, the code is F19.921.

293.0 (F05) Delirium due to another medical condition: There is evidence from the

history, physical examination, or laboratory findings that the disturbance is attributable

to the physiological consequences of another medical condition.

Coding note: Include the name of the other medical condition in the name of the

delirium (e.g., 293.0 [F05] delirium due to hepatic encephalopathy). The other medical condition should also be coded and listed separately immediately before the

delirium due to another medical condition (e.g., 572.2 [K72.90] hepatic encephalopathy; 293.0 [F05] delirium due to hepatic encephalopathy).

293.0 (F05) Delirium due to multiple etiologies: There is evidence from the history,

physical examination, or laboratory findings that the delirium has more than one etiology (e.g., more than one etiological medical condition; another medical condition plus

substance intoxication or medication side effect).

Coding note: Use multiple separate codes reflecting specific delirium etiologies

(e.g., 572.2 [K72.90] hepatic encephalopathy, 293.0 [F05] delirium due to hepatic

failure; 291.0 [FI 0.231] alcohol withdrawal delirium). Note that the etiological medical condition both appears as a separate code that precedes the delirium code and

is substituted into the delirium due to another medical condition rubric.

Specify if:

Acute: Lasting a few hours or days.

Persistent: Lasting weeks or months.

Specify if:

Hyperactive: The individual has a hyperactive level of psychomotor activity that may be

accompanied by mood lability, agitation, and/or refusal to cooperate with medical care.

Hypoactive: The individual has a hypoactive level of psychomotor activity that may be

accompanied by sluggishness and lethargy that approaches stupor.

Mixed level of activity; The individual has a normal level of psychomotor activity even

though attention and awareness are disturbed. Also includes individuals whose activity

level rapidly fluctuates.

Recording Procedures

Substance intoxication delirium

ICD-9-CM, The name of the substance/medication intoxication delirium begins with

the specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing the

delirium. The diagnostic code is selected from the table included in the criteria set, which

is based on the drug class. For substances that do not fit into any of the classes (e.g., dexamethasone), the code for "other substance" should be used; and in cases in which a substance is judged to be an etiological factor but the specific class of substance is unknown,

the category "unknown substance" should be used.

The name of the disorder is followed by the course (i.e., acute, persistent), followed by

the specifier indicating level of psychomotor activity (i.e., hyperactive, hypoactive, mixed

level of activity). Unlike the recording procedures for ICD-IO-CM, which combine the substance/medication intoxication delirium and substance use disorder into a single code, for

ICD-9-CM a separate diagnostic code is given for the substance use disorder. For example,

in the case of acute hyperactive intoxication delirium occurring in a man with a severe cocaine use disorder, the diagnosis is 292.81 cocaine intoxication delirium, acute, hyperactive. An additional diagnosis of 304.20 severe cocaine use disorder is also given. If the

intoxication delirium occurs without a comorbid substance use disorder (e.g., after a onetime heavy use of the substance), no accompanying substance use disorder is noted (e.g.,

292.81 phencyclidine intoxication delirium, acute, hypoactive).

ICD-IO-CM. The name of the substance/medication intoxication delirium begins with the

specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing the delirium.

The diagnostic code is selected from the table included in the criteria set, which is based on the

drug class and presence or absence of a comorbid substance use disorder. For substances that

do not fit into any of the classes (e.g., dexamethasone), the code for "other substance" should

be used; and in cases in which a substance is judged to be an etiological factor but the specific

class of substance is unknown, the category "unknown substance" should be used.

When recording the name of the disorder, the comorbid substance use disorder (if any) is

listed first, followed by the word "with," followed by the name of the substance intoxication

delirium, followed by the course (i.e., acute, persistent), followed by the specifier indicating

level of psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity). For example, in the case of acute hyperactive intoxication delirium occurring in a man with a severe cocaine use disorder, the diagnosis is F14.221 severe cocaine use disorder with cocaine

intoxication delirium, acute, hyperactive. A separate diagnosis of the comorbid severe cocaine

use disorder is not given. If the intoxication delirium occurs without a comorbid substance use

disorder (e.g., after a one-time heavy use of the substance), no accompanying substance use

disorder is noted (e.g., F16.921 phencyclidine intoxication delirium, acute, hypoactive).

Substance withdrawal delirium

ICD-9~CM, The name of the substance/medication withdrawal delirium begins with the

specific substance (e.g., alcohol) that is presumed to be causing the withdrawal delirium. The

diagnostic code is selected from substance-specific codes included in the coding note included

in the criteria set. The name of the disorder is followed by the course (i.e., acute, persistent), followed by the specifier indicating level of psychomotor activity (i.e., hyperactive, hypoactive,

mixed level of activity). Unlike the recording procedures for ICD-IO-CM, which combine the

substance/medication withdrawal delirium and substance use disorder into a single code, for

ICD-9-CM a separate diagnostic code is given for the substance use disorder. For example, in

the case of acute h3φeractive withdrawal delirium occurring in a man with a severe alcohol use

disorder, the diagnosis is 291.0 alcohol withdrawal delirium, acute, hyperactive. An additional

diagnosis of 303.90 severe alcohol use disorder is also given.

ICD-10~CM. The name of the substance/medication withdrawal delirium begins with

the specific substance (e.g., alcohol) that is presumed to be causing the withdrawal delirium. The diagnostic code is selected from substance-specific codes included in the coding

note included in the criteria set. When recording the name of the disorder, the comorbid

moderate or severe substance use disorder (if any) is listed first, followed by the word

"with," followed by the substance withdrawal delirium, followed by the course (i.e., acute,

persistent), followed by the specifier indicating level of psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity). For example, in the case of acute hyperactive

withdrawal delirium occurring in a man with a severe alcohol use disorder, the diagnosis

is F10.231 severe alcohol use disorder with alcohol withdrawal delirium, acute, hyperactive. A separate diagnosis of the comorbid severe alcohol use disorder is not given.

Medication-induced delirium. The name of the medication-induced delirium begins

with the specific substance (e.g., dexamethasone) that is presumed to be causing the delirium. The name of the disorder is followed by the course (i.e., acute, persistent), followed

by the specifier indicating level of psychomotor activity (i.e., hyperactive, hypoactive,

mixed level of activity). For example, in the case of acute hyperactive medication-induced

delirium occurring in a man using dexamethasone as prescribed, the diagnosis is 292.81

(F19.921) dexamethasone-induced delirium, acute, hyperactive.

Specifiers

Regarding course, in hospital settings, delirium usually lasts about 1 week, but some

symptoms often persist even after individuals are discharged from the hospital.

Individuals with delirium may rapidly switch between hyperactive and hypoactive

states. The hyperactive state may be more common or more frequently recognized and

often is associated with medication side effects and drug withdrawal. The hypoactive state

may be more frequent in older adults.

Diagnostic Features

The essential feature of delirium is a disturbance of attention or awareness that is accompanied by a change in baseline cognition that cannot be better explained by a preexisting

or evolving neurocognitive disorder (NCD). The disturbance in attention (Criterion A) is

manifested by reduced ability to direct, focus, sustain, and shift attention. Questions must

be repeated because the individual's attention wanders, or the individual may perseverate

with an answer to a previous question rather than appropriately shift attention. The individual is easily distracted by irrelevant stimuli. The disturbance in awareness is manifested by a reduced orientation to the environment or at times even to oneself.

The disturbance develops over a short period of time, usually hours to a few days, and

tends to fluctuate during the course of the day, often with worsening in the evening and

night when external orienting stimuli decrease (Criterion B). There is evidence from the

history, physical examination, or laboratory findings that the disturbance is a physiological consequence of an underlying medical condition, substance intoxication or withdrawal, use of a medication, or a toxin exposure, or a combination of these factors

(Criterion E). The etiology should be coded according to the etiologically appropriate subtype (i.e., substance or medication intoxication, substance withdrawal, another medical

condition, or multiple etiologies). Delirium often occurs in the context of an underlying

NCD. The impaired brain function of individuals with mild and major NCD renders them

more vulnerable to delirium.

There is an accompanying change in at least one other area that may include memory

and learning (particularly recent memory), disorientation (particularly to time and place),

alteration in language, or perceptual distortion or a perceptual-motor disturbance (Criterion C). The perceptual disturbances accompanying delirium include misinterpretations,

illusions, or hallucinations; these disturbances are typically visual, but may occur in other

modalities as well, and range from simple and uniform to highly complex. Normal attention/arousal, delirium, and coma lie on a continuum, with coma defined as the lack of any

response to verbal stimuli. The ability to evaluate cognition to diagnose delirium depends

on there being a level of arousal sufficient for response to verbal stimulation; hence, delirium should not be diagnosed in the context of coma (Criterion D). Many noncoma tose patients have a reduced level of arousal. Those patients who show only minimal responses to

verbal stimulation are incapable of engaging with attempts at standardized testing or even

interview. This inability to engage should be classified as severe inattention. Low-arousal

states (of acute onset) should be recognized as indicating severe inattention and cognitive

change, and hence delirium. They are clinically indistinguishable from delirium diagnosed on the basis of inattention or cognitive change elicited through cognitive testing and

interview.

Associated Features Supporting Diagnosis

Delirium is often associated with a disturbance in the sleep-wake cycle. This disturbance

can include daytime sleepiness, nighttime agitation, difficulty falling asleep, excessive

sleepiness throughout the day, or wakefulness throughout the night. In some cases, complete reversal of the night-day sleep-wake cycle can occur. Sleep-wake cycle disturbances

are very common in delirium and have been proposed as a core criterion for the diagnosis.

The individual with delirium may exhibit emotional disturbances, such as anxiety,

fear, depression, irritability, anger, euphoria, and apathy. There may be rapid and unpredictable shifts from one emotional state to another. The disturbed emotional state may also

be evident in calling out, screaming, cursing, muttering, moaning, or making other

sounds. These behaviors are especially prevalent at night and under conditions in which

stimulation and environmental cues are lacking.

Prevaience

The prevalence of delirium is highest among hospitalized older individuals and varies

depending on the individuals' characteristics, setting of care, and sensitivity of the detection method. The prevalence of delirium in the community overall is low (l%-2%) but increases with age, rising to 14% among individuals older than 85 years. The prevalence is

10%-30% in older individuals presenting to emergency departments, where the delirium

often indicates a medical illness.

The prevalence of delirium when individuals are admitted to the hospital ranges from

14% to 24%, and estimates of the incidence of delirium arising during hospitalization

range from 6% to 56% in general hospital populations. Delirium occurs in 15%-53% of

older individuals postoperatively and in 70%-87% of those in intensive care. Delirium occurs in up to 60% of individuals in nursing homes or post-acute care settings and in up to

83% of all individuals at the end of life.

Development and Course

While the majority of individuals with delirium have a full recovery with or without

treatment, early recognition and intervention usually shortens the duration of the delir-

ium. Delirium may progress to stupor, coma, seizures, or death, particularly if the underlying cause remains untreated. Mortality among hospitalized individuals with delirium is

high, and as many as 40% of individuals with delirium, particularly those with malignancies and other significant underlying medical illness, die within a year after diagnosis.

Risk and Prognostic Factors

Environmental. Delirium may be increased in the context of functional impairment, immobility, a history of falls, low levels of activity, and use of drugs and medications with

psychoactive properties (particularly alcohol and anticholinergics).

Genetic and physiological. Both major and mild NCDs can increase the risk for delirium and complicate the course. Older individuals are especially susceptible to delirium

compared with younger adults. Susceptibility to delirium in infancy and through childhood may be greater than in early and middle adulthood. In childhood, delirium may be

related to febrile illnesses and certain medications (e.g., anticholinergics).

Diagnostic iVlaricers

In addition to laboratory findings characteristic of underlying medical conditions (or intoxication or withdrawal states), there is often generalized slowing on electroencephalography, and fast activity is occasionally found (e.g., in some cases of alcohol withdrawal

delirium). However, electroencephalography is insufficiently sensitive and specific for diagnostic use.

Functional Consequences of Deiirium

Delirium itself is associated with increased functional decline and risk of institutional

placement. Hospitalized individuals 65 years or older with delirium have three times the

risk of nursing home placement and about three times the functional decline as hospitalized patients without delirium at both discharge and 3 months postdischarge.

Differential Diagnosis

Psychotic disorders and bipolar and depressive disorders with psychotic features.

Delirium that is characterized by vivid hallucinations, delusions, language disturbances,

and agitation must be distinguished from brief psychotic disorder, schizophrenia, schizophreniform disorder, and other psychotic disorders, as well as from bipolar and depressive disorders with psychotic features.

Acute stress disorder. Delirium associated with fear, anxiety, and dissociative symptoms,

such as depersonalization, must be distinguished from acute stress disorder, which is precipitated by exposure to a severely traumatic event.

Malingering and factitious disorder. Delirium can be distinguished from these disorders on the basis of the often atypical presentation in malingering and factitious disorder

and the absence of another medical condition or substance that is etiologically related to

the apparent cognitive disturbance.

Other neurocognitive disorders. The most common differential diagnostic issue when

evaluating confusion in older adults is disentangling symptoms of delirium and dementia.

The clinician must determine whether the individual has delirium; a delirium superimposed on a preexisting NCD, such as that due to Alzheimer's disease; or an NCD without

delirium. The traditional distinction between delirium and dementia according to acuteness of onset and temporal course is particularly difficult in those elderly individuals who

had a prior NCD that may not have been recognized, or who develop persistent cognitive

impairment following an episode of delirium.

Other Specified Delirium

780.09 (R41.0)

This category applies to presentations in which symptoms characteristic of delirium that

cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria for delirium or any of

the disorders in the neurocognitive disorders diagnostic class. The other specified delirium

category is used in situations in which the clinician chooses to communicate the specific

reason that the presentation does not meet the criteria for delirium or any specific neurocognitive disorder. This is done by recording “other specified delirium” followed by the specific reason (e.g., “attenuated delirium syndrome”).

An example of a presentation that can be specified using the “other specified” designation is the following:

Attenuated delirium syndrome: This syndrome applies in cases of delirium in which

the severity of cognitive impairment falls short of that required for the diagnosis, or in

which some, but not all, diagnostic criteria for delirium are met.

Unspecified Delirium

780.09 (R41.0)

This category applies to presentations in which symptoms characteristic of delirium that

cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria for delirium or any of

the disorders in the neurocognitive disorders diagnostic class. The unspecified delirium

category is used in situations in which the clinician chooses not to specify the reason that

the criteria are not met for delirium, and includes presentations for which there is insufficient information to make a more specific diagnosis (e.g., in emergency room settings).

Major and Mild Neurocognitive Disorders

Major Neurocognitive Disorder

Diagnostic Criteria

A. Evidence of significant cognitive decline from a previous level of performance in one

or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) based on:

1. Concern of the individual, a knowledgeable informant, or the clinician that there has

been a significant decline in cognitive function; and

2. A substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical

assessment.

B. The cognitive deficits interfere with independence in everyday activities (i.e., at a minimum, requiring assistance with complex instrumental activities of daily living such as

paying bills or managing medications).

C. The cognitive deficits do not occur exclusively in the context of a delirium.

D. The cognitive deficits are not better explained by another mental disorder (e.g., major

depressive disorder, schizophrenia).

Specify whether due to:

Alzheimer’s disease (pp. 611-614)

Frontotemporal lobar degeneration (pp. 614-618)

Lewy body disease (pp. 618-621)

Vascular disease (pp. 621-624)

Traumatic brain injury (pp. 624-627)

Substance/medication use (pp. 627-632)

HIV infection (pp. 632-634)

Prion disease (pp. 634-636)

Parkinson’s disease (pp. 636-638)

Huntington’s disease (pp. 638-641)

Anotlier medical condition (pp. 641-642)

Multiple etiologies (pp. 642-643)

Unspecified (p. 643)

Coding note: Code based on medical or substance etiology. In some cases, there Is need

for an additional code for the etiological medical condition, which must immediately precede the diagnostic code for major neurocognitive disorder, as follows:

Associated etiological

medical code for major Major neurocogni- Mild neurocogniEtiological subtype neurocognitive disorder® tive disorder code^ tive disorder code®

Alzheimer’s Probable: 331.0 (G30.9) Probable: 294.1x 331.83 (G31.84)

disease Possible: no additional (F02.8X) (Do not use addimedical code Possible: 331.9 tional code for

(G31.9)‘= Alzheimer’s

disease.)

Frontotemporal Probable: 331.19 Probable: 294.1x 331.83(031.84)

lobar degeneration (G31.09) (F02.8X) (Do not use addiPossible: no additional Possible: 331.9 tional code for

medical code (031.9)*= frontotemporal

disease.)

Lewy body disease Probable: 331.82 Probable: 294.1x 331.83(031.84)

(G31.83) (F02.8X) (Do not use addiPossible: no additional Possible: 331.9 tional code for

medical code (031.9)*= Lewy body disease.)

Vascular disease No additional medical Probable: 290.40 331.83 (031.84)

code (F01.5X) (Do not use addiPossible: 331.9 tional code for the

(G31.9 f vascular disease.)

Traumatic brain 907.0 (S06.2X9S) 294.1x (F02.8X) 331.83 (031.84)

injury (Do not use additional

code for the traumatic brain injury.)

Substance/ No additional medical Code based on the Code based on the

medication- code type of substance type of substance

induced causing the major causing the mild

neurocognitive neurocognitive

disorder‘d’ disorder^

Associated etiological

medical code for major Major neurocogni- Mild neurocogniEtiological subtype neurocognitive disorder^ tive disorder code^ tive disorder code^

HIV infection 042 (B20) 294.1x(F02.8x) 331.83 (G31.84)

(Do not use additional code for HIV

infection.)

Prion disease 046.79 (A81.9) 294.1x (F02.8X) 331.83 (G31.84)

(Do not use additional code for

prion disease.)

Parkinson’s

disease

Probable: 332.0 (G20)

Possible: No additional

medical code

Probable: 294.1x

(F02.8X)

Possible: 331.9

(G31.9)''

331.83 (G31.84)

(Do not use additional code for

Parkinson’s

disease.)

Huntington’s

disease

333.4 (G10) 294.1x (F02.8X) 331.83 (G31.84)

(Do not use additional code for

Huntington’s

disease.)

Due to another

medical condition

Code the other medical

condition first

(e.g., 340 [G35]

multiple sclerosis)

294.1x (F02.8X) 331.83 (G31.84)

(Do not use additional codes for the

presumed etiological medical conditions.)

Due to multiple

etiologies

Code all of the etiological

medical conditions first

(with the exception of

vascular disease)

294.1x (F02.8X)

(Plus the code for

the relevant substance/medicationinduced major neurocognitive disorders if substances

or medications

play a role in the

etiology.)

331.83 (G31.84)

(Plus the code for

the relevant substance/medicationinduced mild neurocognitive disorders if substances

or medications play

a role in the etiology. Do not use additional codes for

the presumed

etiological medical

conditions.)

Unspecified neurocognitive disorder

No additional medical

code

799.59 (R41.9) 799.59 (R41.9)

^Code first, before code for major neurocognitive disorder.

^Code fifth character based on symptom specifier: .xO without behavioral disturbance; .xl with behavioral disturbance (e.g., psychotic symptoms, mood disturbance, agitation, apathy, or other behavioral symptoms).

^Note: Behavioral disturbance specifier cannot be coded but should still be indicated in writing.

^See "'Substance/Medication-Induced Major or Mild Neurocognitive Disorder."

Specify:

Without behjavioral disturbance: If the cognitive disturbance is not accompanied by

any clinically significant behavioral disturbance.

With behavioral disturbance (specify disturbance): If the cognitive disturbance is accompanied by a clinically significant behavioral disturbance (e.g., psychotic symptoms,

mood disturbance, agitation, apathy, or other behavioral symptoms).

Specify current severity:

iUlild: Difficulties with instrumental activities of daily living (e.g., housework, managing

money).

Moderate: Difficulties with basic activities of daily living (e.g., feeding, dressing).

Severe: Fully dependent.

ild Neurocognitive Disorder

Diagnostic Criteria

A. Evidence of modest cognitive decline from a previous level of performance in one or

more cognitive domains (complex attention, executive function, learning and memory,

language, perceptual motor, or social cognition) based on:

1. Concern of the individual, a knowledgeable informant, or the clinician that there has

been a mild decline in cognitive function; and

2. A modest impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical

assessment.

B. The cognitive deficits do not interfere with capacity for independence in everyday

activities (i.e., complex instrumental activities of daily living such as paying bills or

managing medications are preserved, but greater effort, compensatory strategies, or

accommodation may be required).

C. The cognitive deficits do not occur exclusively in the context of a delirium.

D. The cognitive deficits are not better explained by another mental disorder (e.g., major

depressive disorder, schizophrenia).

Specify whether due to:

Alzheimer’s disease (pp. 611-614)

Frontotemporal lobar degeneration (pp. 614-618)

Lewy body disease (pp. 618-621)

Vascular disease (pp. 621-624)

Traumatic brain injury (pp. 624-627)

Substance/medication use (pp. 627-632)

HIV infection (pp. 632-634)

Prion disease (pp. 634-636)

Parkinson’s disease (pp. 636-638)

Huntington’s disease (pp. 638-641)

Another medical condition (pp. 641-642)

Multiple etiologies (pp. 642-643)

Unspecified (p. 643)

Coding note: For mild neurocognitive disorder due to any of the medical etiologies listed

above, code 331.83 (G31.84). Do not use additional codes for the presumed etiological

medical conditions. For substance/medication-induced mild neurocognitive disorder, code

based on type of substance; see “Substance/Medication-Induced Major or Mild Neurocognitive Disorder.” For unspecified mild neurocognitive disorder, code 799.59 (R41.9).

Specify:

Without behavioral disturbance: If the cognitive disturbance is not accompanied by

any clinically significant behavioral disturbance.

With behavioral disturbance (specify disturbance): If the cognitive disturbance is accompanied by a clinically significant behavioral disturbance (e.g., psychotic symptoms,

mood disturbance, agitation, apathy, or other behavioral symptoms).

Subtypes

Major and mild neurocognitive disorders (NCDs) are primarily subtyped according to the

known or presumed etiological/pathological entity or entities underlying the cognitive decline. These subtypes are distinguished on the basis of a combination of time course, characteristic domains affected, and associated symptoms. For certain etiological subtypes, the

diagnosis depends substantially on the presence of a potentially causative entity, such as Parkinson's or Huntington's disease, or a traumatic brain injury or stroke in the appropriate time

period. For other etiological subtypes (generally the neurodegenerative diseases like Alzheimer's disease, frontotemporal lobar degeneration, and Lewy body disease), the diagnosis is

based primarily on the cognitive, behavioral, and functional symptoms. Typically, the differentiation among these syndromes that lack an independentiy recognized etiological entity is

clearer at the level of major NCD than at the level of mild NCD, but sometimes characteristic

symptoms and associated features are present at the mild level as well.

NCDs are frequently managed by clinicians in multiple disciplines. For many subtypes, multidisciplinary international expert groups have developed specialized consensus criteria based on clinicopathological correlation with underlying brain pathology. The

subtype criteria here have been harmonized with those expert criteria.

Specifiers

Evidence for distinct behavioral features in NCDs has been recognized, particularly in the

areas of psychotic symptoms and depression. Psychotic features are common in many

NCDs, particularly at the mild-to-moderate stage of major NCDs due to Alzheimer's disease, Lewy body disease, and frontotemporal lobar degeneration. Paranoia and other

delusions are common features, and often a persecutory theme may be a prominent aspect

of delusional ideation. In contrast to psychotic disorders with onset in earlier life (e.g.,

schizophrenia), disorganized speech and disorganized behavior are not characteristic of

psychosis in NCDs. Hallucinations may occur in any modality, although visual hallucinations are more common in NCDs than in depressive, bipolar, or psychotic disorders.

Mood disturbances, including depression, anxiety, and elation, may occur. Depression

is common early in the course (including at the mild NCD level) of NCD due to Alzheimer's disease and Parkinson's disease, while elation may occur more commonly in frontotemporal lobar degeneration. When a full affective syndrome meeting diagnostic criteria

for a depressive or bipolar disorder is present, that diagnosis should be coded as well.

Mood symptoms are increasingly recognized to be a significant feature in the earliest stages

of mild NCDs such that clinical recognition and intervention may be important.

Agitation is common in a wide variety of NCDs, particularly in major NCD of moderate to severe severity, and often occurs in the setting of confusion or frustration. It may

arise as combative behaviors, particularly in the context of resisting caregiving duties such

as bathing and dressing. Agitation is characterized as disruptive motor or vocal activity

and tends to occur with advanced stages of cognitive impairment across all of the NCDs.

Individuals with NCD can present with a wide variety of behavioral symptoms that

are the focus of treatment. Sleep disturbance is a common symptom that can create a need

for clinical attention and may include symptoms of insomnia, hypersomnia, and circadian

rhythm disturbances.

Apathy is common in mild and mild major NCD. It is observed particularly in NCD due

to Alzheimer's disease and may be a prominent feature of NCD due to frontotemporal

lobar degeneration. Apathy is typically characterized by diminished motivation and reduced goal-directed behavior accompanied by decreased emotional responsiveness.

Symptoms of apathy may manifest early in the course of NCDs when a loss of motivation

to pursue daily activities or hobbies may be observed.

Other important behavioral symptoms include wandering, disinhibition, hyperphagia, and hoarding. Some of these symptoms are characteristic of specific disorders, as discussed in the relevant sections. When more than one behavioral disturbance is observed,

each type should be noted in writing with the specifier "with behavioral symptoms."

Diagnostic Features

Major and mild NCDs exist on a spectrum of cognitive and functional impairment. Major

NCD corresponds to the condition referred to in DSM-IV as dementia, retained as an alternative in this volume. The core feature of NCDs is acquired cognitive decline in one or

more cognitive domains (Criterion A) based on both 1) a concern about cognition on the

part of the individual, a knowledgeable informant, or the clinician, and 2) performance on

an objective assessment that falls below the expected level or that has been observed to decline over time. Both a concern and objective evidence are required because they are complementary. When there is an exclusive focus on objective testing, a disorder may go

undiagnosed in high-functioning individuals whose currently "normal" performance actually represents a substantial decline in abilities, or an illness may be incorrectly diagnosed in individuals whose currently "low" performance does not represent a change

from their own baseline or is a result of extraneous factors like test conditions or a passing

illness. Alternatively, excessive focus on subjective symptoms may fail to diagnose illness

in individuals with poor insight, or whose informants deny or fail to notice their symptoms,

or it may be overly sensitive in the so-called worried well.

A cognitive concern differs from a complaint in that it may or may not be voiced spontaneously. Rather, it may need to be elicited by careful questioning about specific symptoms that commonly occur in individuals with cognitive deficits (see Table 1 in the

introduction to this chapter). For example, memory concerns include difficulty remembering a short grocery list or keeping track of the plot of a television program; executive concerns include difßculty resuming a task when interrupted, organizing tax records, or

planning a holiday meal. At the mild NCD level, the individual is likely to describe these

tasks as being more difficult or as requiring extra time or effort or compensatory strategies.

At the major NCD level, such tasks may only be completed with assistance or may be

abandoned altogether. At the mild NCD level, individuals and their families may not notice such symptoms or may view them as normal, particularly in the elderly; thus, careful

history taking is of paramount importance. The difficulties must represent changes rather

than lifelong patterns: the individual or informant may clarify this issue, or the clinician

can infer change from prior experience with the patient or from occupational or other

clues. It is also critical to determine that the difficulties are related to cognitive loss rather

than to motor or sensory limitations.

Neuropsychological testing, with performance compared with norms appropriate to

the patient's age, educational attainment, and cultural background, is part of the standard

evaluation of NCDs and is particularly critical in the evaluation of mild NCD. For major

NCD, performance is typically 2 or more standard deviations below appropriate norms

(3rd percentile or below). For mild NCD, performance typically lies in the 1-2 standard deviation range (between the 3rd and 16th percentiles). However, neuropsychological testing is not available in all settings, and neuropsychological thresholds are sensitive to the

specific test(s) and norms employed, as well as to test conditions, sensory limitations, and

intercurrent illness. A variety of brief office-based or "bedside" assessments, as described

in Table 1, can also supply objective data in settings where such testing is unavailable or

infeasible. In any case, as with cognitive concerns, objective performance must be interpreted in light of the individual's prior performance. Optimally, this information would

be available from a prior administration of the same test, but often it must be inferred

based on appropriate norms, along with the individual's educational history, occupation,

and other factors. Norms are more challenging to interpret in individuals with very high

or very low levels of education and in individuals being tested outside their own language

or cultural background.

Criterion B relates to the individual's level of independence in everyday functioning.

Individuals with major NCD will have impairment of sufficient severity so as to interfere

with independence, such that others will have to take over tasks that the individuals were

previously able to complete on their own. Individuals with mild NCD will have preserved

independence, although there may be subtle interference with function or a report that

tasks require more effort or take more time than previously.

The distinction between major and mild NCD is inherently arbitrary, and the disorders

exist along a continuum. Precise thresholds are therefore difficult to determine. Careful

history taking, observation, and integration with other findings are required, and the implications of diagnosis should be considered when an individual's clinical manifestations

lie at a boundary.

Associated Features Supporting Diagnosis

Typically the associated features that support a diagnosis of major or mild NCD will be

specific to the etiological subtype (e.g., neuroleptic sensitivity and visual hallucinations in

NCD due to Lewy body disease). Diagnostic features specific to each of the subtypes are

found in the relevant sections.

Prevalence

The prevalence of NCD varies widely by age and by etiological subtype. Overall prevalence estimates are generally only available for older populations. Among individuals

older than 60 years, prevalence increases steeply with age, so prevalence estimates are

more accurate for narrow age bands than for broad categories such as "over 65" (where the

mean age can vary greatly with the life expectancy of the given population). For those etiological subtypes occurring across the lifespan, prevalence estimates for NCD are likely to

be available, if at all, only as the fraction of individuals who develop NCD among those

with the relevant condition (e.g., traumatic brain injury, HIV infection).

Overall prevalence estimates for dementia (which is largely congruent with major

NCD) are approximately l%-2% at age 65 years and as high as 30% by age 85 years. The

prevalence of mild NCD is very sensitive to the definition of the disorder, particularly in

community settings, where evaluations are less detailed. In addition, in contrast with clinical settings, where cognitive concern must be high to seek and locate care, there may be a

less clear decline from baseline functioning. Estimates of the prevalence of mild cognitive

impairment (which is substantially congruent with mild NCD) among older individuals

are fairly variable, ranging from 2% to 10% at age 65 and 5% to 25% by age 85.

Development and Course

The course of NCD varies across etiological subtypes, and this variation can be useful in

differential diagnosis. Some subtypes (e.g., those related to traumatic brain injury or

stroke) typically begin at a specific time and (at least after initial symptoms related to inflammation or swelling subside) remain static. Others may fluctuate over time (although

if this occurs, the possibility of delirium superimposed on NCD should be considered).

NCDs due to neurodegenerative diseases like Alzheimer's disease or frontotemporal

lobar degeneration typically are marked by insidious onset and gradual progression, and

the pattem of onset of cognitive deficits and associated features helps to distinguish among

them.

NCDs with onset in childhood and adolescence may have broad repercussions for social and intellectual development, and in this setting intellectual disability (intellectual

developmental disorder) and/or other neurodevelopmental disorders may also be diagnosed to capture the full diagnostic picture and ensure the provision of a broad range of

services. In older individuals, NCDs often occur in the setting of medical illnesses, frailty,

and sensory loss, which complicate the clinical picture for diagnosis and treatment.

When cognitive loss occurs in youth to midlife, individuals and families are likely to

seek care. NCDs are typically easiest to identify at younger ages, although in some settings

malingering or other factitious disorders may be a concern. Very late in life, cognitive

symptoms may not cause concern or may go unnoticed. In late life, mild NCD must also be

distinguished from the more modest deficits associated with "normal aging," although a

substantial fraction of what has been ascribed to normal aging likely represents prodromal

phases of various NCDs. In addition, it becomes harder to recognize mild NCD with age

because of the increasing prevalence of medical illness and sensory deficits. It becomes

harder to differentiate among subtypes with age because there are multiple potential sources

of neurocognitive decline.

Risk and Prognostic Factors

Risk factors vary not only by etiological subtype but also by age at onset within etiological

subtypes. Some subtypes are distributed throughout the lifespan, whereas others occur

exclusively or primarily in late life. Even within the NCDs of aging, the relative prevalence

varies with age: Alzheimer's disease is uncommon before age 60 years, and the prevalence

increases steeply thereafter, while the overall less common frontotemporal lobar degeneration has earlier onset and represents a progressively smaller fraction of NCDs with age.

Genetic and physiological. The strongest risk factor for major and mild NCDs is age,

primarily because age increases the risk of neurodegenerative and cerebrovascular disease. Female gender is associated with higher prevalence of dementia overall, and especially

Alzheimer's disease, but this difference is largely, if not wholly, attributable to greater longevity in females.

Culture-Related Diagnostic issues

Individuals' and families' level of awareness and concern about neurocognitive symptoms may vary across ethnic and occupational groups. Neurocognitive symptoms are

more likely to be noticed, particularly at the mild level, in individuals who engage in complex occupational, domestic, or recreational activities. In addition, norms for neuropsychological testing tend to be available only for broad populations, and thus they may not

be easily applicable to individuals with less than high school education or those being

evaluated outside their primary language or culture.

Gender-Related Diagnostic issues

Like age, culture, and occupation, gender issues may affect the level of concern and awareness of cognitive symptoms. In addition, for late-life NCDs, females are likely to be older,

to have more medical comorbidity, and to live alone, which can complicate evaluation and

treatment. In addition, there are gender differences in the frequency of some of the etiological subtypes.

Diagnostic iVlarkers

In addition to a careful history, neuropsychological assessments are the key measures for

diagnosis of NCDs, particularly at the mild level, where functional changes are minimal

and symptoms more subtle. Ideally, individuals will be referred for formal neuropsychological testing, which will provide a quantitative assessment of all relevant domains and

thus help with diagnosis; provide guidance to the family on areas where the individual

may require more support; and serve as a benchmark for further decline or response to

therapies. When such testing is unavailable or not feasible, the brief assessments in Table 1

can provide insight into each domain. More global brief mental status tests may be helpful

but may be insensitive, particularly to modest changes in a single domain or in those with

high premorbid abilities, and may be overly sensitive in those with low premorbid abilities.

In distinguishing among etiological subtypes, additional diagnostic markers may

come into play, particularly neuroimaging studies such as magnetic resonance imaging

scans and positron emission tomography scans. In addition, specific markers may be involved in the assessment of specific subtypes and may become more important as additional research findings accumulate over time, as discussed in the relevant sections.

Functional Consequences of

Major and Mild Neurocognitive Disorders

By definition, major and mild NCDs affect functioning, given the central role of cognition in

human life. Thus, the criteria for the disorders, and the threshold for differentiating mild

from major NCD, are based in part on functional assessment. Within major NCD there is a

broad range of functional impairment, as implemented in the severity specifiers. In addition,

the specific functions that are compromised can help identify the cognitive domains affected,

particularly when neuropsychological testing is not available or is difficult to interpret.

Differential Diagnosis

Normal cognition. The differential diagnosis between normal cognition and mild NCD,

as between mild and major NCD, is challenging because the boundaries are inherently arbitrary. Careful history taking and objective assessment are critical to these distinctions. A

longitudinal evaluation using quantified assessments may be key in detecting mild NCD.

Delirium. Both mild and major NCD may be difficult to distinguish from a persistent delirium, which can co-occur. Careful assessment of attention and arousal will help to make

the distinction.

Major depressive disorder. The distinction between mild NCD and major depressive

disorder, which may co-occur with NCD, can also be challenging. Specific patterns of cognitive deficits may be helpful. For example, consistent memory and executive function

deficits are typical of Alzheimer's disease, whereas nonspecific or more variable performance is seen in major depression. Alternatively, treatment of the depressive disorder

with repeated observation over time may be required to make the diagnosis.

Specific learning disorder and other neurodevelopmental disorders. A careful clarification of the individual's baseline status will help distinguish an NCD from a specific

learning disorder or other neurodevelopmental disorders. Additional issues may enter the

differential for specific etiological subtypes, as described in the relevant sections.

Comorbidity

NCDs are common in older individuals and thus often co-occur with a wide variety of agerelated diseases that may complicate diagnosis or treatment. Most notable of these is

delirium, for which NCD increases the risk. In older individuals, a delirium during hospitalization is, in many cases, the first time that an NCD is noticed, although a careful history will often reveal evidence of earlier decline. Mixed NCDs are also common in older

individuals, as many etiological entities increase in prevalence with age. In younger individuals, NCD often co-occurs with neurodevelopmental disorders; for example, a head in­

jury in a preschool child may also lead to significant developmental and learning issues.

Additional comorbidity of NCD is often related to the etiological subtype, as discussed in

the relevant sections.

Major or Mild Neurocognitive Disorder

Due to Alzheimer’s Disease

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. There is insidious onset and gradual progression of impairment in one or more cognitive

domains (for major neurocognitive disorder, at least two domains must be impaired).

C. Criteria are met for either probable or possible Alzheimer’s disease as follows:

For major neurocognitive disorder:

Probable Alzheimer’s disease is diagnosed if either of the following is present; otherwise, possible Alzheimer’s disease should be diagnosed.

1. Evidence of a causative Alzheimer’s disease genetic mutation from family history

or genetic testing.

2. All three of the following are present:

a. Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing).

b. Steadily progressive, gradual decline in cognition, without extended plateaus.

c. No evidence of mixed etiology (i.e., absence of other neurodegenerative or

cerebrovascular disease, or another neurological, mental, or systemic disease

or condition likely contributing to cognitive decline).

For mild neurocognitive disorder:

Probable Alzheimer’s disease is diagnosed if there is evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history.

Possible Alzheimer’s disease is diagnosed if there is no evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history, and all

three of the following are present:

1. Clear evidence of decline in memory and learning.

2. Steadily progressive, gradual decline in cognition, without extended plateaus.

3. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely

contributing to cognitive decline).

D. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Coding note: For probable major neurocognitive disorder due to Alzheimer’s disease,

with behavioral disturbance, code first 331.0 (G30.9) Alzheimer’s disease, followed by

294.11 (F02.81) major neurocognitive disorder due to Alzheimer’s disease. For probable

neurocognitive disorder due to Alzheimer’s disease, without behavioral disturbance, code

first 331.0 (G30.9) Alzheimer’s disease, followed by 294.10 (F02.80) major neurocognitive

disorder due to Alzheimer’s disease, without behavioral disturbance.

For possible major neurocognitive disorder due to Alzheimer’s disease, code 331.9

(G31.9) possible major neurocognitive disorder due to Alzheimer’s disease. (Note: Do not

use the additional code for Alzheimer’s disease. Behavioral disturbance cannot be coded

but should still be indicated in writing.)

For mild neurocognitive disorder due to Alzheimer’s disease, code 331.83 (G31.84).

(Note: Do not use the additional code for Alzheimer’s disease. Behavioral disturbance

cannot be coded but should still be indicated in writing.)

Diagnostic Features

Beyond the neurocognitive disorder (NCD) syndrome (Criterion A), the core features of major or mild NCD due to Alzheimer's disease include an insidious onset and gradual progression of cognitive and behavioral symptoms (Criterion B). The typical presentation is

amnestic (i.e., with impairment in memory and learning). Unusual nonamnestic presentations, particularly visuospatial and logopenic aphasie variants, also exist. At the mild

NCD phase, Alzheimer's disease manifests typically with impairment in memory and learning, sometimes accompanied by deficits in executive function. At the major NCD phase,

visuoconstructional/perceptual motor ability and language will also be impaired, particularly when the NCD is moderate to severe. Social cognition tends to be preserved until

late in the course of the disease.

A level of diagnostic certainty must be specified denoting Alzheimer's disease as the

"probable" or "possible" etiology (Criterion C). Probable Alzheimer's disease is diagnosed in

both major and mild NCD if there is evidence of a causative Alzheimer's disease gene, either from genetic testing or from an autosomal dominant family history coupled with autopsy confirmation or a genetic test in an affected family member. For major NCD, a

typical clinical picture, without extended plateaus or evidence of mixed etiology, can also

be diagnosed as due to probable Alzheimer's disease. For mild NCD, given the lesser degree of certainty that the deficits will progress, these features are only sufficient for a

possible Alzheimer's etiology. If the etiology appears mixed, mild NCD due to multiple etiologies should be diagnosed. In any case, for both mild and major NCD due to Alzheimer's disease, the clinical features must not suggest another primary etiology for the NCD

(Criterion D).

Associated Features Supporting Diagnosis

In specialty clinical settings, approximately 80% of individuals with major NCD due to

Alzheimer's disease have behavioral and psychological manifestations; these features are

also frequent at the mild NCD stage of impairment. These symptoms are as or more distressing than cognitive manifestations and are frequently the reason that health care is

sought. At the mild NCD stage or the mildest level of major NCD, depression and/or apathy are often seen. With moderately severe major NCD, psychotic features, irritability,

agitation, combativeness, and wandering are common. Late in the illness, gait disturbance, dysphagia, incontinence, myoclonus, and seizures are observed.

Prevaience

The prevalence of overall dementia (major NCD) rises steeply with age. In high-income

countries, it ranges from 5% to 10% in the seventh decade to at least 25% thereafter. U.S.

census data estimates suggest that approximately 7% of individuals diagnosed with Alzheimer's disease are between ages 65 and 74 years, 53% are between ages 75 and 84 years,

and 40% are 85 years and older. The percentage of dementias attributable to Alzheimer's

disease ranges from about 60% to over 90%, depending on the setting and diagnostic criteria. Mild NCD due to Alzheimer's disease is likely to represent a substantial fraction of

mild cognitive impairment (MCI) as well.

Development and Course

Major or mild NCD due to Alzheimer's disease progresses gradually, sometimes with

brief plateaus, through severe dementia to death. The mean duration of survival after di­

agnosis is approximately 10 years, reflecting the advanced age of the majority of individuals rather than the course of the disease; some individuals can live with the disease for as

long as 20 years. Y.ate-stage individuals are eventually mute and bedbound. Death most

commonly results from aspiration in those who survive through the full course. In mild

NCD due to Alzheimer's disease, impairments increase over time, and functional status

gradually declines until symptoms reach the threshold for the diagnosis of major NCD.

The onset of symptoms is usually in the eighth and ninth decades; early-onset forms

seen in the fifth and sixth decades are often related to known causative mutations. Symptoms and pathology do not differ markedly at different onset ages. However, younger individuals are more likely to survive the full course of the disease, while older individuals

are more likely to have numerous medical comorbidities that affect the course and management of the illness. Diagnostic complexity is higher in older adults because of the increased likelihood of comorbid medical illness and mixed pathology.

Risk and Prognostic Factors

Environmental. Traumatic brain injury increases risk for major or mild NCD due to Alzheimer's disease.

Genetic and physiological. Age is the strongest risk factor for Alzheimer's disease. The

genetic susceptibility polymorphism apolipoprotein E4 increases risk and decreases age

at onset, particularly in homozygous individuals. There are also extremely rare causative

Alzheimer's disease genes. Individuals with Down's syndrome (trisomy 21) develop Alzheimer's disease if they survive to midlife. Multiple vascular risk factors influence risk for

Alzheimer's disease and may act by increasing cerebrovascular pathology or also through

direct effects on Alzheimer pathology.

Culture-Related Diagnostic Issues

Detection of an NCD may be more difficult in cultural and socioeconomic settings where

memory loss is considered normal in old age, where older adults face fewer cognitive demands in everyday life, or where very low educational levels pose greater challenges to

objective cognitive assessment.

Diagnostic IVIarkers

Cortical atrophy, amyloid-predominant neuritic plaques, and tau-predominant neurofibrillary tangles are hallinarks of the pathological diagnosis of Alzheimer's disease and may be

confirmed via postmortem histopathological examination. For early-onset cases with autosomal dominant inheritance, a mutation in one of the known causative Alzheimer's disease

genes—amyloid precursor protein (APP), presenilin 1 (PSENl), or presenilin 2 (PSEN2)—

may be involved, and genetic testing for such mutations is commercially available, at least

for PSENl. Apolipoprotein E4 cannot serve as a diagnostic marker because it is only a risk

factor and neither necessary nor sufficient for disease occurrence.

Since amyloid beta-42 deposition in the brain occurs early in the pathophysiological

cascade, amyloid-based diagnostic tests such as amyloid imaging on brain positron emission tomography (PET) scans and reduced levels of amyloid beta-42 in the cerebrospinal

fluid (CSF) may have diagnostic value. Signs of neuronal injury, such as hippocampal and

temporoparietal cortical atrophy on a magnetic resonance image scan, temporoparietal

hypometabolism on a fluorodeoxyglucose PET scan, and evidence for elevated total tau

and phospho-tau levels in CSF, provide evidence of neuronal damage but are less specific

for Alzheimer's disease. At present, these biomarkers are not fully validated, and many

are available only in tertiary care settings. However, some of them, along with novel biomarkers, will likely move into wider clinical practice in the coming years.

Functional Consequences of Major or Mild

Neurocognitive Disorder Due to Alzheimer’s Disease

The prominence of memory loss can cause significant difficulties relatively early in the

course. Social cognition (and thus social functioning) and procedural memory (e.g., dancing, playing musical instruments) may be relatively preserved for extended periods.

Differential Diagnosis

Other neurocognitive disorders. Major and mild NCDs due to other neurodegenerative processes (e.g., Lewy body disease, frontotemporal lobar degeneration) share the insidious onset and gradual decline caused by Alzheimer's disease but have distinctive core

features of their own. In major or mild vascular NCD, there is typically history of stroke

temporally related to the onset of cognitive impairment, and infarcts or white matter hyperintensities are judged sufficient to account for the clinical picture. However, particularly when there is no clear history of stepwise decline, major or mild vascular NCD can

share many clinical features with Alzheimer's disease.

Other concurrent, active neurological or systemic illness. Other neurological or systemic illness should be considered if there is an appropriate temporal relationship and

severity to account for the clinical picture. At the mild NCD level, it may be difficult to distinguish an Alzheimer's disease etiology from that of another medical condition (e.g., thyroid disorders, vitamin Bj2 deficiency).

Major depressive disorder. Particularly at the mild NCD level, the differential diagnosis

also includes major depression. The presence of depression may be associated with reduced daily functioning and poor concentration that may resemble an NCD, but improvement with treatment of depression may be useful in making the distinction.

Comorbidity

Most individuals with Alzheimer's disease are elderly and have multiple medical conditions

that can complicate diagnosis and influence the clinical course. Major or mild NCD due to

Alzheimer's disease commonly co-occurs with cerebrovascular disease, which contributes

to the clinical picture. When a comorbid condition contributes to the NCD in an individual

with Alzheimer's disease, then NCD due to multiple etiologies should be diagnosed.

Major or Mild Frontotemporal

Neurocognitive Disorder

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. The disturbance has insidious onset and gradual progression.

C. Either (1) or (2);

1. Behavioral variant;

a. Three or more of the following behavioral symptoms:

i. Behavioral disinhibition.

ii. Apathy or inertia.

iii. Loss of sympathy or empathy.

iv. Perseverative, stereotyped or compulsive/ritualistic behavior.

v. Hyperorality and dietary changes.

b. Prominent decline in social cognition and/or executive abilities.

2. Language variant:

a. Promi(Qent decline in language ability, in the form of speech production, word

finding, object naming, grammar, or word comprehension.

D. Relative sparing of learning and memory and perceptual-motor function.

E. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Probable frontotemporal neurocognitive disorder is diagnosed if either of the following

is present; othenwise, possible frontotemporal neurocognitive disorder should be diagnosed:

1. Evidence of a causative frontotemporal neurocognitive disorder genetic mutation, from

either family history or genetic testing.

2. Evidence of disproportionate frontal and/or temporal lobe involvement from neuroimaging.

Possible frontotemporal neurocognitive disorder is diagnosed if there is no evidence

of a genetic mutation, and neuroimaging has not been performed.

Coding note: For probable major neurocognitive disorder due to frontotemporal lobar degeneration, with behavioral disturbance, code first 331.19 (G31.09) frontotemporal disease, followed by 294.11 (F02.81) probable major neurocognitive disorder due to

frontotemporal lobar degeneration, with behavioral disturbance. For probable major neurocognitive disorder due to frontotemporal lobar degeneration, without behavioral disturbance, code first 331.19 (G31.09) frontotemporal disease, followed by 294.10 (F02.80)

probable major neurocognitive disorder due to frontotemporal lobar degeneration, without

behavioral disturbance.

For possible major neurocognitive disorder due to frontotemporal lobar degeneration, code

331.9 (G31.9) possible major neurocognitive disorder due to frontotemporal lobar degeneration. (Note: Do not use the additional code for frontotemporal disease. Behavioral disturbance cannot be coded but should still be indicated in writing.)

For mild neurocognitive disorder due to frontotemporal lobar degeneration, code 331.83

(031.84). (Note: Do not use the additional code for frontotemporal disease. Behavioral

disturbance cannot be coded but should still be indicated in writing.)

Diagnostic Features

Major or mild frontotemporal neurocognitive disorder (NCD) comprises a number of syndromic variants characterized by the progressive development of behavioral and personality

change and/or language impairment. The behavioral variant and three language variants (semantic, agrammatic/nonfluent, and logopenic) exhibit distinct patterns of brain atrophy and

some distinctive neuropathology. The criteria must be met for either the behavioral or the language variant to make the diagnosis, but many individuals present with features of both.

Individuals with behavioral-variant major or mild frontotemporal NCD present with

varying degrees of apathy or disinhibition. They may lose interest in socialization, selfcare, and personal responsibilities, or display socially inappropriate behaviors. Insight is

usually impaired, and this often delays medical consultation. The first referral is often to a

psychiatrist. Individuals may develop changes in social style, and in religious and political

beliefs, with repetitive movements, hoarding, changes in eating behavior, and hyperorality. In later stages, loss of sphincter control may occur. Cognitive decline is less prominent,

and formal testing may show relatively few deficits in the early stages. Common neurocognitive symptoms are lack of planning and organization, distractibility, and poor judgment. Deficits in executive function, such as poor performance on tests of mental

flexibility, abstract reasoning, and response inhibition, are present, but learning and memory are relatively spared, and perceptual motor abilities are almost always preserved in

the early stages.

Individuals with language-variant major or mild frontotemporal NCD present with primary progressive aphasia with gradual onset, with three subtypes commonly described:

semantic variant, agrammatic/nonfluent variant, and logopenic variant, and each variant

has distinctive features and corresponding neuropathology.

"Probable" is distinguished from "possible" frontotemporal NCD by the presence of

causative genetic factors (e.g., mutations in the gene coding for microtubule-associated protein tau) or by the presence of distinctive atrophy or reduced activity in frontotemporal regions on structural or functional imaging.

Associated Features Supporting Diagnosis

Extrapyramidal features may be prominent in some cases, with an overlap with syndromes such as progressive supranuclear palsy and corticobasal degeneration. Features of

motor neuron disease may be present in some cases (e.g., muscle atrophy, weakness). A

subset of individuals develop visual hallucinations.

Prevalence

Major or mild frontotemporal NCD is a common cause of early-onset NCD in individuals

younger than 65 years. Population prevalence estimates are in the range of 2-10 per

100,000. Approximately 20%-25% of cases of frontotemporal NCD occur in individuals

older than 65 years. Frontotemporal NCD accounts for about 5% of all cases of dementia in

unselected autopsy series. Prevalence estimates of behavioral variant and semantic language variant are higher among males, and prevalence estimates of nonfluent language

variant are higher among females.

Development and Course

Individuals with major or mild frontotemporal NCD commonly present in the sixth decade of life, although the age at onset varies from the third to the ninth decades. The disease is gradually progressive, with median survival being 6-11 years after symptom onset

and 3-4 years after diagnosis. Survival is shorter and decline is faster in major or mild frontotemporal NCD than in typical Alzheimer's disease.

Risk and Prognostic Factors

Genetic and physiological. Approximately 40% of individuals with major or mild frontotemporal NCD have a family history of early-onset NCD, and approximately 10% show an

autosomal dominant inheritance pattern. A number of genetic factors have been identified,

such as mutations in the gene encoding the microtubule associated protein tau (MAPT), the

granulin gene (CRN), and the C90RF72 gene. A number of families with causative mutations have been identified (see the section "Diagnostic Markers" for this disorder), but many

individuals with known familial transmission do not have a known mutation. The presence

of motor neuron disease is associated with a more rapid deterioration.

Diagnostic IVIarkers

Computed tomography (CT) or structural magnetic resonance imaging (MRI) may show

distinct patterns of atrophy. In behavioral-variant major or mild frontotemporal NCD,

both frontal lobes (especially the medial frontal lobes) and the anterior temporal lobes are

atrophic. In semantic language-variant major or mild frontotemporal NCD, the middle,

inferior, and anterior temporal lobes are atrophic bilaterally but asymmetrically, with the

left side usually being more affected. Nonfluent language-variant major or mild frontotemporal NCD is associated with predominantly left posterior frontal-insular atrophy.

The logopenic variant of major or mild frontotemporal NCD is associated with predominantly left posterior perisylvian or parietal atrophy. Functional imaging demonstrates hypoperfusion and/or cortical hypometabolism in the corresponding brain regions, which

may be present in the early stages in the absence of structural abnormality. Emerging biomarkers for Alzheimer's disease (e.g., cerebrospinal fluid amyloid-beta and tau levels, and

amyloid imaging) may help in the differential diagnosis, but the distinction from Alzheimer's disease can remain difficult (the logopenic variant is in fact often a manifestation of

Alzheimer's disease).

In familial cases of frontotemporal NCD, the identification of genetic mutations may

help confirm the diagnosis. Mutations associated with frontotemporal NCD include

the genes encoding microtubule-associated protein tau (MAPT) and granulin (GRN),

C90RF72, transactive response DNA-binding protein of 43 kDa (TDP-43, or TARDBP),

valosin-containing protein (VCP), chromatin modifying protein 2B (CHMP2B), and fused

in sarcoma protein (PUS).

Functional Consequences of Major or Mild

Frontotemporal Neurocognitive Disorder

Because of the relative early age at onset of the disorder, the disorder oftens affects workplace and family life. Because of the involvement of language and/or behavior, function is

often more severely impaired relatively early in the course. For individuals with the behavioral variant, prior to diagnostic clarification there may be significant family disruption, legal involvement, and problems in the workplace because of socially inappropriate

behaviors. The functional impairment due to behavioral change and language dysfunction, which can include hyperorality, impulsive wandering, and other dishinhibited behaviors, may far exceed that due to the cognitive disturbance and may lead to nursing

home placement or institutionalization. These behaviors can be severely disruptive, even

in structured care settings, particularly when the individuals are otherwise healthy, nonfrail, and free of other medical comorbidities.

Differential Diagnosis

Other neurocognitive disorders. Other neurodegenerative diseases may be distinguished

from major or mild frontotemporal NCD by their characteristic features. In major or mild

NCD due to Alzheimer's disease, decline in learning and memory is an early feature.

However, 10%-30% of patients presenting with a syndrome suggestive of major or mild

frontotemporal NCD are found at autopsy to have Alzheimer's disease pathology. This occurs more frequently in individuals who present with progressive dysexecutive syndromes in the absence of behavioral changes or movement disorder or in those with the

logopenic variant.

In major or mild NCD with Lewy bodies, core and suggestive features of Lewy bodies

must be present. In major or mild NCD due to Parkinson's disease, spontaneous parkinsonism emerges well before the cognitive decline. In major or mild vascular NCD, depending on affected brain regions, there may also be loss of executive ability and behavioral

changes such as apathy, and this disorder should be considered in the differential diagnosis. However, history of a cerebrovascular event is temporally related to the onset of cognitive impairment in major or mild vascular NCD, and neuroimaging reveals infarctions

or white matter lesions sufficient to account for the clinical picture.

Other neurological conditions. Major or mild frontotemporal NCD overlaps with progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease

clinically as well as pathologically. Progressive supranuclear palsy is characterized by

supranuclear gaze palsies and axial-predominant parkinsonism. Pseudobulbar signs may

be present, and rétropulsion is often prominent. Neurocognitive assessment shows psychomotor slowing, poor working memory, and executive dysfunction. Corticobasal degeneration presents with asymmetric rigidity, limb apraxia, postural instability, myoclonus,

alien limb phenomenon, and cortical sensory loss. Many individuals with behavioral-variant

major or mild frontotemporal NCD show features of motor neuron disease, which tend to

be mixed upper and predominantly lower motor neuron disease.

Other mental disorders and medical conditions. Behavioral-variant major or mild frontotemporal NCD may be mistaken for a primary mental disorder, such as major depression,

bipolar disorders, or schizophrenia, and individuals with this variant often present initially

to psychiatry. Over time, the development of progressive neurocognitive difficulties will

help to make the distinction. A careful medical evaluation will help to exclude treatable

causes of NCDs, such as metabolic disturbances, nutritional deficiencies, and infections.

Major or Mild Neurocognitive Disorder

With Lewy Bodies

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. The disorder has an insidious onset and gradual progression.

C. The disorder meets a combination of core diagnostic features and suggestive diagnostic features for either probable or possible neurocognitive disorder with Lewy bodies.

For probable major or mild neurocognitive disorder with Lewy bodies, the individual has two core features, or one suggestive feature with one or more core features.

For possible major or mild neurocognitive disorder with Lewy bodies, the individual has only one core feature, or one or more suggestive features.

1. Core diagnostic features:

a. Fluctuating cognition with pronounced variations in attention and alertness.

b. Recurrent visual hallucinations that are well formed and detailed.

c. Spontaneous features of parkinsonism, with onset subsequent to the development of cognitive decline.

2. Suggestive diagnostic features;

a. Meets criteria for rapid eye movement sleep behavior disorder.

b. Severe neuroleptic sensitivity.

D. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Coding note: For probable major neurocognitive disorder with Lewy bodies, with behavioral disturbance, code first 331.82 (G31.83) Lewy body disease, followed by 294.11

(F02.81 ) probable major neurocognitive disorder with Lewy bodies, with behavioral disturbance. For probable major neurocognitive disorder with Lewy bodies, without behavioral

disturbance, code first 331.82 (G31.83) Lewy body disease, followed by 294.10 (F02.80)

probable major neurocognitive disorder with Lewy bodies, without behavioral disturbance.

For possible major neurocognitive disorder with Lewy bodies, code 331.9 (G31.9) possible

major neurocognitive disorder with Lewy bodies. (Note: Do not use the additional code for

Lewy body disease. Behavioral disturbance cannot be coded but should still be indicated

in writing.)

For mild neurocognitive disorder with Lewy bodies, code 331.83 (G31.84). (Note: Do not

use the additional code for Lewy body disease. Behavioral disturbance cannot be coded

but should still be indicated in writing.)

Diagnostic Features

Major or mild neurocognitive disorder with Lewy bodies (NCDLB), in the case of major

neurocognitive disorder (NCD), corresponds to the condition known as dementia with

Lewy bodies (DLB). The disorder includes not only progressive cognitive impairment

(with early changes in complex attention and executive function rather than learning and

memory) but also recurrent complex visual hallucinations; and concurrent symptoms of

rapid eye movement (REM) sleep behavior disorder (which can be a very early manifestation); as well as hallucinations in other sensory modalities, depression, and delusions.

The symptoms fluctuate in a pattern that can resemble a delirium, but no adequate underlying cause can be found. The variable presentation of NCDLB symptoms reduces the likelihood of all symptoms being observed in a brief clinic visit and necessitates a thorough

assessment of caregiver observations. The use of assessment scales specifically designed to

assess fluctuation may aid in diagnosis. Another core feature is spontaneous parkinsonism, which must begin after the onset of cognitive decline; by convention, major cognitive

deficits are observed at least 1 year before the motor symptoms. The parkinsonism must

also be distinguished from neuroleptic-induced extrapyramidal signs. Accurate diagnosis

is essential to safe treatment planning, as up to 50% of individuals with NCDLB have severe sensitivity to neuroleptic drugs, and these medications should be used with extreme

caution in managing the psychotic manifestations.

The diagnosis of mild NCDLB is appropriate for individuals who present with the core

or suggestive features at a stage when cognitive or functional impairments are not of sufficient severity to fulfill criteria for major NCD. However, as for all mild NCDs, there will

often be insufficient evidence to justify any single etiology, and use of the unspecified diagnosis is most appropriate.

Associated Features Supporting Diagnosis

Individuals with NCDLB frequently experience repeated falls and syncope and transient

episodes of unexplained loss of consciousness. Autonomic dysfunction, such as orthostatic hypotension and urinary incontinence, may be observed. Auditory and other

nonvisual hallucinations are common, as are systematized delusions, delusional misidentification, and depression.

Prevalence

The few population-based prevalence estimates for NCDLB available range from 0.1% to

5% of the general elderly population, and from 1.7% to 30.5% of all dementia cases. In

brain bank (autopsy) series, the pathological lesions known as Lewy bodies are present in

20%-35% of cases of dementia. The male-to-female ratio is approximately 1.5:1.

Development and Course

NCDLB is a gradually progressive disorder with insidious onset. However, there is often

a prodromal history of confusional episodes (delirium) of acute onset, often precipitated

by illness or surgery. The distinction between NCDLB, in which Lewy bodies are primarily cortical in location, and major or mild NCD due to Parkinson's disease, in which the pathology is primarily in the basal ganglia, is the order in which the cognitive and motor

symptoms emerge. In NCDLB, the cognitive decline is manifested early in the course of illness, at least a year before the onset of motor symptoms (see the section "Differential Di­

agnosis" for this disorder). Disease course may be characterized by occasional plateaus

but eventually progresses through severe dementia to death. Average duration of survival

is 5-7 years in clinical series. Onset of symptoms is typically observed from the sixth

through the ninth decades of life, with most cases having their onset when affected individuals are in their mid-70s.

Risk and Prognostic Factors

Genetic and physiological. Familial aggregation may occur, and several risk genes have

been identified, but in most cases of NCDLB, there is no family history.

Diagnostic iVlaricers

The underlying neurodegenerative disease is primarily a synucleinopathy due to alphasynuclein misfolding and aggregation. Cognitive testing beyond the use of a brief screening instrument may be necessary to define deficits clearly. Assessment scales developed to

measure fluctuation can be useful. The associated condition REM sleep behavior disorder

may be diagnosed through a formal sleep study or identified by questioning the patient or

informant about relevant symptoms. Neuroleptic sensitivity (challenge) is not recommended as a diagnostic marker but raises suspicion of NCDLB if it occurs. A diagnostically suggestive feature is low striatal dopamine transporter uptake on single photon

emission computed tomography (SPECT) or positron emission tomography (PET) scan.

Other clinically useful markers potentially include relative preservation of medial temporal structures on computed tomography (CT)/magnetic resonance imaging (MRI) brain

scan; reduced striatal dopamine transporter uptake on SPECT/PET scan; generalized low

uptake on SPECT/PET perfusion scan with reduced occipital activity; abnormal (low uptake) MIBG myocardial scintigraphy suggesting sympathetic denervation; and prominent

slow-wave activity on the electroencephalogram with temporal lobe transient waves.

Functional Consequences of iVlajor or iVliid

Neurocognitive Disorder With Lewy Bodies

Individuals with NCDLB are more functionally impaired than would be expected for their

cognitive deficits when contrasted to individuals with other neurodegenerative diseases,

such as Alzheimer's disease. This is largely a result of motor and autonomic impairments,

which cause problems with toileting, transferring, and eating. Sleep disorders and prominent psychiatric symptoms may also add to functional difficulties. Consequently, the quality of life of individuals with NCDLB is often significantly worse than that of individuals

with Alzheimer's disease.

Differential Diagnosis

Major or mild neurocognitive disorder due to Parkinson’s disease. A key differentiating feature in clinical diagnosis is the temporal sequence in which the parkinsonism and

the NCD appear. For NCD due to Parkinson's disease, the individual must develop cognitive decline in the context of established Parkinson's disease; by convention, the decline

should not reach the stage of major NCD until at least 1 year after Parkinson's is diagnosed.

If less than a year has passed since the onset of motor symptoms, the diagnosis is NCDLB.

This distinction is clearer at the major NCD level than at the mild NCD level.

The timing and sequence of parkinsonism and mild NCD may be more difficult to determine because the onset and clinical presentation can be ambiguous, and unspecified

mild NCD should be diagnosed if the other core and suggestive features are absent.

Comorbidity

Lewy body pathology frequently coexists with Alzheimer's disease and cerebrovascular

disease pathology, particularly among the oldest age groups. In Alzheimer's disease, there

is concomitant synuclein pathology in 60% of cases (if amygdala-restricted cases are included). In general, there is a higher rate of Lewy body pathology in individuals with dementia than in older individuals without dementia.

Major or Mild Vascular Neurocognitive Disorder

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. The clinical features are consistent with a vascular etiology, as suggested by either of

the following:

1. Onset of the cognitive deficits is temporally related to one or more cerebrovascular

events.

2. Evidence for decline is prominent in complex attention (including processing

speed) and frontal-executive function.

0. There is evidence of the presence of cerebrovascular disease from history, physical

examination, and/or neuroimaging considered sufficient to account for the neurocognitive deficits.

D. The symptoms are not better explained by another brain disease or systemic disorder.

Probable vascular neurocognitive disorder is diagnosed if one of the following is present; othenvise possible vascular neurocognitive disorder should be diagnosed:

1. Clinical criteria are supported by neuroimaging evidence of significant parenchymal injury attributed to cerebrovascular disease (neuroimaging-supported).

2. The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events.

3. Both clinical and genetic (e.g., cerebral autosomal dominant arteriopathy with subcortical

infarcts and leukoencephalopathy) evidence of cerebrovascular disease is present.

Possible vascular neurocognitive disorder is diagnosed if the clinical criteria are met

but neuroimaging is not available and the temporal relationship of the neurocognitive syndrome with one or more cerebrovascular events is not established.

Coding note: For probable major vascular neurocognitive disorder, with behavioral disturbance, code 290.40 (F01.51). For probable major vascular neurocognitive disorder,

without behavioral disturbance, code 290.40 (FOI .50). For possible major vascular neurocognitive disorder, with or without behavioral disturbance, code 331.9 (G31.9). An additional medical code for the cerebrovascular disease is not needed.

For mild vascular neurocognitive disorder, code 331.83 (G31.84). (Note: Do not use an

additional code for the vascular disease. Behavioral disturbance cannot be coded but

should still be indicated in writing.)

Diagnostic Features

The diagnosis of major or mild vascular neurocognitive disorder (NCD) requires the establishment of an NCD (Criterion A) and the determination that cerebrovascular disease is

the dominant if not exclusive pathology that accounts for the cognitive deficits (Criteria B

and C). Vaiscular etiology may range from large vessel stroke to microvascular disease; the

presentation is therefore very heterogeneous, stemming from the types of vascular lesions

and their extent and location. The lesions may be focal, multifocal, or diffuse and occur in

various combinations.

Many individuals with major or mild vascular NCD present with multiple infarctions,

with an acute stepwise or fluctuating decline in cognition, and intervening periods of

stability and even some improvement. Others may have gradual onset with slow progression, a rapid development of deficits followed by relative stability, or another complex

presentation. Major or mild vascular NCD with a gradual onset and slow progression is

generally due to small vessel disease leading to lesions in the white matter, basal ganglia,

and/or thalamus. The gradual progression in these cases is often punctuated by acute

events that leave subtle neurological deficits. The cognitive deficits in these cases can be attributed to disruption of cortical-subcortical circuits, and complex attention, particularly

speed of information processing, and executive ability are likely to be affected.

Assessing for the presence of sufficient cerebrovascular disease relies on history, physical examination, and neuroimaging (Criterion C). Etiological certainty requires the demonstration of abnormalities on neuroimaging. The lack of neuroimaging can result in

significant diagnostic inaccuracy by overlooking "silent" brain infarction and white matter lesions. However, if the neurocognitive impairment is temporally associated with one

or more well-documented strokes, a probable diagnosis can be made in the absence of neuroimaging. Clinical evidence of cerebrovascular disease includes documented history of

stroke, with cognitive decline temporally associated with the event, or physical signs consistent with stroke (e.g., hemiparesis; pseudobulbar syndrome, visual field defect). Neuroimaging (magnetic resonance imaging [MRI] or computed tomography [CT]) evidence of

cerebrovascular disease comprises one or more of the following: one or more large vessel

infarcts or hemorrhages, a strategically placed single infarct or hemorrhage (e.g., in angular gyrus, thalamus, basal forebrain), two or more lacunar infarcts outside the brain stem,

or extensive and confluent white matter lesions. The latter is often termed small vessel disease or subcortical ischemic changes on clinical neuroimaging evaluations.

For mild vascular NCD, history of a single stroke or extensive white matter disease is generally sufficient. For major vascular NCD, two or more strokes, a strategically placed stroke,

or a combination of white matter disease and one or more lacunes is generally necessary.

The disorder must not be better explained by another disorder. For example, prominent memory deficit early in the course might suggest Alzheimer's disease, early and

prominent parkinsonian features would suggest Parkinson's disease, and a close association between onset and depression would suggest depression.

Associated Features Supporting Diagnosis

A neurological assessment often reveals history of stroke and/or transient ischemic episodes, and signs indicative of brain infarctions. Also commonly associated are personality

and mood changes, abulia, depression, and emotional lability. The development of lateonset depressive symptoms accompanied by psychomotor slowing and executive dysfunction is a common presentation among older adults with progressive small vessel ischemic disease ("vascular depression").

Prevalence

Major or mild vascular NCD is the second most common cause of NCD after Alzheimer's

disease. In the United States, population prevalence estimates for vascular dementia range

from 0.2% in the 65-70 years age group to 16% in individuals 80 years and older. Within

3 months following stroke, 20%-30% of individuals are diagnosed with dementia. In neuropathology series, the prevalence of vascular dementia increases from 13% at age 70 years

to 44.6% at age 90 years or older, in comparison with Alzheimer's disease (23.6%-51%) and

combined vascular dementia and Alzheimer's disease (2%-46.4%). Higher prevalence has

been reported in African Americans compared with Caucasians, and in East Asian countries

(e.g., Japan, Chii;ia). Prevalence is higher in males than in females.

Development and Course

Major or mild vascular NCD can occur at any age, although the prevalence increases exponentially after age 65 years. In older individuals, additional pathologies may partly account for the neurocognitive deficits. The course may vary from acute onset with partial

improvement to stepwise decline to progressive decline, with fluctuations and plateaus of

varying durations. Pure subcortical major or mild vascular NCD can have a slowly progressive course that simulates major or mild NCD due to Alzheimer's disease.

Risk and Prognostic Factors

Environmental. The neurocognitive outcomes of vascular brain injury are influenced by

neuroplasticity factors such as education, physical exercise, and mental activity.

Genetic and physiological. The major risk factors for major or mild vascular NCD are the

same as those for cerebrovascular disease, including hypertension, diabetes, smoking, obesity,

high cholesterol levels, high homocysteine levels, other risk factors for atherosclerosis and arteriolosclerosis, atrial fibrillation, and other conditions increasing the risk of cerebral emboli.

Cerebral amyloid angiopathy is an important risk factor in which amyloid deposits occur

within arterial vessels. Another key risk factor is the hereditary condition cerebral autosomal

dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or CADASIL.

Diagnostic iVlarlcers

Structural neuroimaging, using MRI or CT, has an important role in the diagnostic process. There are no other established biomarkers of major or mild vascular NCD.

Functional Consequences of

Major or Mild Vascular Neurocognitive Disorder

Major or mild vascular NCD is commonly associated with physical deficits that cause additional disability.

Differential Diagnosis

Other neurocognitive disorders. Since incidental brain infarctions and white matter lesions are common in older individuals, it is important to consider other possible etiologies

when an NCD is present. A history of memory deficit early in the course, and progressive

worsening of memory, language, executive function, and perceptual-motor abilities in the

absence of corresponding focal lesions on brain imaging, are suggestive of Alzheimer's

disease as the primary diagnosis. Potential biomarkers currently being validated for Alzheimer's disease, such as cerebrospinal fluid levels of beta-amyloid and phosphorylated

tau, and amyloid imaging, may prove to be helpful in the differential diagnosis. NCD with

Lewy bodies is distinguished from major or mild vascular NCD by its core features of fluctuating cognition, visual hallucinations, and spontaneous parkinsonism. While deficits in

executive function and language occur in major or mild vascular NCD, the insidious onset

and gradual progression of behavioral features or language impairment are characteristic

of frontotemporal NCD and are not typical of vascular etiology.

Other medical conditions. A diagnosis of major or mild vascular NCD is not made if

other diseases (e.g., brain tumor, multiple sclerosis, encephalitis, toxic or metabolic disorders) are present and are of sufficient severity to account for the cognitive impairment.

Other mental disorders. A diagnosis of major or mild vascular NCD is inappropriate if

the symptoms can be entirely attributed to delirium, although delirium may sometimes be

superimposed on a preexisting major or mild vascular NCD, in which case both diagnoses

can be made. If the criteria for major depressive disorder are met and the cognitive impairment is temporally related to the likely onset of the depression, major or mild vascular

NCD should not be diagnosed. However, if the NCD preceded the development of the depression, or the severity of the cognitive impairment is out of proportion to the severity of

the depression, both should be diagnosed.

Comorbidity

Major or mild NCD due to Alzheimer's disease commonly co-occurs with major or mild

vascular NCD, in which case both diagnoses should be made. Major or mild vascular NCD

and depression frequently co-occur.

Major or Mild Neurocognitive Disorder

Due to Traumatic Brain Injury

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. There is evidence of a traumatic brain injury—that is, an impact to the head or other

mechanisms of rapid movement or displacement of the brain within the skull, with one

or more of the following:

1. Loss of consciousness.

2. Posttraumatic amnesia.

3. Disorientation and confusion.

4. Neurological signs (e.g., neuroimaging demonstrating injury; a new onset of seizures; a marked worsening of a preexisting seizure disorder; visual field cuts; anosmia; hemiparesis).

C. The neurocognitive disorder presents immediately after the occurrence of the traumatic brain injury or immediately after recovery of consciousness and persists past the

acute post-injury period.

Coding note: For major neurocognitive disorder due to traumatic brain injury, with behavioral

disturbance: For ICD-9-CM, first code 907.0 late effect of intracranial injury without skull fracture, followed by 294.11 major neurocognitive disorder due to traumatic brain injury, with behavioral disturbance. For ICD-10-CM, first code S06.2X9S diffuse traumatic brain injury with

loss of consciousness of unspecified duration, sequela; followed by F02.81 major neurocognitive disorder due to traumatic brain injury, with behavioral disturbance.

For major neurocognitive disorder due to traumatic brain injury, without behavioral disturbance: For ICD-9-CM, first code 907.0 late effect of intracranial injury without skull fracture,

followed by 294.10 major neurocognitive disorder due to traumatic brain injury, without behavioral disturbance. For ICD-10-CM, first code S06.2X9S diffuse traumatic brain injury with

loss of consciousness of unspecified duration, sequela; followed by F02.80 major neurocognitive disorder due to traumatic brain injury, without behavioral disturbance.

For mild neurocognitive disorder due to traumatic brain injury, code 331.83 (G31.84).

(Note: Do not use the additional code for traumatic brain injury. Behavioral disturbance

cannot be coded but should still be indicated in writing.)

Specifiers

Rate the severity of the neurocognitive disorder (NCD), not the underlying traumatic brain

injury (see the section "Development and Course" for this disorder).

Diagnostic Features

Major or mild NCD due to traumatic brain injury (TBI) is caused by an impact to the head,

or other mechanisms of rapid movement or displacement of the brain within the skull, as

can happen with blast injuries. Traumatic brain injury is defined as brain trauma with specific characteristics that include at least one of the following: loss of consciousness, posttraumatic amnesia, disorientation and confusion, or, in more severe cases, neurological

signs (e.g., positive neuroimaging, a new onset of seizures or a marked worsening of a preexisting seizure disorder, visual field cuts, anosmia, hemiparesis) (Criterion B). To be attributable to TBI, the NCD must present either immediately after the brain injury occurs or

immediately after the individual recovers consciousness after the injury and persist past

the acute post-injury period (Criterion C).

The cognitive presentation is variable. Difficulties in the domains of complex attention,

executive ability^, learning, and memory are common as well as slowing in speed of information processing and disturbances in social cognition. In more severe TBI in which there

is brain contusion, intracranial hemorrhage, or penetrating injury, there may be additional

neurocognitive deficits, such as aphasia, neglect, and constructional dyspraxia.

Associated Features Supporting Diagnosis

Major or mild NCD due to TBI may be accompanied by disturbances in emotional function

(e.g., irritability, easy frustration, tension and anxiety, affective lability); personality

changes (e.g., disinhibition, apathy, suspiciousness, aggression); physical disturbances

(e.g., headache, fatigue, sleep disorders, vertigo or dizziness, tinnitus or hyperacusis, photosensitivity, anosmia, reduced tolerance to psychotropic medications); and, particularly

in more severe TBI, neurological symptoms and signs (e.g., seizures, hemiparesis, visual

disturbances, cranial nerve deficits) and evidence of orthopedic injuries.

Prevaience

In the United States, 1.7 million TBIs occur annually, resulting in 1.4 million emergency department visits, 275,000 hospitalizations, and 52,000 deaths. About 2% of the population

lives with TBI-associated disability. Males account for 59% of TBIs in the United States.

The most common etiologies of TBI in the United States are falls, vehicular accidents, and

being struck on the head. Collisions and blows to the head that occur in the course of contact sports are increasingly recognized as sources of mild TBI, with a concern that repeated

mild TBI may have cumulatively persisting sequelae.

Deveiopment and Course

The severity of a TBI is rated at the time of injury/initial assessment as mild, moderate, or

severe according to the thresholds in Table 2.

The severity rating of the TBI itself does not necessarily correspond to the severity of

the resulting NCD. The course of recovery from TBI is variable, depending not only on the

specifics of the injury but also on cofactors, such as age, prior history of brain damage, or

substance abuse, that may favor or impede recovery.

TABLE 2 Severity ratings for traumatic brain injury

Injury characteristic Mild TBI Moderate TBI Severe TBI

Loss of consciousness <30 nnin 30 minutes-24 hours >24 hours

Posttraumatic amnesia <24 hours 24 hours-7 days >7 days

Disorientation and confusion 13-15 (not below 13 9-12 3-8

at initial assessment at 30 minutes)

(Glasgow Coma Scale

Score)

Neurobehavioral symptoms tend to be most severe in the immediate aftermath of the

TBI. Except in the case of severe TBI, the typical course is that of complete or substantial

improvement in associated neurocognitive, neurological, and psychiatric symptoms and

signs. Neurocognitive symptoms associated with mild TBI tend to resolve within days to

weeks after the injury with complete resolution typical by 3 months. Other symptoms that

may potentially co-occur with the neurological symptoms (e.g., depression, irritability,

fatigue, headache, photosensitivity, sleep disturbance) also tend to resolve in the weeks

following mild TBI. Substantial subsequent deterioration in these areas should trigger consideration of additional diagnoses. However, repeated mild TBI may be associated with

persisting neurocognitive disturbance.

With moderate and severe TBI, in addition to persistence of neurocognitive deficits,

there may be associated neurophysiological, emotional, and behavioral complications.

These include seizures (particularly in the first year), photosensitivity, h)φeracusis, irritability, aggression, depression, sleep disturbance, fatigue, apathy, inability to resume occupational and social functioning at pre-injury level, and deterioration in interpersonal

relationships. Moderate and severe TBI have been associated with increased risk of depression, aggression, and possibly neurodegenerative diseases such as Alzheimer's disease.

The features of persisting major or mild NCD due to TBI will vary by age, specifics of

the injury, and cofactors. Persisting TBI-related impairment in an infant or child may be reflected in delays in reaching developmental milestones (e.g., language acquisition), worse

academic performance, and possibly impaired social development. Among older teenagers and adults, persisting symptoms may include various neurocognitive deficits, irritability, hypersensitivity to light and sound, easy fatigability, and mood changes, including

depression, anxiety, hostility, or apathy. In older individuals with depleted cognitive reserve, mild TBI is more likely to result in incomplete recoveries.

Risk and Prognostic Factors

Risk factors for traumatic brain injury. Traumatic brain injury rates vary by age, with

the highest prevalence among individuals younger than 4 years, older adolescents, and individuals older than 65 years. Falls are the most common cause of TBI, with motor vehicle

accidents being second. Sports concussions are frequent causes of TBI in older children,

teenagers, and young adults.

Risk factors for neurocognitive disorder after traumatic brain injury. Repeated concussions can lead to persistent NCD and neuropathological evidence of traumatic encephalopathy. Co-occurring intoxication with a substance may increase the severity of a TBI

from a motor vehicle accident, but whether intoxication at the time of injury worsens neurocognitive outcome is unknown.

Course modifiers. Mild TBI generally resolves within a few weeks to months, although resolution may be delayed or incomplete in the context of repeated TBI. Worse outcome from

moderate to severe TBI is associated with older age (older than 40 years) and initial clinical parameters, such a^ low Glasgow Coma Scale score; worse motor function; pupillary nonreactivity; and computed tomography (CT) evidence of brain injury (e.g., petechial hemorrhages,

subarachnoid hemorrhage, midline shift, obliteration of third ventricle).

Diagnostic IViarlcers

Beyond neuropsychological testing, CT scanning may reveal petechial hemorrhages,

subarachnoid hemorrhage, or evidence of contusion. Magnetic resonance image scanning

may also reveal hyperintensities suggestive of microhemorrhages.

Functionai Consequences of iViajor or IViiid

Neurocognitive Disorder Due to Traumatic Brain injury

With mild NCD due to TBI, individuals may report reduced cognitive efficiency, difficulty

concentrating, and lessened ability to perform usual activities. With major NCD due to TBI, an

individual may have difficulty in independent living and self-care. Prominent neuromotor

features, such as severe incoordination, ataxia, and motor slowing, may be present in major

NCD due to TBI and may add to functional difficulties. Individuals with TBI histories report

more depressive symptoms, and these can amplify cognitive complaints and worsen functional outcome. Additionally, loss of emotional control, including aggressive or inappropriate

affect and apathy, may be present after more severe TBI with greater neurocognitive impairment. These features may compound difficulties with independent living and self-care.

Differentiai Diagnosis

In some instances, severity of neurocognitive symptoms may appear to be inconsistent

with the severity of the TBI. After previously undetected neurological complications (e.g.,

chronic hematoma) are excluded, the possibility of diagnoses such as somatic symptom

disorder or factitious disorder need to be considered. Posttraumatic stress disorder (PTSD)

can co-occur with the NCD and have overlapping symptoms (e.g., difficulty concentrating, depressed mood, aggressive behavioral disinhibition).

Comorbidity

Among individuals with substance use disorders, the neurocognitive effects of the substance contribute to or compound the TBI-associated neurocognitive change. Some symptoms associated with TBI may overlap with symptoms found in cases of PTSD, and the two

disorders may co-occur, especially in military populations.

Substance/Medication-Induced

Major or Mild Neurocognitive Disorder

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. The neurocognitive impairments do not occur exclusively during the course of a delirium and persist beyond the usual duration of intoxication and acute withdrawal.

C. The involved substance or medication and duration and extent of use are capable of

producing the neurocognitive impairment.

D. The temporal course of the neurocognitive deficits is consistent with the timing of substance or medication use and abstinence (e.g., the deficits remain stable or improve

after a period of abstinence).

E. The neurocognitive disorder is not attributable to another medical condition or is not

better explained by another mental disorder.

Coding note: The ICD-9-CM and ICD-10-CM codes for the [specific substance/medication]-induced neurocognitive disorders are indicated in the table below. Note that the ICD10-CM code depends on whether or not there is a comorbid substance use disorder present

for the same class of substance. If a mild substance use disorder is comorbid with the substance-induced neurocognitive disorder, the 4th position character is “1 and the clinician

should record “mild [substance] use disorder” before the substance-induced neurocognitive

disorder (e.g., “mild inhalant use disorder with inhalant-induced major neurocognitive disorder”). If a moderate or severe substance use disorder is comorbid with the substanceinduced neurocognitive disorder, the 4th position character is “2,” and the clinician should

record “moderate [substance] use disorder” or “severe [substance] use disorder,” depending

on the severity of the comorbid substance use disorder. If there is no comorbid substance

use disorder, then the 4th position character is “9,” and the clinician should record only the

substance-induced neurocognitive disorder. For some classes of substances (i.e., alcohol;

sedatives, hypnotics, anxiolytics), it is not permissible to code a comorbid mild substance

use disorder with a substance-induced neurocognitive disorder; only a comorbid moderate

or severe substance use disorder, or no substance use disorder, can be diagnosed. Behavioral disturbance cannot be coded but should still be indicated in writing.

ICD-10-CM

ICD-9-CM

With use

disorder,

mild

With use

disorder,

moderate or

severe

Without use

disorder

Alcohol (major neurocognitive

disorder), nonamnesticconfabulatory type

291.2 NA FI 0.27 FI 0.97

Alcohol (major neurocognitive

disorder), amnesticconfabulatory type

291.1 NA FI 0.26 FI 0.96

Alcohol (mild neurocognitive

disorder)

291.89 NA FI 0.288 FI 0.988

Inhalant (major neurocognitive

disorder)

292.82 F18.17 FI 8.27 FI 8.97

Inhalant (mild neurocognitive

disorder)

292.89 FI 8.188 FI 8.288 FI 8.988

Sedative, hypnotic, or anxiolytic

(major neurocognitive disorder)

292.82 NA FI 3.27 FI 3.97

Sedative, hypnotic, or anxiolytic

(mild neurocognitive disorder)

292.89 NA FI 3.288 FI 3.988

Other (or unknown) substance

(major neurocognitive disorder)

292.82 F19.17 FI 9.27 FI 9.97

Other (or unknown) substance

(mild neurocognitive disorder)

292.89 F19.188 FI 9.288 FI 9.988

Specify if:

Persistent:,Neurocognitive impairment continues to be significant after an extended

period of abstinence.

Recording Procedures

ICD-9-CM. The name of the substance/medication-induced neurocognitive disorder begins with the specific substance/medication (e.g., alcohol) that is presumed to be causing

the neurocognitive symptoms. The diagnostic code is selected from the table included in

the criteria set, which is based on the drug class. For substances that do not fit into any of

the classes, the code for "other substance" should be used; and in cases in which a substance

is judged to be an etiological factor but the specific class of substance is unknown, the category "unknown substance" should be used.

The name of the disorder (i.e., [specific substance]-induced major neurocognitive disorder or [specific substance]-induced mild neurocognitive disorder) is followed by the

type in the case of alcohol (i.e., nonamnestic-confabulatory type, amnestic-confabulatory

type), followed by specification of duration (i.e., persistent). Unlike the recording procedures

for ICD-IO-CM, which combine the substance/medication-induced disorder and substance use disorder into a single code, for ICD-9-CM a separate diagnostic code is given for

the substance use disorder. For example, in the case of persistent amnestic-confabulatory

symptoms in a man with a severe alcohol use disorder, the diagnosis is 291.1 alcoholinduced major neurocognitive disorder, amnestic-confabulatory type, persistent. An additional diagnosis of 303.90 severe alcohol use disorder is also given. If the substance/medication-induced neurocognitive disorder occurs without a comorbid substance use disorder

(e.g., after a sporadic heavy use of inhalants), no accompanying substance use disorder is

noted (e.g., 292.82 inhalant-induced mild neurocognitive disorder).

ICD-10-CM. The name of the substance/medication-induced neurocognitive disorder

begins with the specific substance (e.g., alcohol) that is presumed to be causing the neurocognitive symptoms. The diagnostic code is selected from the table included in the criteria

set, which is based on the drug class and presence or absence of a comorbid substance use

disorder. For substances that do not fit into any of the classes, the code for "other substance" should be used; and in cases in which a substance is judged to be an etiological factor but the specific class of substance is unknown, the category "unknown substance"

should be used.

When recording the name of the disorder, the comorbid substance use disorder (if any) is

listed first, followed by the word "with," followed by the name of the disorder (i.e., [specific

substance]-induced major neurocognitive disorder or [specific substance]-induced mild

neurocognitive disorder), followed by the type in the case of alcohol (i.e., nonamnestic-confabulatory type, amnestic-confabulatory type), followed by specification of duration (i.e.,

persistent). For example, in the case of persistent amnestic-confabulatory symptoms in a

man with a severe alcohol use disorder, the diagnosis is F10.26 severe alcohol use disorder

with alcohol-induced major neurocognitive disorder, amnestic-confabulatory type, persistent. A separate diagnosis of the comorbid severe alcohol use disorder is not given. If the

substance-induced neurocognitive disorder occurs without a comorbid substance use disorder (e.g., after a sporadic heavy use of inhalants), no accompanying substance use disorder is noted (e.g., F18.988 inhalant-induced mild neurocognitive disorder).

Diagnostic Features

Substance/medication-induced major or mild NCD is characterized by neurocognitive

impairments that persist beyond the usual duration of intoxication and acute withdrawal

(Criterion B). Initially, these manifestations can reflect slow recovery of brain functions

from a period of prolonged substance use, and improvements in neurocognitive as well as

brain imaging indicators may be seen over many months. If the disorder continues for an

extended period, persistent should be specified. The given substance and its use must be

known to be capable of causing the observed impairments (Criterion C). While nonspecific

decrements in a range of cognitive abilities can occur with nearly any substance of abuse

and a variety of medications, some patterns occur more frequently with selected drug

classes. For example, NCD due to sedative, hypnotic, or anxiolytic drugs (e.g., benzodiazepines, barbiturates) may show greater disturbances in memory than in other cognitive

functions. NCD induced by alcohol frequently manifests with a combination of impairments in executive-function and memory and learning domains. The temporal course of

the substance-induced NCD must be consistent with that of use of the given substance

(Criterion D). In alcohol-induced amnestic confabulatory (Korsakoff's) NCD, the features

include prominent amnesia (severe difficulty learning new information with rapid forgetting) and a tendency to confabulate. These manifestations may co-occur with signs of thiamine encephalopathy (Wernicke's encephalopathy) with associated features such as

nystagmus and ataxia. Ophthalmoplegia of Wernicke's encephalopathy is typically characterized by a lateral gaze paralysis.

In addition to or independent of the more common neurocognitive symptoms related

to methamphetamine use (e.g., difficulties with learning and memory; executive function), methamphetamine use can also be associated with evidence of vascular injury (e.g.,

focal weakness, unilateral incoordination, asymmetrical reflexes). The most common neurocognitive profile approximates that seen in vascular NCD.

Associated Features Supporting Diagnosis

Intermediate-duration NCD induced by drugs with central nervous system depressant effects

may manifest with added symptoms of increased irritability, anxiety, sleep disturbance, and

dysphoria. Intermediate-duration NCD induced by stimulant drugs may manifest with rebound depression, hypersomnia, and apathy. In severe forms of substance/medicationinduced major NCD (e.g., associated with long-term alcohol use), there may be prominent

neuromotor features, such as incoordination, ataxia, and motor slowing. There may also be

loss of emotional control, including aggressive or inappropriate affect, or apathy.

Prevalence

The prevalence of these conditions is not known. Prevalence figures for substance abuse are

available, and substance/medication-induced major or mild NCDs are more likely in those

who are older, have longer use, and have other risk factors such as nutritional deficits.

For alcohol abuse, the rate of mild NCD of intermediate duration is approximately 30%-

40% in the first 2 months of abstinence. Mild NCD may persist, particularly in those who do

not achieve stable abstinence until after age 50 years. Major NCD is rare and may result from

concomitant nutritional deficits, as in alcohol-induced amnestic confabulatory NCD.

For individuals quitting cocaine, methamphetamine, opioids, phencyclidine, and sedative, hypnotics, or anxiolytics, substance/medication-induced mild NCD of intermediate

duration may occur in one-third or more, and there is some evidence that these substances

may also be associated with persistent mild NCD. Major NCD associated with these substances is rare, if it occurs at all. In the case of methamphetamine, cerebrovascular disease

can also occur, resulting in diffuse or focal brain injury that can be of mild or major neurocognitive levels. Solvent exposure has been linked to both major and mild NCD of both

intermediate and persistent duration.

The presence of NCD induced by cannabis and various hallucinogens is controversial.

With cannabis, intoxication is accompanied by various neurocognitive disturbances, but

these tend to clear with abstinence.

Development and Course

Substance use disorders tend to commence during adolescence and peak in the 20s and

30s. Although longer history of severe substance use disorder is associated with greater

likelihood of NCD, the relationships are not straightforward, with substantial and even

complete recovery of neurocognitive functions being common among individuals who

achieve stable abstinence prior to age 50 years. Substance/medication-induced major or

mild NCD is most likely to become persistent in individuals who continue abuse of substances past age 50 years, presumably because of a combination of lessened neural plasticity and beginnings of other age-related brain changes. Earlier commencement of abuse,

particularly of alcohol, may lead to defects in later neural development (e.g., later stages of

maturation of frontal circuitries), which may have effects on social cognition as well as

other neurocognitive abilities. For alcohol-induced NCD, there may be an additive effect

of aging and alcohol-induced brain injury.

Risk and Prognostic Factors

Risk factors for substance/medication-induced NCDs include older age, longer use, and

persistent use past age 50 years. In addition, for alcohol-induced NCD, long-term nutritional deficiencies, liver disease, vascular risk factors, and cardiovascular and cerebrovascular disease may contribute to risk.

Diagnostic iViaricers

Magnetic resonance imaging (MRI) of individuals with chronic alcohol abuse frequently

reveals cortical thinning, white matter loss, and enlargement of sulci and ventricles. While

neuroimaging abnormalities are more common in those with NCDs, it is possible to observe NCDs without neuroimaging abnormalities, and vice versa. Specialized techniques

(e.g., diffusion tensor imaging) may reveal damage to specific white matter tracts. Magnetic resonance spectroscopy may reveal reduction in N-acetylaspartate, and increase in

markers of inflammation (e.g., myoinositol) or white matter injury (e.g., choline). Many of

these brain imaging changes and neurocognitive manifestations reverse following successful abstinence. In individuals with methamphetamine use disorder, MRI may also reveal hyperintensities suggestive of microhemorrhages or larger areas of infarction.

Functional Consequences of Substance/lVledicationinduced iViajor or iVliid Neurocognitive Disorder

The functional consequences of substance/medication-induced mild NCD are sometimes

augmented by reduced cognitive efficiency and difficulty concentrating beyond that seen

in many other NCDs. In addition, at both major and mild levels, substance/medicationinduced NCDs may have associated motor syndromes that increase the level of functional

impairment.

Differential Diagnosis

Individuals with substance use disorders, substance intoxication, and substance withdrawal

are at increased risk for other conditions that may independently, or through a compounding

effect, result in neurocognitive disturbance. These include history of traumatic brain injury

and infections that can accompany substance use disorder (e.g., MV, hepatitis C virus, syphilis). Therefore, presence of substance/medication-induced major or mild NCD should be

differentiated from NCDs arising outside the context of substance use, intoxication, and withdrawal, including these accompanying conditions (e.g., traumatic brain injury).

Comorbidity

Substance use disorders, substance intoxication, and substance withdrawal are highly comorbid with other mental disorders. Comorbid posttraumatic stress disorder, psychotic

disorders, depressive and bipolar disorders, and neurodevelopmental disorders can contribute to neurocognitive impairment in substance users. Traumatic brain injury occurs

more frequently with substance use, complicating efforts to determine the etiology of NCD

in such cases. Severe, long-term alcohol use disorder can be associated with major organ

system disease, including cerebrovascular disease and cirrhosis. Amphetamine-induced

NCD may be accompanied by major or mild vascular NCD, also secondary to amphetamine use.

Major or Mild Neurocognitive Disorder

Due to HIV Infection

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. Tliere is documented infection witfi human immunodeficiency virus (HIV).

C. The neurocognitive disorder is not better explained by non-HIV conditions, including

secondary brain diseases such as progressive multifocal leukoencephalopathy or

cryptococcal meningitis.

D. The neurocognitive disorder is not attributable to another medical condition and is not

better explained by a mental disorder.

Coding note: For major neurocognitive disorder due to HIV infection, with behavioral disturbance, code first 042 (B20) HIV infection, followed by 294.11 (F02.81) major neurocognitive disorder due to HIV infection, with behavioral disturbance. For major neurocognitive

disorder due to HIV infection, without behavioral disturbance, code first 042 (820) HIV infection, followed by 294.10 (F02.80) major neurocognitive disorder due to HIV infection,

without behavioral disturbance.

For mild neurocognitive disorder due to HIV infection, code 331.83 (G31.84). (Note: Do

not use the additional code for HIV infection. Behavioral disturbance cannot be coded but

should still be indicated in writing.)

Diagnostic Features

HIV disease is caused by infection with human immunodeficiency virus type-1 (HIV-1),

which is acquired through exposure to bodily fluids of an infected person through injection

drug use, unprotected sexual contact, or accidental or iatrogenic exposure (e.g., contaminated blood supply, needle puncture injury to medical personnel). HIV infects several types

of cells, most particularly immune cells. Over time, the infection can cause severe depletion

of "T-helper" (CD4) lymphocytes, resulting in severe immunocompromise, often leading to

opportunistic infections and neoplasms. This advanced form of HIV infection is termed

acquired immune deficiency syndrome (AIDS). Diagnosis of HIV is confirmed by established

laboratory methods such as enzyme-linked immunosorbent assay for HIV antibody with

Western blot confirmation and/or polymerase chain reaction-based assays for HIV.

Some individuals with HIV infection develop an NCD, which generally shows a "subcortical pattern" with prominently impaired executive function, slowing of processing

speed, problems with more demanding attentional tasks, and difficulty in learning new

information, but fewer problems with recall of learned information. In major NCD, slowing may be prominent. Language difficulties, such as aphasia, are uncommon, although

reductions in fluency may be observed. HIV pathogenic processes can affect any part of

the brain; therefore, other patterns are possible.

Associated Features Supporting Diagnosis

Major or mild NCD due to HIV infection is usually more prevalent in individuals with

prior episodes of severe immunosuppression, high viral loads in the cerebrospinal fluid,

and indicators of advanced HIV disease such as anemia and hypoalbuminemia. Individuals with advanced NCD may experience prominent neuromotor features such as severe

incoordination, ataxia, and motor slowing. There may be loss of emotional control, including aggressive or inappropriate affect or apathy.

Prevaience

Depending on stage of HIV disease, approximately one-third to over one-half of HIVinfected individuals have at least mild neurocognitive disturbance, but some of these disturbances may not meet the full criteria for mild NCD. An estimated 25% of individuals

with HIV will have signs and symptoms that meet criteria for mild NCD, and in fewer than

5% would criteria for major NCD be met.

Development and Course

An NCD due to HIV infection can resolve, improve, slowly worsen, or have a fluctuating

course. Rapid progression to profound neurocognitive impairment is uncommon in the

context of currently available combination antiviral treatment; consequently, an abrupt

change in mental status in an individual with HIV may prompt an evaluation of other

medical sources for the cognitive change, including secondary infections. Because HIV infection preferentially affects subcortical regions over the course of illness, including deep

white matter, the progression of the disorder follows a "subcortical" pattern. Since HIV

can affect a variety of brain regions, and the illness can take on many different trajectories

depending on associated comorbidities and consequences of HIV, the overall course of an

NCD due to HIV infection has considerable heterogeneity. A subcortical neurocognitive

profile may interact with age over the life course, when psychomotor slowing and motor

impairments such as slowed gait may occur as a consequence of other age-related conditions so that the overall progression may appear more pronounced in later life.

In developed countries, HIV disease is primarily a condition of adults, with acquisition

via risky behaviors (e.g., unprotected sex, injection drug use) beginning in late adolescence

and peaking during young and middle adulthood. In developing countries, particularly

sub-Saharan Africa, where HIV testing and antiretroviral treatments for pregnant women

are not readily available, perinatal transmission is common. The NCD in such infants and

children may present primarily as neurodevelopmental delay. As individuals treated for

HIV survive into older age, additive and interactive neurocognitive effects of HIV and

aging, including other NCDs (e.g., due to Alzheimer's disease, due to Parkinson's disease), are possible.

R is k and Prognostic Factors

Risk and prognostic factors for HIV infection. Risk factors for HIV infection include injection drug use, unprotected sex, and unprotected blood supply and other iatrogenic factors.

Risk and prognostic factors for major or mild neurocognitive disorder due to HIV infection. Paradoxically, NCD due to HIV infection has not declined significantly with the

advent of combined antiretroviral therapy, although the most severe presentations (consistent with the diagnosis of major NCD) have decreased sharply. Contributory factors

may include inadequate control of HIV in the central nervous system (CNS), the evolution

of drug-resistant viral strains, the effects of chronic long-term systemic and brain inflammation, and the effects of comorbid factors such as aging, drug abuse, past history of CNS

trauma, and co-infections, such as with the hepatitis C virus. Chronic exposure to antiretroviral drugs also raises the possibility of neurotoxicity, although this has not been definitively established.

Diagnostic iViaricers

Serum HIV testing is required for the diagnosis. In addition, HIV characterization of the cerebrospinal fluid may be helpful if it reveals a disproportionately high viral load in cerebrospinal

fluid versus in the plasma. Neuroimaging (i.e., magnetic resonance imaging [MRI]) may reveal

reduction in total brain volume, cortical thinning, reduction in white matter volume, and

patchy areas of abnormal white matter (hyperintensities). MRI or lumbar puncture may be

helpful to exclude a specific medical condition such as cryptococcus infection or herpes encephalitis that may contribute to CNS changes in the context of AIDS. Specialized techniques

such as diffusion tensor imaging may reveal damage to specific white matter tracts.

Functionai Consequences of iVlajor or iVliid

Neurocognitive Disorder Due to HIV infection

Functional consequences of major or mild NCD due to HIV infection are variable across

individuals. Thus, impaired executive abilities and slowed information processing may

substantially interfere with the complex disease management decisions required for adherence to the combined antiretroviral therapy regimen. The likelihood of comorbid disease may further create functional challenges.

Differentiai Diagnosis

In the presence of comorbidities, such as other infections (e.g., hepatitis C virus, syphilis),

drug abuse (e.g., methamphetamine abuse), or prior head injury or neurodevelopmental

conditions, major or mild NCD due to HIV infection can be diagnosed provided there is evidence that infection with HIV has worsened any NCDs due to such preexisting or comorbid

conditions. Among older adults, onset of neurocognitive decline related to cerebrovascular

disease or neurodegeneration (e.g., major or mild NCD due to Alzheimer's disease) may

need to be differentiated. In general, stable, fluctuating (without progression) or improving

neurocognitive status would favor an HIV etiology, whereas steady or stepwise deterioration would suggest neurodegenerative or vascular etiology. Because more severe immunodeficiency can result in opportunistic infections of the brain (e.g., toxoplasmosis;

cryptococcosis) and neoplasia (e.g., CNS lymphoma), sudden onset of an NCD or sudden

worsening of that disorder demands active investigation of non-HIV etiologies.

Comorbidity

HIV disease is accompanied by chronic systemic and neuro-inflammation that can be associated with cerebrovascular disease and metabolic syndrome. These complications can

be part of the pathogenesis of major or mild NCD due to HIV infection. HIV frequently cooccurs with conditions such as substance use disorders when the substance has been injected and other sexually transmitted disorders.

Major or Mild Neurocognitive Disorder

Due to Prion Disease

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. There is insidious onset, and rapid progression of impairment is common.

C. There are motor features of prion disease, such as myoclonus or ataxia, or biomarker

evidence.

D. The neurocognitive disorder is not attributable to another medical condition and is not

better expiated by another mental disorder.

Coding note: For major neurocognitive disorder due to prion disease, with behavioral disturbance, code first 046.79 (A81.9) prion disease, followed by 294.11 (F02.81) major

neurocognitive disorder due to prion disease, with behavioral disturbance. For major neurocognitive disorder due to prion disease, without behavioral disturbance, code first

046.79 (A81.9) prion disease, followed by 294.10 (F02.80) major neurocognitive disorder

due to prion disease, without behavioral disturbance.

For mild neurocognitive disorder due to prion disease, code 331.83 (G31.84). (Note: Do

not use the additional code for prion disease. Behavioral disturbance cannot be coded but

should still be indicated in writing.)

Diagnostic Features

The classification of major or mild neurocognitive disorder (NCD) due to prion disease includes NCDs due to a group of subacute spongiform encephalopathies (including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, kuru, Gerstmann-SträusslerScheinker syndrome, and fatal insomnia) caused by transmissible agents known as prions.

The most common type is sporadic Creutzfeldt-Jakob disease, typically referred to as

Creutzfeldt-Jakob disease (CJD). Variant CJD is much rarer and is associated with transmission of bovine spongiform encephalopathy, also called "mad cow disease." Typically,

individuals with CJD present with neurocognitive deficits, ataxia, and abnormal movements such as myoclonus, chorea, or dystonia; a startle reflex is also common. Typically,

the history reveals rapid progression to major NCD over as little as 6 months, and thus the

disorder is typically seen only at the major level. However, many individuals with the disorder may have atypical presentations, and the disease can be confirmed only by biopsy or

at autopsy. Individuals with variant CJD may present with a greater preponderance of

psychiatric symptoms, characterized a by low mood, withdrawal, and anxiety. Prion disease is typically not diagnosed without at least one of the characteristic biomarker features: recognized lesions on magnetic resonance imaging with DWI (diffusion-weighted

imaging) or FLAIR (fluid-attenuated inversion recovery), tau or 14-3-3 protein in cerebrospinal fluid, characteristic triphasic waves on electroencephalogram, or, for rare familial

forms, family history or genetic testing.

Prevaience

The annual incidence of sporadic CJD is approximately one or two cases per million people. Prevalence is unknown but very low given the short survival.

Development and Course

Prion disease may develop at any age in adults—the peak age for the sporadic CJD is approximately 67 years—although it has been reported to occur in individuals spaniüng the

teenage years to late life. Prodromal symptoms of prion disease may include fatigue, anxiety, problems with appetite or sleeping, or difficulties with concentration. After several

weeks, these symptoms may be followed by incoordination, altered vision, or abnormal

gait or other movements that may be myoclonic, choreoathetoid, or ballistic, along with a

rapidly progressive dementia. The disease typically progresses very rapidly to the major

level of impairment over several months. More rarely, it can progress over 2 years and appear similar in its course to other NCDs.

Risk Factors and Prognosis

Environmental. Cross-species transmission of prion infections, with agents that are

closely related to the human form, has been demonstrated (e.g., the outbreak of bovine

spongiform encephalopathy inducing variant CJD in the United Kingdom during the mid1990s). Transmission by comeal transplantation and by human growth factor injection has

been documented, and anecdotal cases of transmission to health care workers have been

reported.

Genetic and physiological. There is a genetic component in up to 15% of cases, associated with an autosomal dominant mutation.

Diagnostic iVlarlcers

Prion disease can be definitively confirmed only by biopsy or at autopsy. Although there are

no distinctive findings on cerebrospinal fluid analysis across the prion diseases, reliable biomarkers are being developed and include 14-3-3 protein (particularly for sporadic CJD) as

well as tau protein. Magnetic resonance brain imaging is currently considered the most sensitive diagnostic test when DWI is performed, with the most common finding being multifocal gray matter hyperintensities in subcortical and cortical regions. In some individuals,

the electroencephalogram reveals periodic sharp, often triphasic and synchronous discharges at a rate of 0.5-2 Hz at some point during the course of the disorder.

Differential Diagnosis

Other major neurocognitive disorders. Major NCD due to prion disease may appear

similar in its course to other NCDs, but prion diseases are typically distinguished by their

rapid progression and prominent cerebellar and motor symptoms.

Major or Mild Neurocognitive Disorder

Due to Parkinson’s Disease

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. The disturbance occurs in the setting of established Parkinson’s disease.

C. There is insidious onset and gradual progression of impairment.

D. The neurocognitive disorder is not attributable to another medical condition and is not

better explained by another mental disorder.

Major or mild neurocognitive disorder probably due to Parkinson’s disease should

be diagnosed if 1 and 2 are both met. iUlajor or miid neurocognitive disorder possibly

due to Parltinson’s disease should be diagnosed if 1 or 2 is met:

1. There is no evidence of mixed etiology (i.e., absence of other neurodegenerative or

cerebrovascular disease or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).

2. The Parkinson’s disease clearly precedes the onset of the neurocognitive disorder.

Coding note: For major neurocognitive disorder probably due to Parkinson’s disease,

with behavioral disturbance, code first 332.0 (G20) Parkinson’s disease, followed by

294.11 (F02.81) major neurocognitive disorder probably due to Parkinson’s disease, with

behavioral disturbance. For major neurocognitive disorder probably due to Parkinson’s

disease, without behavioral disturbance, code first 332.0 (G20) Parkinson’s disease, fol­

lowed by 294.10 (F02.80) major neurocognitive disorder probably due to Parkinson’s disease, without be^havioral disturbance.

For major neurocognitive disorder possibly due to Parkinson’s disease, code 331.9

(G31.9) major neurocognitive disorder possibly due to Parkinson’s disease. (Note: Do not

use the additional code for Parkinson’s disease. Behavioral disturbance cannot be coded

but should still be indicated in writing.)

For mild neurocognitive disorder due to Parkinson’s disease, code 331.83 (G31.84).

(Note: Do not use the additional code for Parkinson’s disease. Behavioral disturbance

cannot be coded but should still be indicated in writing.)

Diagnostic Features

The essential feature of major or mild neurocognitive disorder (NCD) due to Parkinson's

disease is cognitive decline following the onset of Parkinson's disease. The disturbance

must occur in the setting of established Parkinson's disease (Criterion B), and deficits must

have developed gradually (Criterion C). The NCD is viewed as probably due to Parkinson's

disease when there is no evidence of another disorder that might be contributing to the

cognitive decline and when the Parkinson's disease clearly precedes onset of the NCD. The

NCD is considered possibly due to Parkinson's disease either when there is no evidence of

another disorder that might be contributing to the cognitive decline or when the Parkinson's disease precedes onset of the NCD, but not both.

Associated Features Supporting Diagnosis

Frequently present features include apathy, depressed mood, anxious mood, hallucinations, delusions, personality changes, rapid eye movement sleep behavior disorder, and

excessive daytime sleepiness.

Prevaience

The prevalence of Parkinson's disease in the United States steadily increases with age from

approximately 0.5% between ages 65 and 69 to 3% at age 85 years and older. Parkinson's

disease is more common in males than in females. Among individuals with Parkinson's

disease, as many as 75% will develop a major NCD sometime in the course of their disease.

The prevalence of mild NCD in Parkinson's disease has been estimated at 27%.

Deveiopment and Course

Onset of Parkinson's disease is typically between the sixth and ninth decades of life, with

most expression in the early 60s. Mild NCD often develops relatively early in the course of

Parkinson's disease, whereas major impairment typically does not occur until late.

Risic and Prognostic Factors

Environmental. Risk factors for Parkinson's disease include exposure to herbicides and

pesticides.

Genetic and physiological. Potential risk factors for NCD among individuals with Parkinson's disease include older age at disease onset and increasing duration of disease.

Diagnostic iVlaricers

Neuropsychological testing, with a focus on tests that do not rely on motor function, is critical in detecting the core cognitive deficits, particularly at the mild NCD phase. Structural

neuroimaging and dopamine transporter scans, such as DaT scans, may differentiate

Lewy body-related dementias (Parkinson's and dementia with Lewy bodies) from non-

Lewy body-related dementias (e.g., Alzheimer's disease) and can sometimes be helpful in

the evaluation of major or mild NCD due to Parkinson's disease.

Differential Diagnosis

Major or mild neurocognitive disorder with Lewy bodies. This distinction is based substantially on the timing and sequence of motor and cognitive symptoms. For NCD to be attributed to Parkinson's disease, the motor and other symptoms of Parkinson's disease must

be present well before (by convention, at least 1 year prior) cognitive decline has reached

the level of major NCD, whereas in major or mild NCD with Lewy bodies, cognitive symptoms begin shortly before, or concurrent with, motor symptoms. For mild NCD, the timing

is harder to establish because the diagnosis itself is less clear and the two disorders exist on

a continuum. Unless Parkinson's disease has been established for some time prior to the

onset of cognitive decline, or typical features of major or mild NCD with Lewy bodies are

present, it is preferable to diagnose unspecified mild NCD.

Major or mild neurocognitive disorder due to Alzheimer’s disease. The motor features

are the key to distinguishing major or mild NCD due to Parkinson's disease from major or

mild NCD due to Alzheimer's disease. However, the two disorders can co-occur.

Major or mild vascular neurocognitive disorder. Major or mild vascular NCD may present with parkinsonian features such as psychomotor slowing that may occur as a consequence of subcortical small vessel disease. However, the parkinsonian features typically

are not sufficient for a diagnosis of Parkinson's disease, and the course of the NCD usually

has a clear association with cerebrovascular changes.

Neurocognitive disorder due to another medical condition (e.g., neurodegenerative

disorders). When a diagnosis of major or mild NCD due to Parkinson's disease is being

considered, the distinction must also be made from other brain disorders, such as progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, tumors, and

hydrocephalus.

Neuroleptic-induced parkinsonism. Neuroleptic-induced parkinsonism can occur in

individuals with other NCDs, particularly when dopamine-blocking drugs are prescribed

for the behavioral manifestations of such disorders

Other medical conditions. Delirium and NCDs due to side effects of dopamine-blocking

drugs and other medical conditions (e.g., sedation or impaired cognition, severe hypothyroidism, Bi2 deficiency) must also be ruled out.

Comorbidity

Parkinson's disease may coexist with Alzheimer's disease and cerebrovascular disease, especially in older individuals. The compounding of multiple pathological features may diminish

the functional abilities of individuals with Parkinson's disease. Motor symptoms and frequent

co-occurrence of depression or apathy can make functional impairment worse.

Major or Mild Neurocognitive Disorder

Due to Huntington’s Disease

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. There is insidious onset and gradual progression.

C. There is clinically established Huntington’s disease, or risk for Huntington’s disease

based on family history or genetic testing.

D. The neurocognitive disorder is not attributable to another medical condition and is not

better explained by another mental disorder.

Coding note: For major neurocognitive disorder due to Huntington’s disease, with behavioral disturbance, code first 333.4 (G10) Huntington’s disease, followed by 294.11

(F02.81) major neurocognitive disorder due to Huntington’s disease, with behavioral disturbance. For major neurocognitive disorder due to Huntington’s disease, without behavioral disturbance, code first 333.4 (G10) Huntington’s disease, followed by 294.10 (F02.80)

major neurocognitive disorder due to Huntington’s disease, without behavioral disturbance.

For mild neurocognitive disorder due to Huntington’s disease, code 331.83 (G31.84).

(Note: Do not use the additional code for Huntington’s disease. Behavioral disturbance

cannot be coded but should still be indicated in writing.)

Diagnostic Features

Progressive cognitive impairment is a core feature of Huntington's disease, with early changes

in executive function (i.e., processing speed, organization, and planning) rather than learning and memory. Cognitive and associated behavioral changes often precede the emergence

of the typical motor abnormalities of bradykinesia (i.e., slowing of voluntary movement)

and chorea (i.e., involuntary jerking movements). A diagnosis of definite Huntington's disease is given in the presence of unequivocal, extrapyramidal motor abnormalities in an individual with either a family history of Huntington's disease or genetic testing showing a

CAG trinucleotide repeat expansion in the HIT gene, located on chromosome 4.

Associated Features Supporting Diagnosis

Depression, irritability, anxiety, obsessive-compulsive symptoms, and apathy are frequently, and psychosis more rarely, associated with Huntington's disease and often precede the onset of motor symptoms.

Prevaience

Neurocognitive deficits are an eventual outcome of Huntington's disease; the worldwide

prevalence is estimated to be 2.7 per 100,000. The prevalence of Huntington's disease in

North America, Europe, and Australia is 5.7 per 100,000, with a much lower prevalence of

0.40 per 100,000 in Asia.

Deveiopment and Course

The average age at diagnosis of Huntington's disease is approximately 40 years, although

this varies widely. Age at onset is inversely correlated with CAG expansion length. Juvenile Huntington's disease (onset before age 20) may present more commonly with bradykinesia, dystonia, and rigidity than with the choreic movements characteristic of the adultonset disorder. The disease is gradually progressive, with median survival approximately

15 years after motor symptom diagnosis.

Phenotypic expression of Huntington's disease varies by presence of motor, cognitive,

and psychiatric symptoms. Psychiatric and cognitive abnormalities can predate the motor

abnormality by at least 15 years. Initial symptoms requiring care often include irritabity,

anxiety, or depressed mood. Other behavioral disturbances may include pronounced apathy, disinhibition, impulsivity, and impaired insight, with apathy often becoming more

progressive over time. Early movement symptoms may involve the appearance of fidgetiness of the extremities as well as mild apraxia (i.e., difficulty with purposeful movements),

particularly with fine motor tasks. As the disorder progresses, other motor problems include impaired gait (ataxia) and postural instability. Motor impairment eventually affects

speech production (dysarthria) such that the speech becomes very difficult to understand.

which may result in significant distress resulting from the communication barrier in the

context of comparatively intact cognition. Advanced motor disease severely affects gait

with progressive ataxia. Eventually individuals become nonambulatory. End-stage motor

disease impairs motor control of eating and swallowing, typically a major contributor to

the death of the individual from aspiration pneumonia.

Risk and Prognostic Factors

Genetic and physiological. The genetic basis of Huntington's disease is a fully penetrant

autosomal dominant expansion of the CAG trincleotide, often called a CAG repeat in the

huntingtin gene. A repeat length of 36 or more is invariably associated with Huntington's

disease, with longer repeat lengths associated with early age at onset. A CAG repeat length

of 36 or more is invariably associated with Huntington's disease.

Diagnostic iVlaricers

Genetic testing is the primary laboratory test for the determination of Huntington's disease, which is an autosomal dominant disorder with complete penetrance. The trinucleotide CAG is observed to have a repeat expansion in the gene that encodes huntingtin

protein on chromosome 4. A diagnosis of Huntington's disease is not made in the presence

of the gene expansion alone, but the diagnosis is made only after symptoms become manifest. Some individuals with a positive family history request genetic testing in a presymptomatic stage. Associated features may also include neuroimaging changes; volume loss in

the basal ganglia, particularly the caudate nucleus and putamen, is well known to occur

and progresses over the course of illness. Other structural and functional changes have

been observed in brain imaging but remain research measures.

Functionai Consequences of iViajor or IVliid

Neurocognitive Disorder Due to Huntington’s Disease

In the prodromal phase of illness and at early diagnosis, occupational decline is most common, with most individuals reporting some loss of ability to engage in their typical work.

The emotional, behavioral, and cognitive aspects of Huntington's disease, such as disinhibition and personality changes, are highly associated with functional decline. Cognitive

deficits that contribute most to functional decline may include speed of processing, initiation, and attention rather than memory impairment. Given that Huntington's disease onset occurs in productive years of life, it may have a very disruptive effect on performance

in the work setting as well as social and family life. As the disease progresses, disability

from problems such as impaired gait, dysarthria, and impulsive or irritable behaviors may

substantially add to the level of impairment and daily care needs, over and above the care

needs attributable to the cognitive decline. Severe choreic movements may substantially

interfere with provision of care such as bathing, dressing, and toileting.

Differential Diagnosis

Other mental disorders. Early symptoms of Huntington's disease may include instability of mood, irritability, or compulsive behaviors that may suggest another mental disorder. However, genetic testing or the development of motor symptoms will distinguish the

presence of Huntington's disease.

Other neurocognitive disorders. The early symptoms of Huntington's disease, particularly symptoms of executive dysfunction and impaired psychomotor speed, may resemble

other neurocognitive disorders (NCDs), such as major or mild vascular NCD.

Other movement disorders. Huntington's disease must also be differentiated from other

disorders or conditions associated with chorea, such as Wilson's disease, drug-induced

tardive dyskinesia, Sydenham's chorea, systemic lupus erythematosus, or senile chorea.

Rarely, individuals may present with a course similar to that of Huntington's disease but

without positive genetic testing; this is considered to be a Huntington's disease phenocopy that results from a variety of potential genetic factors.

Major or Mild Neurocognitive Disorder

Due to Another Medical Condition

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. There is evidence from the history, physical examination, or laboratory findings that the

neurocognitive disorder is the pathophysiological consequence of another medical

condition.

C. The cognitive deficits are not better explained by another mental disorder or another

specific neurocognitive disorder (e.g., Alzheimer’s disease, HIV infection).

Coding note: For major neurocognitive disorder due to another medical condition, with

behavioral disturbance, code first the other medical condition, followed by the major neurocognitive disorder due to another medical condition, with behavioral disturbance (e.g.,

340 [G35] multiple sclerosis, 294.11 [F02.81] major neurocognitive disorder due to multiple sclerosis, with behavioral disturbance). For major neurocognitive disorder due to another medical condition, without behavioral disturbance, code first the other medical

condition, followed by the major neurocognitive disorder due to another medical condition,

without behavioral disturbance (e.g., 340 [G35] multiple sclerosis, 294.10 [F02.80] major

neurocognitive disorder due to multiple sclerosis, without behavioral disturbance).

For mild neürocognitive disorder due to another medical condition, code 331.83 (G31.84).

(Note: Do not use the additional code for the other medical condition. Behavioral disturbance cannot be coded but should still be indicated in writing.)

Diagnostic Features

A number of other medical conditions can cause neurocognitive disorders (NCDs). These

conditions include structural lesions (e.g., primary or secondary brain tumors, subdural

hematoma, slowly progressive or normal-pressure hydrocephalus), hypoxia related to hypoperfusion from heart failure, endocrine conditions (e.g., hypothyroidism, hypercalcemia, hypoglycemia), nutritional conditions (e.g., deficiencies of thiamine or niacin), other

infectious conditions (e.g., neurosyphilis, cryptococcosis), immune disorders (e.g., temporal arteritis, systemic lupus erythematosus), hepatic or renal failure, metabolic conditions

(e.g., Kufs' disease, adrenoleukodystrophy, metachromatic leukodystrophy, other storage

diseases of adulthood and childhood), and other neurological conditions (e.g., epilepsy,

multiple sclerosis). Unusual causes of central nervous system injury, such as electrical

shock or intracranial radiation, are generally evident from the history. The temporal association between the onset or exacerbation of the medical condition and the development of

the cognitive deficit offers the greatest support that the NCD is induced by the medical

condition. Diagnostic certainty regarding this relationship may be increased if the neurocognitive deficits ameliorate partially or stabilize in the context of treatment of the medical

condition.

Development and Course

Typically the course of the NCD progresses in a manner that is commensurate with progression of the underlying medical disorder. In circumstances where the medical disorder is treatable (e.g., hypothyroidism), the neurocognitive deficit may improve or at least not progress.

When the medical condition has a deteriorative course (e.g., secondary progressive multiple

sclerosis), the neurocognitive deficits will progress along with the temporal course of illness.

Diagnostic iVlarlcers

Associated physical examination and laboratory findings and other clinical features depend on the nature and severity of the medical condition.

Differential Diagnosis

Other major or mild neurocognitive disorder. The presence of an attributable medical

condition does not entirely exclude the possibility of another major or mild NCD. If cognitive deficits persist following successful treatment of an associated medical condition,

then another etiology may be responsible for the cognitive decline.

Major or Mild Neurocognitive Disorder

Due to Multiple Etiologies

Diagnostic Criteria

A. The criteria are met for major or mild neurocognitive disorder.

B. There is evidence from the history, physical examination, or laboratory findings that the

neurocognitive disorder is the pathophysiological consequence of more than one etiological process, excluding substances (e.g., neurocognitive disorder due to Alzheimer’s disease with subsequent development of vascular neurocognitive disorder).

Note: Please refer to the diagnostic criteria for the various neurocognitive disorders due

to specific medical conditions for guidance on establishing the particular etiologies.

C. The cognitive deficits are not better explained by another mental disorder and do not

occur exclusively during the course of a delirium.

Coding note: For major neurocognitive disorder due to multiple etiologies, with behavioral

disturbance, code 294.11 (F02.81); for major neurocognitive disorder due to multiple etiologies, without behavioral disturbance, code 294.10 (F02.80). All of the etiological medical

conditions (with the exception of vascular disease) should be coded and listed separately

immediately before major neurocognitive disorder due to multiple etiologies (e.g., 331.0

[G30.9] Alzheimer’s disease; 331.82 [G31.83] Lewy body disease; 294.11 [F02.81] major

neurocognitive disorder due to multiple etiologies, with behavioral disturbance).

When a cerebrovascular etiology is contributing to the neurocognitive disorder, the diagnosis of vascular neurocognitive disorder should be listed in addition to major neurocognitive

disorder due to multiple etiologies. For example, for a presentation of major neurocognitive

disorder due to both Alzheimer’s disease and vascular disease, with behavioral disturbance,

code the following: 331.0 (G30.9) Alzheimer’s disease; 294.11 (F02.81) major neurocognitive disorder due to multiple etiologies, with behavioral disturbance; 290.40 (FOI .51) major

vascular neurocognitive disorder, with behavioral disturbance.

For mild neurocognitive disorder due to multiple etiologies, code 331.83 (G31.84). (Note:

Do not use the additional codes for the etiologies. Behavioral disturbance cannot be coded

but should still be indicated in writing.)

This category is included to cover the clinical presentation of a neurocognitive disorder (NCD)

for v^hich there is^^evidence that multiple medical conditions have played a probable role in the

development of the NCD. In addition to evidence indicative of the presence of multiple medical conditions that are known to cause NCD (i.e., findings from the history and physical examination, and laboratory findings), it may be helpful to refer to the diagnostic criteria and text

for the various medical etiologies (e.g., NCD due to Parkinson's disease) for more information

on establishing the etiological connection for that particular medical condition.

Unspecified Neurocognitive Disorder

799.59 (R41.9)

This category applies to presentations in which symptoms characteristic of a neurocognitive disorder that cause clinically significant distress or impairment in social, occupational,

or other important areas of functioning predominate but do not meet the full criteria for any

of the disorders in the neurocognitive disorders diagnostic class. The unspecified neurocognitive disorder category is used in situations in which the precise etiology cannot be

determined with sufficient certainty to make an etiological attribution.

Coding note: For unspecified major or mild neurocognitive disorder, code 799.59 (R41.9).

(Note: Do not use additional codes for any presumed etiological medical conditions. Behavioral disturbance cannot be coded but may be indicated in writing.)

Personality

Disordet#

T h is C h s p te r b eg in s with a general definition of personaliiy disorder that applies

to each of the 10 specific personality disorders. A personality disorder is an enduring pattern

of inner experience and behavior that deviates markedly from the expectations of the individual's culture, is pervasive and inflexible, has an onset in adolescence or early adulthood, is stable over time, and leads to distress or impairment.

With any ongoing review process, especially one of this complexity, different viewpoints emerge, and an effort was made to accommodate them. Thus, personality disorders

are included in both Sections II and III. The material in Section II represents an update of

text associated with the same criteria found in DSM-IV-TR, whereas Section III includes

the proposed research model for personality disorder diagnosis and conceptualization developed by the DSM-5 Personality and Personality Disorders Work Group. As this field

evolves, it is hoped that both versions will serve clinical practice and research initiatives,

respectively.

The following personality disorders are included in this chapter.

• Paranoid personality disorder is a pattern of distrust and suspiciousness such that others' motives are interpreted as malevolent.

• Schizoid personality disorder is a pattern of detachment from social relationships and

a restricted range of emotional expression.

• Schizotypal personality disorder is a pattern of acute discomfort in close relationships,

cognitive or perceptual distortions, and eccentricities of behavior.

• Antisocial personality disorder is a pattern of disregard for, and violation of, the rights

of others.

• Borderline personality disorder is a pattern of instability in interpersonal relationships, self-image, and affects, and marked impulsivity.

• Histrionic personality disorder is a pattern of excessive emotionality and attention

seeking.

• Narcissistic personality disorder is a pattern of grandiosity, need for admiration, and

lack of empathy.

• Avoidant personality disorder is a pattern of social inhibition, feelings of inadequacy,

and hypersensitivity to negative evaluation.

• Dependent personality disorder is a pattern of submissive and clinging behavior related to an excessive need to be taken care of.

• Obsessive-compulsive personality disorder is a pattern of preoccupation with orderliness, perfectionism, and control.

• Personality change due to another medical condition is a persistent personality disturbance that is judged to be due to the direct physiological effects of a medical condition (e.g., frontal lobe lesion).

• Other specified personality disorder and unspecified personality disorder is a category provided for two situations: 1) the individual's personality pattern meets the general criteria for a personality disorder, and traits of several different personality

disorders are present, but the criteria for any specific personality disorder are not met;

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