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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