Diagnostic_and_Statistical 02

 disorder is not a distinct nosological category. Thus, dimensional assessments of depression and mania for all psychotic disorders alert clinicians to mood pathology and the need

to treat where appropriate. The Section III scale also includes a dimensional assessment of

cognitive impairment. Many individuals with psychotic disorders have impairments in a

range of cognitive domains that predict functional status. Clinical neuropsychological assessment can help guide diagnosis and treatment, but brief assessments without formal

neuropsychological assessment can provide useful information that can be sufficient for

diagnostic purposes. Formal neuropsychological testing, when conducted, should be administered and scored by personnel trained in the use of testing instruments. If a formal

neuropsychological assessment is not conducted, the clinician should use the best available information to make a judgment. Further research on these assessments is necessary

in order to determine their clinical utility; thus, the assessments available in Section III

should serve as a prototype to stimulate such research.

Schizotypal (Personality) Disorder

Criteria and text for schizotypal personality disorder can be found in the chapter "Personality Disorders." Because this disorder is considered part of the schizophrenia spectrum of

disorders, and is labeled in this section of ICD-9 and ICD-10 as schizotypal disorder, it is

listed in this chapter and discussed in detail in the DSM-5 chapter "Personality Disorders."

Delusional Disorder

Diagnostic Criteria 297.1 (F22)

A. The presence of one (or more) delusions with a duration of 1 month or longer.

B. Criterion A for schizophrenia has never been met.

Note: Hallucinations, if present, are not prominent and are related to the delusional

theme (e.g., the sensation of being infested with insects associated with delusions of

infestation).

C. Apart from the impact of the delusion(s) or its ramifications, functioning is not markedly

impaired, and behavior is not obviously bizarre or odd.

D. If manic or major depressive episodes have occurred, these have been brief relative

to the duration of the delusional periods.

E. The disturbance is not attributable to the physiological effects of a substance or another medical condition and is not better explained by another mental disorder, such

as body dysmorphic disorder or obsessive-compulsive disorder.

Specify whether:

Erotomanie type: This subtype applies when the central theme of the delusion is that

another person is in love with the individual.

Grandiose type: This subtype applies when the central theme of the delusion is the

conviction of having some great (but unrecognized) talent or insight or having made

some important discovery.

Jeaious type: This subtype applies when the central theme of the individual’s delusion

is that his or her spouse or lover is unfaithful.

Persecutory type: This subtype applies when the central theme of the delusion involves the individual’s belief that he or she is being conspired against, cheated, spied

on, followed, poisoned or drugged, maliciously maligned, harassed, or obstructed in

the pursuit of long-term goals.

Somatic type: This subtype applies when the central theme of the delusion involves

bodily functions or sensations.

Mixed type: This subtype applies when no one delusional theme predominates.

Unspecified type: This subtype applies when the dominant delusional belief cannot

be clearly determined or is not described in the specific types (e.g., referential delusions without a prominent persecutory or grandiose component).

Specify if:

With bizarre content: Delusions are deemed bizarre if they are clearly implausible, not

understandable, and not derived from ordinary life experiences (e.g., an individual’s belief that a stranger has removed his or her internal organs and replaced them with someone else’s organs without leaving any wounds or scars).

Specify if:

The following course specifiers are only to be used after a 1 -year duration of the disorder:

First episode, currently in acute episode: First manifestation of the disorder meeting the defining diagnostic symptom and time criteria. An acute episode is a time period in which the symptom criteria are fulfilled.

First episode, currently in partial remission: Partial remission is a time period during which an improvement after a previous episode is maintained and in which the defining criteria of the disorder are only partially fulfilled.

First episode, currently in full remission: Full remission is a period of time after a

previous episode during which no disorder-specific symptoms are present.

lUlultiple episodes, currently in acute episode

Multiple episodes, currently in partial remission

Multiple episodes, currently in full remission

Continuous: Symptoms fulfilling the diagnostic symptom criteria of the disorder are

remaining for the majority of the illness course, with subthreshold symptom periods being very brief relative to the overall course.

Unspecified

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, and negative symptoms. Each of these symptoms may be rated for its current

severity (most severe in the last 7 days) on a 5-point scale ranging from 0 (not present)

to 4 (present and severe). (See Clinician-Rated Dimensions of Psychosis Symptom

Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of delusional disorder can be made without using this severity specifier.

Subtypes

In érotomanie type, the central theme of the delusion is that another person is in love with

the individual. The person about whom this conviction is held is usually of higher status

(e.g., a famous individual or a superior at work) but can be a complete stranger. Efforts to

contact the object of the delusion are common. In grandiose type, the central theme of the delusion is the conviction of having some great talent or insight or of having made some important discovery. Less commonly, the individual may have the delusion of having a

special relationship with a prominent individual or of being a prominent person (in which

case the actual individual may be regarded as an impostor). Grandiose delusions may

have a religious content. In jealous type, the central theme of the delusion is that of an unfaithful partner. This belief is arrived at without due cause and is based on incorrect inferences supported by small bits of "evidence" (e.g., disarrayed clothing). The individual

with the delusion usually confronts the spouse or lover and attempts to intervene in the

imagined infidelity. In persecutory type, the central theme of the delusion involves the in­

dividual's belief of being conspired against, cheated, spied on, followed, poisoned, maliciously maligned, harassed, or obstructed in the pursuit of long-term goals. Small slights

may be exaggerated and become the focus of a delusional system. The affected individual

may engage in repeated attempts to obtain satisfaction by legal or legislative action. Individuals with persecutory delusions are often resentful and angry and may resort to violence against those they believe are hurting them. In somatic type, the central theme of the

delusion involves bodily functions or sensations. Somatic delusions can occur in several

forms. Most common is the belief that the individual emits a foul odor; that there is an infestation of insects on or in the skin; that there is an internal parasite; that certain parts of

the body are misshapen or ugly; or that parts of the body are not functioning.

Diagnostic Features

The essential feature of delusional disorder is the presence of one or more delusions that

persist for at least 1 month (Criterion A). A diagnosis of delusional disorder is not given if

the individual has ever had a symptom presentation that met Criterion A for schizophrenia (Criterion B). Apart from the direct impact of the delusions, impairments in psychosocial functioning may be more circumscribed than those seen in other psychotic disorders

such as schizophrenia, and behavior is not obviously bizarre or odd (Criterion C). If mood

episodes occur concurrently with the delusions, the total duration of these mood episodes

is brief relative to the total duration of the delusional periods (Criterion D). The delusions

are not attributable to the physiological effects of a substance (e.g., cocaine) or another

medical condition (e.g., Alzheimer's disease) and are not better explained by another mental disorder, such as body dysmorphic disorder or obsessive-compulsive disorder (Criterion E).

In addition to the five symptom domain areas identified in the diagnostic criteria, the

assessment of cognition, depression, and mania symptom domains is vital for making critically important distinctions between the various schizophrenia spectrum and other psychotic disorders.

Associated Features Supporting Diagnosis

Social, marital, or work problems can result from the delusional beliefs of delusional disorder. Individuals with delusional disorder may be able to factually describe that others

view their beliefs as irrational but are unable to accept this themselves (i.e., there may be

"factual insight" but no true insight). Many individuals develop irritable or dysphoric

mood, which can usually be understood as a reaction to their delusional beliefs. Anger and

violent behavior can occur with persecutory, jealous, and érotomanie types. The individual may engage in htigious or antagonistic behavior (e.g., sending hundreds of letters of

protest to the government). Legal difficulties can occur, particularly in jealous and érotomanie types.

Prevaience

The lifetime prevalence of delusional disorder has been estimated at around 0.2%, and the

most frequent subtype is persecutory. Delusional disorder, jealous type, is probably more

common in males than in females, but there are no major gender differences in the overall

frequency of delusional disorder.

Deveiopment and Course

On average, global function is generally better than that observed in schizophrenia. Although the diagnosis is generally stable, a proportion of individuals go on to develop

schizophrenia. Delusional disorder has a significant familial relationship with both

schizophrenia and schizotypal personality disorder. Although it can occur in younger age

groups, the condition may be more prevalent in older individuals.

Culture-Related Diagnostic Issues

An individual's cultural and religious background must be taken into account in evaluating the possible presence of delusional disorder. The content of delusions also varies

across cultural contexts.

Functional Consequences of Delusional Disorder

The functional impairment is usually more circumscribed than that seen with other psychotic disorders, although in some cases, the impairment may be substantial and include

poor occupational functioning and social isolation. When poor psychosocial functioning is

present, delusional beliefs themselves often play a significant role. A common characteristic of individuals with delusional disorder is the apparent normality of their behavior

and appearance when their delusional ideas are not being discussed or acted on.

Differential Diagnosis

Obsessive-compulsive and related disorders. If an individual with obsessive-compulsive disorder is completely convinced that his or her obsessive-compulsive disorder beliefs

are true, then the diagnosis of obsessive-compulsive disorder, with absent insight/delusional beliefs specifier, should be given rather than a diagnosis of delusional disorder.

Similarly, if an individual with body dysmorphic disorder is completely convinced that

his or her body dysmorphic disorder beliefs are true, then the diagnosis of body dysmorphic disorder, with absent insight/delusional beliefs specifier, should be given rather than

a diagnosis of delusional disorder.

Delirium, major neurocognitive disorder, psychotic disorder due to another medical condition, and substance/medication-induced psychotic disorder. Individuals with these

disorders may present with symptoms that suggest delusional disorder. For example, simple persecutory delusions in the context of major neurocognitive disorder would be diagnosed as major neurocognitive disorder, with behavioral disturbance. A substance/

medication-induced psychotic disorder cross-sectionally may be identical in symptomatology to delusional disorder but can be distinguished by the chronological relationship

of substance use to the onset and remission of the delusional beliefs.

Schizophrenia and schizophreniform disorder. Delusional disorder can be distinguished

from schizophrenia and schizophreniform disorder by the absence of the other characteristic symptoms of the active phase of schizophrenia.

Depressive and bipolar disorders and schizoaffective disorder. These disorders may

be distinguished from delusional disorder by the temporal relationship between the mood

disturbance and the delusions and by the severity of the mood symptoms. If delusions occur exclusively during mood episodes, the diagnosis is depressive or bipolar disorder with

psychotic features. Mood symptoms that meet full criteria for a mood episode can be superimposed on delusional disorder. Delusional disorder can be diagnosed only if the total

duration of all mood episodes remains brief relative to the total duration of the delusional

disturbance. If not, then a diagnosis of other specified or unspecified schizophrenia spectrum and other psychotic disorder accompanied by other specified depressive disorder,

unspecified depressive disorder, other specified bipolar and related disorder, or unspecified bipolar and related disorder is appropriate.

Brief Psychotic Disorder

Diagnostic Criteria 298.8 (F23)

A. Presence of one (or more) of the following symptoms. At least one of these must be

(1), (2), or (3):

1. Delusions.

2. Hallucinations.

3. Disorganized speech (e.g., frequent derailment or incoherence).

4. Grossly disorganized or catatonic behavior.

Note: Do not include a symptom if it is a culturally sanctioned response.

B. Duration of an episode of the disturbance is at least 1 day but less than 1 month, with

eventual full return to premorbid level of functioning.

C. The disturbance is not better explained by major depressive or bipolar disorder with

psychotic features or another psychotic disorder such as schizophrenia or catatonia,

and is not attributable to the physiological effects of a substance (e.g., a drug of abuse,

a medication) or another medical condition.

Specify if:

With marked stressor(s) (brief reactive psychosis): If symptoms occur in response to

events that, singly or together, would be markedly stressful to almost anyone in similar

circumstances in the individual’s culture.

Without marited stressor(s): If symptoms do not occur in response to events that,

singly or together, would be markedly stressful to almost anyone in similar circumstances in the individual’s culture.

With postpartum onset: If onset is during pregnancy or within 4 weeks postpartum.

Specify if:

With catatonia (refer to the criteria for catatonia associated with another mental disorder, pp. 119-120, for definition)

Coding note: Use additional code 293.89 (F06.1) catatonia associated with brief

psychotic disorder to indicate the presence of the comorbid catatonia.

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, and negative symptoms. Each of these symptoms may be rated for its current

severity (most severe in the last 7 days) on a 5-point scale ranging from 0 (not present)

to 4 (present and severe). (See Clinician-Rated Dimensions of Psychosis Symptom

Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of brief psychotic disorder can be made without using this severity

specifier._____________________________________________________________

Diagnostic Features

The essential feature of brief psychotic disorder is a disturbance that involves the sudden

onset of at least one of the following positive psychotic symptoms: delusions, hallucinations, disorganized speech (e.g., frequent derailment or incoherence), or grossly abnormal

psychomotor behavior, including catatonia (Criterion A). Sudden onset is defined as

change from a nonpsychotic state to a clearly psychotic state within 2 weeks, usually without a prodrome. An episode of the disturbance lasts at least 1 day but less than 1 month,

and the individual eventually has a full return to the premorbid level of functioning (Cri­

terion B). The disturbance is not better explained by a depressive or bipolar disorder with

psychotic features, by schizoaffective disorder, or by schizophrenia and is not attributable

to the physiological effects of a substance (e.g., a hallucinogen) or another medical condition (e.g., subdural hematoma) (Criterion C).

In addition to the five symptom domain areas identified in the diagnostic criteria, the

assessment of cognition, depression, and mania symptom domains is vital for making critically important distinctions between the various schizophrenia spectrum and other psychotic disorders.

Associated Features Supporting Diagnosis

Individuals with brief psychotic disorder typically experience emotional turmoil or overwhelming confusion. They may have rapid shifts from one intense affect to another.

Although the disturbance is brief, the level of impairment may be severe, and supervision

may be required to ensure that nutritional and hygienic needs are met and that the individual is protected from the consequences of poor judgment, cognitive impairment, or acting on the basis of delusions. There appears to be an increased risk of suicidal behavior,

particularly during the acute episode.

Prevaience

In the United States, brief psychotic disorder may account for 9% of cases of first-onset

psychosis. Psychotic disturbances that meet Criteria A and C, but not Criterion B, for brief

psychotic disorder (i.e., duration of active symptoms is 1-6 months as opposed to remission within 1 month) are more common in developing countries than in developed countries. Brief psychotic disorder is twofold more common in females than in males.

Deveiopment and Course

Brief psychotic disorder may appear in adolescence or early adulthood, and onset can occur across the lifespan, with the average age at onset being the mid 30s. By definition, a

diagnosis of brief psychotic disorder requires a full remission of all symptoms and an

eventual full return to the premorbid level of functioning within 1 month of the onset of the

disturbance. In some individuals, the duration of psychotic symptoms may be quite brief

(e.g., a few days).

Risic and Prognostic Factors

Temperamental. Preexisting personality disorders and traits (e.g., schizotypal personality disorder; borderline personality disorder; or traits in the psychoticism domain, such

as perceptual dysregulation, and the negative affectivity domain, such as suspiciousness)

may predispose the individual to the development of the disorder.

Cuiture-Reiated Diagnostic issues

It is important to distinguish symptoms of brief psychotic disorder from culturally sanctioned response patterns. For example, in some religious ceremonies, an individual may

report hearing voices, but these do not generally persist and are not perceived as abnormal

by most members of the individual's community. In addition, cultural and religious background must be taken into account when considering whether beliefs are delusional.

Functionai Consequences of Brief Psycliotic Disorder

Despite high rates of relapse, for most individuals, outcome is excellent in terms of social

functioning and symptomatology.

Differential Diagnosis

Other medical conditions. A variety of medical disorders can manifest with psychotic

symptoms of short duration. Psychotic disorder due to another medical condition or a delirium is diagnosed when there is evidence from the history, physical examination, or laboratory tests that the delusions or hallucinations are the direct physiological consequence

of a specific medical condition (e.g., Cushing's syndrome, brain tumor) (see 'Tsychotic

Disorder Due to Another Medical Condition" later in this chapter).

Substance-related disorders. Substance/medication-induced psychotic disorder, substance-induced delirium, and substance intoxication are distinguished from brief psychotic

disorder by the fact that a substance (e.g., a drug of abuse, a medication, exposure to a toxin)

is judged to be etiologically related to the psychotic symptoms (see ''Substance/MedicationInduced Psychotic Disorder" later in this chapter). Laboratory tests, such as a urine drug

screen or a blood alcohol level, may be helpful in making this determination, as may a careful history of substance use with attention to temporal relationships between substance intake and onset of the symptoms and to the nature of the substance being used.

Depressive and bipolar disorders. The diagnosis of brief psychotic disorder cannot be

made if the psychotic symptoms are better explained by a mood episode (i.e., the psychotic

symptoms occur exclusively during a full major depressive, manic, or mixed episode).

Other psychotic disorders. If the psychotic symptoms persist for 1 month or longer, the

diagnosis is either schizophreniform disorder, delusional disorder, depressive disorder

with psychotic features, bipolar disorder with psychotic features, or other specified or unspecified schizophrenia spectrum and other psychotic disorder, depending on the other

symptoms in the presentation. The differential diagnosis between brief psychotic disorder

and schizophreniform disorder is difficult when the psychotic symptoms have remitted before 1 month in response to successful treatment with medication. Careful attention should

be given to the possibility that a recurrent disorder (e.g., bipolar disorder, recurrent acute exacerbations of schizophrenia) may be responsible for any recurring psychotic episodes.

Malingering and factitious disorders. An episode of factitious disorder, with predominantly psychological signs and symptoms, may have the appearance of brief psychotic

disorder, but in such cases there is evidence that the symptoms are intentionally produced.

When malingering involves apparently psychotic symptoms, there is usually evidence

that the illness is being feigned for an understandable goal.

Personality disorders. In certain individuals with personality disorders, psychosocial

stressors may precipitate brief periods of psychotic symptoms. These symptoms are usually transient and do not warrant a separate diagnosis. If psychotic symptoms persist for at

least 1 day, an additional diagnosis of brief psychotic disorder may be appropriate.

Schizophreniform Disorder

Diagnostic Criteria 295.40 (F20.81)

A. Two (or more) of the following, each present for a significant portion of time during a

1-month period (or less if successfully treated). At least one of these must be (1), (2),

or (3):

1. Delusions.

2. Hallucinations.

3. Disorganized speech (e.g., frequent derailment or incoherence).

4. Grossly disorganized or catatonic behavior.

5. Negative symptoms (i.e., diminished emotional expression or avolition).

B. An episode of the disorder lasts at least 1 month but less than 6 months. When the

diagnosis must be made without waiting for recovery, it should be qualified as “provisional.” '

C. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have

been ruled out because either 1 ) no major depressive or manic episodes have occurred

concurrently with the active-phase symptoms, or 2) if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration

of the active and residual periods of the illness.

D. The disturbance is not attributable to the physiological effects of a substance (e.g., a

drug of abuse, a medication) or another medical condition.

Specify if:

With good prognostic features: This specifier requires the presence of at least two

of the following features: onset of prominent psychotic symptoms within 4 weeks of the

first noticeable change in usual behavior or functioning; confusion or perplexity: good

premorbid social and occupational functioning; and absence of blunted or flat affect.

Without good prognostic features: This specifier is applied if two or more of the

above features have not been present.

Specify if:

With catatonia (refer to the criteria for catatonia associated with another mental disorder, pp. 119-120, for definition).

Coding note: Use additional code 293.89 (F06.1) catatonia associated with schizophreniform disorder to indicate the presence of the comorbid catatonia.

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, and negative symptoms. Each of these symptoms may be rated for its current

severity (most severe in the last 7 days) on a 5-point scale ranging from 0 (not present)

to 4 (present and severe). (See Clinician-Rated Dimensions of Psychosis Symptom

Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of schizophreniform disorder can be made without using this severity

specifier.

Note: For additional information on Associated Features Supporting Diagnosis, Development and Course (age-related factors), Culture-Related Diagnostic Issues, Gender-Related

Diagnostic Issues, Differential Diagnosis, and Comorbidity, see the corresponding sections in schizophrenia.

Diagnostic Features

The characteristic symptoms of schizophreniform disorder are identical to those of schizophrenia (Criterion A). Schizophreniform disorder is distinguished by its difference in duration: the total duration of the illness, including prodromal, active, and residual phases, is

at least 1 month but less than 6 months (Criterion B). The duration requirement for schizophreniform disorder is intermediate between that for brief psychotic disorder, which lasts

more than 1 day and remits by 1 month, and schizophrenia, which lasts for at least 6 months.

The diagnosis of schizophreniform disorder is made under two conditions. 1) when an episode of illness lasts between 1 and 6 months and the individual has already recovered,

and 2) when an individual is symptomatic for less than the 6 months' duration required for

the diagnosis of schizophrenia but has not yet recovered. In this case, the diagnosis should

be noted as "schizophreniform disorder (provisional)" because it is uncertain if the individual will recover from the disturbance within the 6-month period. If the disturbance persists beyond 6 months, the diagnosis should be changed to schizophrenia.

Another distinguishing feature of schizophreniform disorder is the lack of a criterion

requiring impaired social and occupational functioning. While such impairments may potentially be present, they are not necessary for a diagnosis of schizophreniform disorder.

In addition to the five symptom domain areas identified in the diagnostic criteria, the

assessment of cognition, depression, and mania symptom domains is vital for making critically important distinctions between the various schizophrenia spectrum and other psychotic disorders.

Associated Features Supporting Diagnosis

As with schizophrenia, currently there are no laboratory or psychometric tests for schizophreniform disorder. There are multiple brain regions where neuroimaging, neuropathological, and neurophysiological research has indicated abnormalities, but none are

diagnostic.

Prevaience

Incidence of schizophreniform disorder across sociocultural settings is likely similar to

that observed in schizophrenia. In the United States and other developed countries, the incidence is low, possibly fivefold less than that of schizophrenia. In developing countries,

the incidence may be higher, especially for the specifier ''with good prognostic features";

in some of these settings schizophreniform disorder may be as common as schizophrenia.

Deveiopment and Course

The development of schizophreniform disorder is similar to that of schizophrenia. About

one-third of individuals with an initial diagnosis of schizophreniform disorder (provisional) recover within the 6-month period and schizophreniform disorder is their final diagnosis. The majority of the remaining two-thirds of individuals will eventually receive a

diagnosis of schizophrenia or schizoaffective disorder.

Risic and Prognostic Factors

Genetic and physiological. Relatives of individuals with schizophreniform disorder

have an increased risk for schizophrenia.

Functionai Consequences of

Sciiizophreniform Disorder

For the majority of individuals with schizophreniform disorder who eventually receive a

diagnosis of schizophrenia or schizoaffective disorder, the functional consequences are

similar to the consequences of those disorders. Most individuals experience dysfunction in

several areas of daily functioning, such as school or work, interpersonal relationships, and

self-care. Individuals who recover from schizophreniform disorder have better functional

outcomes.

Differentiai Diagnosis

Other mental disorders and medical conditions. A wide variety of mental and medical

conditions can manifest with psychotic symptoms that must be considered in the differential diagnosis of schizophreniform disorder. These include psychotic disorder due to

another medical condition or its treatment; delirium or major neurocognitive disorder;

substance/medication-induced psychotic disorder or delirium; depressive or bipolar

disorder with psychotic features; schizoaffective disorder; other specified or unspecified bipolar and related disorder; depressive or bipolar disorder with catatonic features; schizophre-

nia; brief psychotic disorder; delusional disorder; other specified or unspecified schizophrenia spectrum and other psychotic disorder; schizotypal, schizoid, or paranoid

personality disorders; autism spectrum disorder; disorders presenting in childhood with

disorganized speech; attention-deficit/hyperactivity disorder; obsessive-compulsive disorder; posttraumatic stress disorder; and traumatic brain injury.

Since the diagnostic criteria for schizophreniform disorder and schizophrenia differ

primarily in duration of illness, the discussion of the differential diagnosis of schizophrenia also applies to schizophreniform disorder.

Brief psychotic disorder. Schizophreniform disorder differs in duration from brief psychotic disorder, which has a duration of less than 1 month.

Schizophrenia

Diagnostic Criteria 295.90 (F20.9)

A. Two (or more) of the following, each present for a significant portion of time during a

1 -month period (or less if successfully treated). At least one of these must be (1 ), (2), or (3):

1. Delusions.

2. Hallucinations.

3. Disorganized speech (e.g., frequent derailment or incoherence).

4. Grossly disorganized or catatonic behavior.

5. Negative symptoms (i.e., diminished emotional expression or avolition).

B. For a significant portion of the time since the onset of the disturbance, level of functioning in one or more major areas, such as work, interpersonal relations, or self-care, is

markedly below the level achieved prior to the onset (or when the onset is in childhood

or adolescence, there is failure to achieve expected level of interpersonal, academic,

or occupational functioning).

C. Continuous signs of the disturbance persist for at least 6 months. This 6-month period

must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual

symptoms. During these prodromal or residual periods, the signs of the disturbance may

be manifested by only negative symptoms or by two or more symptoms listed in Criterion

A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).

D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features

have been ruled out because either 1 ) no major depressive or manic episodes have

occurred concurrently with the active-phase symptoms, or 2) if mood episodes have

occurred during active-phase symptoms, they have been present for a minority of the

total duration of the active and residual periods of the illness.

E. The disturbance is not attributable to the physiological effects of a substance (e.g., a

drug of abuse, a medication) or another medical condition.

F. If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia,

are also present for at least 1 month (or less if successfully treated).

Specify if:

The following course specifiers are only to be used after a 1-year duration of the disorder

and if they are not in contradiction to the diagnostic course criteria.

First episode, currently in acute episode: First manifestation of the disorder meeting the defining diagnostic symptom and time criteria. An acute episode is a time period in which the symptom criteria are fulfilled.

First episode, currently in partial remission: Partial remission is a period of time

during which an improvement after a previous episode is maintained and in which the

defining criteria of the disorder are only partially fulfilled.

First episode, currently in full remission: Full remission is a period of time after a

previous episode during which no disorder-specific symptoms are present.

Multiple episodes, currently in acute episode: Multiple episodes may be determined after a minimum of two episodes (i.e., after a first episode, a remission and a

minimum of one relapse).

■Multiple episodes, currently in partial remission

Multiple episodes, currently in full remission

Continuous: Symptoms fulfilling the diagnostic symptom criteria of the disorder are

remaining for the majority of the illness course, with subthreshold symptom periods being very brief relative to the overall course.

Unspecified

Specify if:

With catatonia (refer to the criteria for catatonia associated with another mental disorder,

pp. 119-120, for definition).

Coding note: Use additional code 293.89 (F06.1) catatonia associated with

schizophrenia to indicate the presence of the comorbid catatonia.

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, and negative symptoms. Each of these symptoms may be rated for its current

severity (most severe in the last 7 days) on a 5-point scale ranging from 0 (not present)

to 4 (present and severe). (See Clinician-Rated Dimensions of Psychosis Symptom

Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of schizophrenia can be made without using this severity specifier.

Diagnostic Features

The characteristic symptoms of schizophrenia involve a range of cognitive, behavioral, and

emotional dysfunctions, but no single symptom is pathognomonic of the disorder. The diagnosis involves the recognition of a constellation of signs and symptoms associated with

impaired occupational or social functioning. Individuals with the disorder will vary substantially on most features, as schizophrenia is a heterogeneous clinical syndrome.

At least two Criterion A symptoms must be present for a significant portion of time

during a 1-month period or longer. At least one of these symptoms must be the clear presence of delusions (Criterion Al), hallucinations (Criterion A2), or disorganized speech

(Criterion A3). Grossly disorganized or catatonic behavior (Criterion A4) and negative

symptoms (Criterion A5) may also be present. In those situations in which the activephase symptoms remit within a month in response to treatment. Criterion A is still met if the

clinician estimates that they would have persisted in the absence of treatment.

Schizophrenia involves impairment in one or more major areas of functioning (Criterion B). If the disturbance begins in childhood or adolescence, the expected level of function is not attained. Comparing the individual with unaffected siblings may be helpful. The

dysfunction persists for a substantial period during the course of the disorder and does not

appear to be a direct result of any single feature. Avolition (i.e., reduced drive to pursue

goal-directed behavior; Criterion A5) is linked to the social dysfunction described under

Criterion B. There is also strong evidence for a relationship between cognitive impairment

(see the section "Associated Features Supporting Diagnosis" for this disorder) and functional impairment in individuals with schizophrenia.

Some signs of the disturbance must persist for a continuous period of at least 6 months

(Criterion C). Pi;odromal symptoms often precede the active phase, and residual symptoms may follow it, characterized by mild or subthreshold forms of hallucinations or

delusions. Individuals may express a variety of unusual or odd beliefs that are not of delusional proportions (e.g., ideas of reference or magical thinking); they may have unusual

perceptual experiences (e.g., sensing the presence of an unseen person); their speech may

be generally understandable but vague; and their behavior may be unusual but not grossly

disorganized (e.g., mumbling in public). Negative symptoms are common in the prodromal and residual phases and can be severe. Individuals who had been socially active

may become withdrawn from previous routines. Such behaviors are often the first sign of

a disorder.

Mood symptoms and full mood episodes are common in schizophrenia and may be concurrent with active-phase symptomatology. However, as distinct from a psychotic mood disorder, a schizophrenia diagnosis requires the presence of delusions or hallucinations in the

absence of mood episodes. In addition, mood episodes, taken in total, should be present for

only a minority of the total duration of the active and residual periods of the illness.

In addition to the five symptom domain areas identified in the diagnostic criteria, the

assessment of cognition, depression, and mania symptom domains is vital for making critically important distinctions between the various schizophrenia spectrum and other psychotic disorders.

Associated Features Supporting Diagnosis

Individuals with schizophrenia may display inappropriate affect (e.g., laughing in the absence of an appropriate stimulus); a dysphoric mood that can take the form of depression,

anxiety, or anger; a disturbed sleep pattern (e.g., daytime sleeping and nighttime activity);

and a lack of interest in eating or food refusal. Depersonalization, derealization, and somatic concerns may occur and sometimes reach delusional proportions. Anxiety and phobias are common. Cognitive deficits in schizophrenia are conrmion and are strongly linked

to vocational and functional impairments. These deficits can include decrements in declarative memory, working memory, language function, and other executive functions, as well

as slower processing speed. Abnormalities in sensory processing and inhibitory capacity,

as well as reductions in attention, are also found. Some individuals with schizophrenia

show social cognition deficits, including deficits in the ability to infer the intentions of

other people (theory of mind), and may attend to and then inteφret irrelevant events or

stimuli as meaningful, perhaps leading to the generation of explanatory delusions. These

impairments frequently persist during symptomatic remission.

Some individuals with psychosis may lack insight or awareness of their disorder (i.e.,

anosognosia). This lack of "'insight" includes unawareness of symptoms of schizophrenia

and may be present throughout the entire course of the illness. Unawareness of illness is

typically a symptom of schizophrenia itself rather than a coping strategy. It is comparable

to the lack of awareness of neurological deficits following brain damage, termed anosognosia. This symptom is the most common predictor of non-adherence to treatment, and it

predicts higher relapse rates, increased number of involuntary treatments, poorer psychosocial functioning, aggression, and a poorer course of illness.

Hostility and aggression can be associated with schizophrenia, although spontaneous

or random assault is uncommon. Aggression is more frequent for younger males and for

individuals with a past history of violence, non-adherence with treatment, substance

abuse, and impulsivity. It should be noted that the vast majority of persons with schizophrenia are not aggressive and are more frequently victimized than are individuals in the

general population.

Currently, there are no radiological, laboratory, or psychometric tests for the disorder.

Differences are evident in multiple brain regions between groups of healthy individuals

and persons with schizophrenia, including evidence from neuroimaging, neuropathological, and neurophysiological studies. Differences are also evident in cellular architecture,

white matter connectivity, and gray matter volume in a variety of regions such as the prefrontal and temporal cortices. Reduced overall brain volume has been observed, as well as

increased brain volume reduction with age. Brain volume reductions with age are more

pronounced in individuals with schizophrenia than in healthy individuals. Finally, individuals with schizophrenia appear to differ from individuals without the disorder in eyetracking and electrophysiological indices.

Neurological soft signs common in individuals with schizophrenia include impairments

in motor coordination, sensory integration, and motor sequencing of complex movements;

left-right confusion; and disinhibition of associated movements. In addition, minor physical anomalies of the face and limbs may occur.

Prevalence

The lifetime prevalence of schizophrenia appears to be approximately 0.3%-0.7%, although there is reported variation by race/ethnicity, across countries, and by geographic

origin for immigrants and children of immigrants. The sex ratio differs across samples and

populations: for example, an emphasis on negative symptoms and longer duration of disorder (associated with poorer outcome) shows higher incidence rates for males, whereas

definitions allowing for the inclusion of more mood symptoms and brief presentations

(associated with better outcome) show equivalent risks for both sexes.

Development and Course

The psychotic features of schizophrenia typically emerge between the late teens and the

mid-30s; onset prior to adolescence is rare. The peak age at onset for the first psychotic episode is in the early- to mid-20s for males and in the late-20s for females. The onset may be

abrupt or insidious, but the majority of individuals manifest a slow and gradual development of a variety of clinically significant signs and symptoms. Half of these individuals

complain of depressive symptoms. Earlier age at onset has traditionally been seen as a predictor of worse prognosis. However, the effect of age at onset is likely related to gender,

with males having worse premorbid adjustment, lower educational achievement, more

prominent negative symptoms and cognitive impairment, and in general a worse outcome. Impaired cognition is common, and alterations in cognition are present during development and precede the emergence of psychosis, taking the form of stable cognitive

impairments during adulthood. Cognitive impairments may persist when other symptoms

are in remission and contribute to the disability of the disease.

The predictors of course and outcome are largely unexplained, and course and outcome

may not be reliably predicted. The course appears to be favorable in about 20% of those

with schizophrenia, and a small number of individuals are reported to recover completely.

However, most individuals with schizophrenia still require formal or informal daily living

supports, and many remain chronically ill, with exacerbations and remissions of active

symptoms, while others have a course of progressive deterioration.

Psychotic symptoms tend to diminish over the life course, perhaps in association with

normal age-related declines in dopamine activity. Negative symptoms are more closely related to prognosis than are positive symptoms and tend to be the most persistent. Furthermore, cognitive deficits associated with the illness may not improve over the course of the

illness.

The essential features of schizophrenia are the same in childhood, but it is more difficult to make the diagnosis. In children, delusions and hallucinations may be less elaborate

than in adults, and visual hallucinations are more common and should be distinguished

from normal fantasy play. Disorganized speech occurs in many disorders with childhood

onset (e.g., autism spectrum disorder), as does disorganized behavior (e.g., attention-deficit/

hyperactivity disorder). These symptoms should not be attributed to schizophrenia without due consideration of the more common disorders of childhood. Childhood-onset cases

tend to resemble poor-outcome adult cases, with gradual onset and prominent negative

symptoms. Children who later receive the diagnosis of schizophrenia are more likely to

have experienced nonspecific emotional-behavioral disturbances and psychopathology,

intellectual and language alterations, and subtle motor delays.

Late-onset cases (i.e., onset after age 40 years) are overrepresented by females, who

may have married. Often, the course is characterized by a predominance of psychotic

symptoms with preservation of affect and social functioning. Such late-onset cases can still

meet the diagnostic criteria for schizophrenia, but it is not yet clear whether this is the

same condition as schizophrenia diagnosed prior to mid-life (e.g., prior to age 55 years).

Risk and Prognostic Factors

Environmental. Season of birth has been linked to the incidence of schizophrenia, including late winter/early spring in some locations and summer for the deficit form of the

disease. The incidence of schizophrenia and related disorders is higher for children growing up in an urban environment and for some minority ethnic groups.

Genetic and physiological. There is a strong contribution for genetic factors in determining risk for schizophrenia, although most individuals who have been diagnosed with

schizophrenia have no family history of psychosis. Liability is conferred by a spectrum of

risk alleles, common and rare, with each allele contributing only a small fraction to the total population variance. The risk alleles identified to date are also associated with other

mental disorders, including bipolar disorder, depression, and autism spectrum disorder.

Pregnancy and birth complications with hypoxia and greater paternal age are associated

with a higher risk of schizophrenia for the developing fetus. In addition, other prenatal

and perinatal adversities, including stress, infection, malnutrition, maternal diabetes, and

other medical conditions, have been linked with schizophrenia. However, the vast majority of offspring with these risk factors do not develop schizophrenia.

Culture-Related Diagnostic Issues

Cultural and socioeconomic factors must be considered, particularly when the individual

and the clinician do not share the same cultural and socioeconomic background. Ideas that

appear to be delusional in one culture (e.g., witchcraft) may be commonly held in another.

In some cultures, visual or auditory hallucinations with a religious content (e.g., hearing

God's voice) are a normal part of religious experience. In addition, the assessment of disorganized speech may be made difficult by linguistic variation in narrative styles across

cultures. The assessment of affect requires sensitivity to differences in styles of emotional

expression, eye contact, and body language, which vary across cultures. If the assessment

is conducted in a language that is different from the individual's primary language, care

must be taken to ensure that alogia is not related to linguistic barriers. In certain cultures,

distress may take the form of hallucinations or pseudo-hallucinations and overvalued

ideas that may present clinically similar to true psychosis but are normative to the patient's subgroup.

Gender-Related Diagnostic Issues

A number of features distinguish the clinical expression of schizophrenia in females and

males. The general incidence of schizophrenia tends to be slightly lower in females, particularly among treated cases. The age at onset is later in females, with a second mid-life

peak as described earlier (see the section "Development and Course" for this disorder).

Symptoms tend to be more affect-laden among females, and there are more psychotic

symptoms, as well as a greater propensity for psychotic symptoms to worsen in later life.

Other symptom differences include less frequent negative symptoms and disorganization.

Finally, social functioning tends to remain better preserved in females. There are, however, frequent exceptions to these general caveats.

Suicide Risic

Approximately 5%-6% of individuals with schizophrenia die by suicide, about 20% attempt

suicide on one or more occasions, and many more have significant suicidal ideation. Suicidal

behavior is sometimes in response to command hallucinations to harm oneself or others.

Suicide risk remains high over the whole lifespan for males and females, although it may be

especially high for younger males with comorbid substance use. Other risk factors include

having depressive symptoms or feelings of hopelessness and being unemployed, and the

risk is higher, also, in the period after a psychotic episode or hospital discharge.

Functional Consequences of Schizoplirenia

Schizophrenia is associated with significant social and occupational dysfunction. Making

educational progress and maintaining employment are frequently impaired by avolition

or other disorder manifestations, even when the cognitive skills are sufficient for the tasks

at hand. Most individuals are employed at a lower level than their parents, and most, particularly men, do not marry or have limited social contacts outside of their family.

Differential Diagnosis

Major depressive or bipolar disorder with psychotic or catatonic features. The distinction between schizophrenia and major depressive or bipolar disorder with psychotic

features or with catatonia depends on the temporal relationship between the mood disturbance and the psychosis, and on the severity of the depressive or manic symptoms. If delusions or hallucinations occur exclusively during a major depressive or manic episode,

the diagnosis is depressive or bipolar disorder with psychotic features.

Schizoaffective disorder. A diagnosis of schizoaffective disorder requires that a major

depressive or manic episode occur concurrently with the active-phase symptoms and that

the mood symptoms be present for a majority of the total duration of the active periods.

Schizophreniform disorder and brief psychotic disorder. These disorders are of shorter

duration than schizophrenia as specified in Criterion C, which requires 6 months of symptoms. In schizophreniform disorder, the disturbance is present less than 6 months, and in

brief psychotic disorder, symptoms are present at least 1 day but less than 1 month.

Delusional disorder. Delusional disorder can be distinguished from schizophrenia by

the absence of the other symptoms characteristic of schizophrenia (e.g., delusions, prominent auditory or visual hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms).

Schizotypal personality disorder. Schizotypal personality disorder may be distinguished

from schizophrenia by subthreshold symptoms that are associated with persistent personality features.

Obsessive-compulsive disorder and body dysmorphic disorder. Individuals with

obsessive-compulsive disorder and body dysmorphic disorder may present with poor or

absent insight, and the preoccupations may reach delusional proportions. But these

disorders are distinguished from schizophrenia by their prominent obsessions, compulsions, preoccupations with appearance or body odor, hoarding, or body-focused repetitive behaviors.

Posttraumatic stress disorder. Posttraumatic stress disorder may include flashbacks that

have a hallucinatory quality, and hypervigilance may reach paranoid proportions. But a trau-

matic event and characteristic symptom features relating to reliving or reacting to the event

are required to make the diagnosis.

Autism spectrum disorder or communication disorders. These disorders may also have

symptoms resembling a psychotic episode but are distinguished by their respective deficits in social interaction with repetitive and restricted behaviors and other cognitive and

communication deficits. An individual v^ith autism spectrum disorder or communication

disorder must have symptoms that meet full criteria for schizophrenia, w^ith prominent

hallucinations or delusions for at least 1 month, in order to be diagnosed with schizophrenia as a comorbid condition.

Other mental disorders associated with a psychotic episode. The diagnosis of schizophrenia is made only when the psychotic episode is persistent and not attributable to the

physiological effects of a substance or another medical condition. Individuals with a delirium or major or minor neurocognitive disorder may present with psychotic symptoms,

but these would have a temporal relationship to the onset of cognitive changes consistent

with those disorders. Individuals with substance/medication-induced psychotic disorder

may present with symptoms characteristic of Criterion A for schizophrenia, but the substance/medication-induced psychotic disorder can usually be distinguished by the chronological relationship of substance use to the onset and remission of the psychosis in the

absence of substance use.

Comorbidity

Rates of comorbidity with substance-related disorders are high in schizophrenia. Over

half of individuals with schizophrenia have tobacco use disorder and smoke cigarettes

regularly. Comorbidity with anxiety disorders is increasingly recognized in schizophrenia. Rates of obsessive-compulsive disorder and panic disorder are elevated in individuals

with schizophrenia compared with the general population. Schizotypal or paranoid personality disorder may sometimes precede the onset of schizophrenia.

Life expectancy is reduced in individuals with schizophrenia because of associated

medical conditions. Weight gain, diabetes, metabolic syndrome, and cardiovascular and

pulmonary disease are more common in schizophrenia than in the general population.

Poor engagement in health maintenance behaviors (e.g., cancer screening, exercise) increases the risk of chronic disease, but other disorder factors, including medications, lifestyle, cigarette smoking, and diet, may also play a role. A shared vulnerability for

psychosis and medical disorders may explain some of the medical comorbidity of schizophrenia.

Schizoaffective Disorder

Diagnostic Criteria

A. An uninterrupted period of illness during which there is a major mood episode (major

depressive or manic) concurrent with Criterion A of schizophrenia.

Note: The major depressive episode must include Criterion A1 : Depressed mood.

B. Delusions or hallucinations for 2 or more weeks in the absence of a major mood episode (depressive or manic) during the lifetime duration of the illness.

C. Symptoms that meet criteria for a major mood episode are present for the majority of

the total duration of the active and residual portions of the illness.

D. The disturbance is not attributable to the effects of a substance (e.g., a drug of abuse,

a medication) or another medical condition.

Specify whether:

295.70 (F25.0) Bipolar type: This subtype applies if a manic episode is part of the presentation. Major depressive episodes may also occur.

295.70 (F25.1) Depressive type: This subtype applies if only major depressive episodes are part of the presentation.

Specify if:

With catatonia (refer to the criteria for catatonia associated with another mental disorder,

pp. 119-120, for definition).

Coding note: Use additional code 293.89 (F06.1) catatonia associated with

schizoaffective disorder to indicate the presence of the comorbid catatonia.

Specify if:

The following course specifiers are only to be used after a 1 -year duration of the disorder

and if they are not in contradiction to the diagnostic course criteria.

First episode, currently in acute episode: First manifestation of the disorder meeting the defining diagnostic symptom and time criteria. An acute episode is a time period in which the symptom criteria are fulfilled.

First episode, currently in partial remission: Partial remission is a time period during which an improvement after a previous episode is maintained and in which the defining criteria of the disorder are only partially fulfilled.

First episode, currently in full remission: Full remission is a period of time after a

previous episode during which no disorder-specific symptoms are present.

Multiple episodes, currently in acute episode: Multiple episodes may be determined after a minimum of two episodes (i.e., after a first episode, a remission and a

minimum of one relapse).

Multiple episodes, currently in partial remission

Multiple episodes, currently in full remission

Continuous: Symptoms fulfilling the diagnostic symptom criteria of the disorder are

remaining for the majority of the illness course, with subthreshold symptom periods being very brief relative to the overall course.

Unspecified

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, and negative symptoms. Each of these symptoms may be rated for its current

severity (most severe in the last 7 days) on a 5-point scale ranging from 0 (not present)

to 4 (present and severe). (See Clinician-Rated Dimensions of Psychosis Symptom

Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of schizoaffective disorder can be made without using this severity

specifier.

Note: For additional information on Development and Course (age-related factors). Risk

and Prognostic Factors (environmental risk factors), Culture-Related Diagnostic Issues,

and Gender-Related Diagnostic Issues, see the corresponding sections in schizophrenia,

bipolar I and II disorders, and major depressive disorder in their respective chapters.

Diagnostic Features

The diagnosis of schizoaffective disorder is based on the assessment of an uninterrupted

period of illness during which the individual continues to display active or residual symptoms of psychotic illness. The diagnosis is usually, but not necessarily, made during the

period of psychotic illness. At some time during the period. Criterion A for schizophrenia

has to be met. Criteria B (social dysfunction) and F (exclusion of autism spectrum disorder

or other commimication disorder of childhood onset) for schizophrenia do not have to be

met. In addition to meeting Criterion A for schizophrenia, there is a major mood episode

(major depressive or manic) (Criterion A for schizoaffective disorder). Because loss of interest or pleasure is common in schizophrenia, to meet Criterion A for schizoaffective disorder, the major depressive episode must include pervasive depressed mood (i.e., the

presence of markedly diminished interest or pleasure is not sufficient). Episodes of depression or mania are present for the majority of the total duration of the illness (i.e., after

Criterion A has been met) (Criterion C for schizoaffective disorder). To separate schizoaffective disorder from a depressive or bipolar disorder with psychotic features, delusions

or hallucinations must be present for at least 2 w^eeks in the absence of a major mood episode (depressive or manic) at some point during the lifetime duration of the illness (Criterion B for schizoaffective disorder). The symptoms must not be attributable to the effects

of a substance or another medical condition (Criterion D for schizoaffective disorder).

Criterion C for schizoaffective disorder specifies that mood symptoms meeting criteria

for a major mood episode must be present for the majority of the total duration of the active and residual portion of the illness. Criterion C requires the assessment of mood symptoms for the entire course of a psychotic illness, which differs from the criterion in DSM-IV,

which required only an assessment of the current period of illness. If the mood symptoms

are present for only a relatively brief period, the diagnosis is schizophrenia, not schizoaffective disorder. When deciding whether an individual's presentation meets Criterion C,

the clinician should review the total duration of psychotic illness (i.e., both active and residual symptoms) and determine when significant mood symptoms (untreated or in need

of treatment with antidepressant and/or mood-stabilizing medication) accompanied the

psychotic symptoms. This determination requires sufficient historical information and

clinical judgment. For example, an individual with a 4-year history of active and residual

symptoms of schizophrenia develops depressive and manic episodes that, taken together,

do not occupy more than 1 year during the 4-year history of psychotic illness. This presentation would not meet Criterion C.

In addition to the five symptom domain areas identified in the diagnostic criteria, the

assessment of cognition, depression, and mania symptom domains is vital for making critically important distinctions between the various schizophrenia spectrum and other psychotic disorders.

Associated Features Supporting Diagnosis

Occupational functioning is frequently impaired, but this is not a defining criterion (in

contrast to schizophrenia). Restricted social contact and difficulties with self-care are associated with schizoaffective disorder, but negative symptoms may be less severe and less

persistent than those seen in schizophrenia. Anosognosia (i.e., poor insight) is also common in schizoaffective disorder, but the deficits in insight may be less severe and pervasive than those in schizophrenia. Individuals with schizoaffective disorder may be at

increased risk for later developing episodes of major depressive disorder or bipolar disorder if mood symptoms continue following the remission of symptoms meeting Criterion A

for schizophrenia. There may be associated alcohol and other substance-related disorders.

There are no tests or biological measures that can assist in making the diagnosis of

schizoaffective disorder. Whether schizoaffective disorder differs from schizophrenia

with regard to associated features such as structural or functional brain abnormalities,

cognitive deficits, or genetic risk factors is not clear.

Prevalence

Schizoaffective disorder appears to be about one-third as common as schizophrenia. Lifetime prevalence of schizoaffective disorder is estimated to be 0.3%. The incidence of

schizoaffective disorder is higher in females than in males, mainly due to an increased incidence of the depressive type among females.

Development and Course

The typical age at onset of schizoaffective disorder is early adulthood, although onset can

occur anywhere from adolescence to late in life. A significant number of individuals diagnosed with another psychotic illness initially will receive the diagnosis schizoaffective disorder later when the pattern of mood episodes has become more apparent. With the

current diagnostic Criterion C, it is expected that the diagnosis for some individuals will

convert from schizoaffective disorder to another disorder as mood symptoms become less

prominent. The prognosis for schizoaffective disorder is somewhat better than the prognosis for schizophrenia but worse than the prognosis for mood disorders.

Schizoaffective disorder may occur in a variety of temporal patterns. The following is

a typical pattern: An individual may have pronounced auditory hallucinations and persecutory delusions for 2 months before the onset of a prominent major depressive episode.

The psychotic symptoms and the full major depressive episode are then present for 3 months.

Then, the individual recovers completely from the major depressive episode, but the psychotic symptoms persist for another month before they too disappear. During this period

of illness, the individual's symptoms concurrently met criteria for a major depressive episode and Criterion A for schizophrenia, and during this same period of illness, auditory

hallucinations and delusions were present both before and after the depressive phase. The

total period of illness lasted for about 6 months, with psychotic symptoms alone present

during the initial 2 months, both depressive and psychotic symptoms present during the

next 3 months, and psychotic symptoms alone present during the last month. In this instance, the duration of the depressive episode was not brief relative to the total duration of

the psychotic disturbance, and thus the presentation qualifies for a diagnosis of schizoaffective disorder.

The expression of psychotic symptoms across the lifespan is variable. Depressive or

manic symptoms can occur before the onset of psychosis, during acute psychotic episodes,

during residual periods, and after cessation of psychosis. For example, an individual

might present with prominent mood symptoms during the prodromal stage of schizophrenia. This pattern is not necessarily indicative of schizoaffective disorder, since it is the

co-occurrence of psychotic and mood symptoms that is diagnostic. For an individual with

symptoms that clearly meet the criteria for schizoaffective disorder but who on further follow-up only presents with residual psychotic symptoms (such as subthreshold psychosis

and/or prominent negative symptoms), the diagnosis may be changed to schizophrenia,

as the total proportion of psychotic illness compared with mood symptoms becomes more

prominent. Schizoaffective disorder, bipolar type, may be more common in young adults,

whereas schizoaffective disorder, depressive type, may be more common in older adults.

Risk and Prognostic Factors

Genetic and physiological. Among individuals with schizophrenia, there may be an increased risk for schizoaffective disorder in first-degree relatives. The risk for schizoaffective disorder may be increased among individuals who have a first-degree relative with

schizophrenia, bipolar disorder, or schizoaffective disorder.

Culture-Reiated Diagnostic Issues

Cultural and socioeconomic factors must be considered, particularly when the individual

and the clinician do not share the same cultural and economic background. Ideas that appear to be delusional in one culture (e.g., witchcraft) may be commonly held in another.

There is also some evidence in the literature for the overdiagnosis of schizophrenia com­

pared with schizoaffective disorder in African American and Hispanic populations, so

care must be tal^en to ensure a culturally appropriate evaluation that includes both psychotic and affective symptoms.

Suicide Risic

The lifetime risk of suicide for schizophrenia and schizoaffective disorder is 5%, and the

presence of depressive symptoms is correlated w^ith a higher risk for suicide. There is evidence that suicide rates are higher in North American populations than in European,

Eastern European, South American, and Indian populations of individuals with schizophrenia or schizoaffective disorder.

Functional Consequences of Scliizoaffective Disorder

Schizoaffective disorder is associated with social and occupational dysfunction, but dysfunction is not a diagnostic criterion (as it is for schizophrenia), and there is substantial

variability between individuals diagnosed with schizoaffective disorder.

Differential Diagnosis

Other mental disorders and medical conditions. A wide variety of psychiatric and medical conditions can manifest with psychotic and mood symptoms that must be considered

in the differential diagnosis of schizoaffective disorder. These include psychotic disorder

due to another medical condition; delirium; major neurocognitive disorder; substance/

medication-induced psychotic disorder or neurocognitive disorder; bipolar disorders

with psychotic features; major depressive disorder with psychotic features; depressive or

bipolar disorders with catatonic features; schizotypal, schizoid, or paranoid personality

disorder; brief psychotic disorder; schizophreniform disorder; schizophrenia; delusional

disorder; and other specified and unspecified schizophrenia spectrum and other psychotic

disorders. Medical conditions and substance use can present with a combination of psychotic and mood symptoms, and thus psychotic disorder due to another medical condition

needs to be excluded. Distinguishing schizoaffective disorder from schizophrenia and

from depressive and bipolar disorders with psychotic features is often difficult. Criterion

C is designed to separate schizoaffective disorder from schizophrenia, and Criterion B is

designed to distinguish schizoaffective disorder from a depressive or bipolar disorder

with psychotic features. More specifically, schizoaffective disorder can be distinguished

from a depressive or bipolar disorder with psychotic features due to the presence of prominent delusions and/or hallucinations for at least 2 weeks in the absence of a major mood

episode. In contrast, in depressive or bipolar disorders with psychotic features, the psychotic features primarily occur during the mood episode(s). Because the relative proportion of mood to psychotic symptoms may change over time, the appropriate diagnosis

may change from and to schizoaffective disorder (e.g., a diagnosis of schizoaffective disorder for a severe and prominent major depressive episode lasting 3 months during the

first 6 months of a persistent psychotic illness would be changed to schizophrenia if active

psychotic or prominent residual symptoms persist over several years without a recurrence

of another mood episode).

Psychotic disorder due to another medical condition. Other medical conditions and

substance use can manifest with a combination of psychotic and mood symptoms, and

thus psychotic disorder due to another medical condition needs to be excluded.

Schizophrenia, bipolar, and depressive disorders. Distinguishing schizoaffective disorder from schizophrenia and from depressive and bipolar disorders with psychotic features is often difficult. Criterion C is designed to separate schizoaffective disorder from

schizophrenia, and Criterion B is designed to distinguish schizoaffective disorder from a

depressive or bipolar disorder with psychotic features. More specifically, schizoaffective

disorder can be distinguished from a depressive or bipolar disorder with psychotic features

based on the presence of prominent delusions and/or hallucinations for at least 2 weeks in

the absence of a major mood episode. In contrast, in depressive or bipolar disorder with

psychotic features, the psychotic features primarily occur during the mood episode(s). Because the relative proportion of mood to psychotic symptoms may change over time, the

appropriate diagnosis may change from and to schizoaffective disorder. (For example, a

diagnosis of schizoaffective disorder for a severe and prominent major depressive episode

lasting 3 months during the first 6 months of a chronic psychotic illness would be changed

to schizophrenia if active psychotic or prominent residual symptoms persist over several

years without a recurrence of another mood episode.)

Comorbidity

Many individuals diagnosed with schizoaffective disorder are also diagnosed with other

mental disorders, especially substance use disorders and anxiety disorders. Similarly, the

incidence of medical conditions is increased above base rate for the general population

and leads to decreased life expectancy.

Substance/Medication-Induced

Psychotic Disorder

Diagnostic Criteria

A. Presence of one or both of the following symptoms:

1. Delusions.

2. Hallucinations.

B. There is evidence from the history, physical examination, or laboratory findings of both

(1)and (2):

1. The symptoms in Criterion A developed during or soon after substance intoxication

or withdrawal or after exposure to a medication.

2. The involved substance/medication is capable of producing the symptoms in Criterion A.

C. The disturbance is not better explained by a psychotic disorder that is not substance/

medication-induced. Such evidence of an independent psychotic disorder could include the following:

The symptoms preceded the onset of the substance/medication use; the symptoms

persist for a substantial period of time (e.g., about 1 month) after the cessation of

acute withdrawal or severe intoxication: or there is other evidence of an independent non-substance/medication-induced psychotic disorder (e.g., a history of recurrent non-substance/medication-related episodes).

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Note: This diagnosis should be made instead of a diagnosis of substance intoxication or

substance withdrawal only when the symptoms in Criterion A predominate in the clinical

picture and when they are sufficiently severe to warrant clinical attention.

Coding note: The ICD-9-CM and ICD-10-CIVI codes for the [specific substance/medication]-induced psychotic disorders 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-induced psychotic disorder, the 4th position character is “1 and the clinician should

record “mild [substance] use disorder” before the substance-induced psychotic disorder

(e.g., “mild cocaine use disorder with cocaine-induced psychotic disorder”). If a moderate or

severe substance use disorder is comorbid with the substance-induced psychotic 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 (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-induced psychotic disorder.

ICD-10-CM

ICD-9-CM

With use

disorder,

mild

With use

disorder,

moderate

or severe

Without

use

disorder

Alcohol 291.9 F10.159 FI 0.259 FI 0.959

Cannabis 292.9 F12.159 FI 2.259 FI 2.959

Phencyclidine 292.9 F16.159 FI 6.259 FI 6.959

Other hallucinogen 292.9 FI 6.159 FI 6.259 FI 6.959

Inhalant 292.9 F18.159 FI 8.259 FI 8.959

Sedative, hypnotic, or

anxiolytic

292.9 FI 3.159 FI 3.259 FI 3.959

Amphetamine (or other

stimulant)

292.9 FI 5.159 FI 5.259 FI 5.959

Cocaine 292.9 F14.159 FI 4.259 FI 4.959

Other (or unknown) substance 292.9 FI 9.159 FI 9.259 FI 9.959

Specify if (see Table 1 in the chapter “Substance-Related and Addictive Disorders” for diagnoses associated with substance class):

With onset during intoxication: If the criteria are met for intoxication with the substance and the symptoms develop during intoxication.

With onset during withdrawal: If the criteria are met for withdrawal from the substance and the symptoms develop during, or shortly after, withdrawal.

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, abnormal psychomotor behavior, and negative

symptoms. Each of these symptoms may be rated for its current severity (most severe

in the last 7 days) on a 5-point scale ranging from 0 (not present) to 4 (present and

severe). (See Clinician-Rated Dimensions of Psychosis Symptom Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of substance/medication-induced psychotic disorder can be made

without using this severity specifier.

Recording Procedures

ICD-9-CM. The name of the substance/medication-induced psychotic disorder begins

with the specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing

the delusions or hallucinations. 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 specification of onset (i.e., onset during intoxication, onset during withdrawal). Unlike the recording procedures for ICD-IO-CM,

which combine the substance-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 delusions occurring during intoxication in a man with a severe cocaine use disorder, the diagnosis is 292.9 cocaine-induced psychotic disorder, with onset

during intoxication. An additional diagnosis of 304.20 severe cocaine use disorder is also

given. When more than one substance is judged to play a significant role in the development

of psychotic symptoms, each should be listed separately (e.g., 292.9 cannabis-induced psychotic disorder with onset during intoxication, with severe cannabis use disorder; 292.9

phencyclidine-induced psychotic disorder, with onset during intoxication, with mild

phencyclidine use disorder).

ICD-10-CM. The name of the substance/medication-induced psychotic disorder begins

with the specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing

the delusions or hallucinations. 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" with no comorbid substance use 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" with no comorbid substance use 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-induced

psychotic disorder, followed by the specification of onset (i.e., onset during intoxication,

onset during withdrawal). For example, in the case of delusions occurring during intoxication in a man with a severe cocaine use disorder, the diagnosis is F14.259 severe cocaine

use disorder with cocaine-induced psychotic disorder, with onset during intoxication. A

separate diagnosis of the comorbid severe cocaine use disorder is not given. If the substance-induced psychotic disorder 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., F16.959 phencyclidine-induced psychotic disorder, with onset during intoxication). When more than one substance is judged to play a significant role in the

development of psychotic symptoms, each should be listed separately (e.g., F12.259 severe

cannabis use disorder with cannabis-induced psychotic disorder, with onset during intoxication; F16.159 mild phencyclidine use disorder with phencyclidine-induced psychotic

disorder, with onset during intoxication).

Diagnostic Features

The essential features of substance/medication-induced psychotic disorder are prominent

delusions and/or hallucinations (Criterion A) that are judged to be due to the physiological effects of a substance/medication (i.e., a drug of abuse, a medication, or a toxin exposure) (Criterion B). Hallucinations that the individual realizes are substance/medicationinduced are not included here and instead would be diagnosed as substance intoxication

or substance withdrawal with the accompanying specifier "with perceptual disturbances"

(applies to alcohpl withdrawal; cannabis intoxication; sedative, hypnotic, or anxiolytic

withdrawal; and stimulant intoxication).

A substance/medication-induced psychotic disorder is distinguished from a primary

psychotic disorder by considering the onset, course, and other factors. For drugs of abuse,

there must be evidence from the history, physical examination, or laboratory findings of

substance use, intoxication, or withdrawal. Substance/medication-induced psychotic

disorders arise during or soon after exposure to a medication or after substance intoxication or withdrawal but can persist for weeks, whereas primary psychotic disorders may

precede the onset of substance/medication use or may occur during times of sustained abstinence. Once initiated, the psychotic symptoms may continue as long as the substance/

medication use continues. Another consideration is the presence of features that are atypical of a primary psychotic disorder (e.g., atypical age at onset or course). For example, the

appearance of delusions de novo in a person older than 35 years without a known history

of a primary psychotic disorder should suggest the possibility of a substance/medicationinduced psychotic disorder. Even a prior history of a primary psychotic disorder does not

rule out the possibility of a substance/medication-induced psychotic disorder. In contrast,

factors that suggest that the psychotic symptoms are better accounted for by a primary

psychotic disorder include persistence of psychotic symptoms for a substantial period of

time (i.e., a month or more) after the end of substance intoxication or acute substance withdrawal or after cessation of medication use; or a history of prior recurrent primary psychotic disorders. Other causes of psychotic symptoms must be considered even in an

individual with substance intoxication or withdrawal, because substance use problems are

not uncommon among individuals with non-substance/medication-induced psychotic

disorders.

In addition to the four symptom domain areas identified in the diagnostic criteria, the

assessment of cognition, depression, and mania symptom domains is vital for making critically important distinctions between the various schizophrenia spectrum and other psychotic disorders.

Associated Features Supporting Diagnosis

Psychotic disorders can occur in association with intoxication with the following classes of

substances: alcohol; cannabis; hallucinogens, including phencyclidine and related substances; inhalants; sedatives, hypnotics, and anxiolytics; stimulants (including cocaine);

and other (or unknown) substances. Psychotic disorders can occur in association with withdrawal from the following classes of substances: alcohol; sedatives, hypnotics, and anxiolytics; and other (or unknown) substances.

Some of the medications reported to evoke psychotic symptoms include anesthetics

and analgesics, anticholinergic agents, anticonvulsants, antihistamines, antihypertensive

and cardiovascular medications, antimicrobial medications, antiparkinsonian medications, chemotherapeutic agents (e.g., cyclosporine, procarbazine), corticosteroids, gastrointestinal medications, muscle relaxants, nonsteroidal anti-inflammatory medications,

other over-the-counter medications (e.g., phenylephrine, pseudoephedrine), antidepressant medication, and disulfiram. Toxins reported to induce psychotic symptoms include

anticholinesterase, organophosphate insecticides, sarin and other nerve gases, carbon

monoxide, carbon dioxide, and volatile substances such as fuel or paint.

Prevaience

Prevalence of substance/medication-induced psychotic disorder in the general population is unknown. Between 7% and 25% of individuals presenting with a first episode of

psychosis in different settings are reported to have substance/medication-induced psychotic disorder.

Development and Course

The initiation of the disorder may vary considerably with the substance. For example,

smoking a high dose of cocaine may produce psychosis within minutes, whereas days or

weeks of high-dose alcohol or sedative use may be required to produce psychosis. Alcohol-induced psychotic disorder, with hallucinations, usually occurs only after prolonged,

heavy ingestion of alcohol in individuals who have moderate to severe alcohol use disorder,

and the hallucinations are generally auditory in nature.

Psychotic disorders induced by amphetamine and cocaine share similar clinical features. Persecutory delusions may rapidly develop shortly after use of amphetamine or a

similarly acting sympathomimetic. The hallucination of bugs or vermin crawling in or under the skin (formication) can lead to scratching and extensive skin excoriations. Cannabisinduced psychotic disorder may develop shortly after high-dose cannabis use and usually

involves persecutory delusions, marked anxiety, emotional lability, and depersonalization.

The disorder usually remits within a day but in some cases may persist for a few days.

Substance/medication-induced psychotic disorder may at times persist when the offending agent is removed, such that it may be difficult initially to distinguish it from an independent psychotic disorder. Agents such as amphetamines, phencyclidine, and cocaine have been

reported to evoke temporary psychotic states that can sometimes persist for weeks or longer

despite removal of the agent and treatment with neuroleptic medication. In later life, polypharmacy for medical conditions and exposure to medications for parkinsonism, cardiovascular disease, and other medical disorders may be associated with a greater likelihood of

psychosis induced by prescription medications as opposed to substances of abuse.

Diagnostic iVlarlcers

With substances for which relevant blood levels are available (e.g., blood alcohol level,

other quantifiable blood levels such as digoxin), the presence of a level consistent with toxicity may increase diagnostic certainty.

Functionai Consequences of

Substance/iVledication-induced Psycliotic Disorder

Substance/medication-induced psychotic disorder is typically severely disabling and

consequently is observed most frequently in emergency rooms, as individuals are often

brought to the acute-care setting when it occurs. However, the disability is typically selflimited and resolves upon removal of the offending agent.

Differential Diagnosis

Substance intoxication or substance withdrawal. Individuals intoxicated with stimulants, cannabis, the opioid meperidine, or phencyclidine, or those withdrawing from alcohol or sedatives, may experience altered perceptions that they recognize as drug effects. If

reality testing for these experiences remains intact (i.e., the individual recognizes that the

perception is substance induced and neither believes in nor acts on it), the diagnosis is not

substance/medication-induced psychotic disorder. Instead, substance intoxication or

substance withdrawal, with perceptual disturbances, is diagnosed (e.g., cocaine intoxication, with perceptual disturbances). "Flashback" hallucinations that can occur long after

the use of hallucinogens has stopped are diagnosed as hallucinogen persisting perception

disorder. If substance/medication-induced psychotic symptoms occur exclusively during

the course of a delirium, as in severe forms of alcohol withdrawal, the psychotic symptoms

are considered to be an associated feature of the delirium and are not diagnosed separately. Delusions in the context of a major or mild neurocognitive disorder would be diagnosed as major or mild neurocognitive disorder, with behavioral disturbance.

Primary psychotic disorder. A substance/medication-induced psychotic disorder is

distinguished from a primary psychotic disorder, such as schizophrenia, schizoaffective

disorder, delusional disorder, brief psychotic disorder, other specified schizophrenia

spectrum and other psychotic disorder, or unspecified schizophrenia spectrum and other

psychotic disorder, by the fact that a substance is judged to be etiologically related to the

symptoms.

Psychotic disorder due to another medical condition. A substance/medication-induced

psychotic disorder due to a prescribed treatment for a mental or medical condition must

have its onset while the individual is receiving the medication (or during withdrawal, if

there is a withdrawal syndrome associated with the medication). Because individuals with

medical conditions often take medications for those conditions, the clinician must consider the possibility that the psychotic symptoms are caused by the physiological consequences of the medical condition rather than the medication, in which case psychotic

disorder due to another medical condition is diagnosed. The history often provides the

primary basis for such a judgment. At times, a change in the treatment for the medical condition (e.g., medication substitution or discontinuation) may be needed to determine empirically for that individual whether the medication is the causative agent. If the clinician

has ascertained that the disturbance is attributable to both a medical condition and substance/medication use, both diagnoses (i.e., psychotic disorder due to another medical

condition and substance/medication-induced psychotic disorder) may be given.

Psychotic Disorder

Due to Another Medical Condition

Diagnostic Criteria

A. Prominent hallucinations or delusions.

B. There is evidence from the history, physical examination, or laboratory findings that the

disturbance is the direct pathophysiological consequence of another medical condition.

C. The disturbance is not better explained by another mental disorder.

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Specify whether:

Code based on predominant symptom:

293.81 (F06.2) With delusions: If delusions are the predominant symptom.

293.82 (F06.0) With hallucinations: If hallucinations are the predominant symptom.

Coding note: Include the name of the other medical condition in the name of the mental

disorder (e.g., 293.81 [F06.2] psychotic disorder due to malignant lung neoplasm, with delusions). The other medical condition should be coded and listed separately immediately

before the psychotic disorder due to the medical condition (e.g., 162.9 [C34.90] malignant

lung neoplasm; 293.81 [F06.2] psychotic disorder due to malignant lung neoplasm, with

delusions).

Specify current severity:

Severity is rated by a quantitative assessment of the primary symptoms of psychosis,

including delusions, hallucinations, abnormal psychomotor behavior, and negative

symptoms. Each of these symptoms may be rated for its current severity (most severe

in the last 7 days) on a 5-point scale ranging from 0 (not present) to 4 (present and

severe). (See Clinician-Rated Dimensions of Psychosis Symptom Severity in the chapter “Assessment Measures.”)

Note: Diagnosis of psychotic disorder due to another medical condition can be made

without using this severity specifier.

Specifiers

In addition to the symptom domain areas identified in the diagnostic criteria, the assessment of cognition, depression, and mania symptom domains is vital for making critically

important distinctions between the various schizophrenia spectrum and other psychotic

disorders.

Diagnostic Features

The essential features of psychotic disorder due to another medical condition are prominent delusions or hallucinations that are judged to be attributable to the physiological effects of another medical condition and are not better explained by another mental disorder

(e.g., the symptoms are not a psychologically mediated response to a severe medical condition, in which case a diagnosis of brief psychotic disorder, with marked stressor, would

be appropriate).

Hallucinations can occur in any sensory modality (i.e., visual, olfactory, gustatory, tactile, or auditory), but certain etiological factors are likely to evoke specific hallucinatory

phenomena. Olfactory hallucinations are suggestive of temporal lobe epilepsy. Hallucinations may vary from simple and unformed to highly complex and organized, depending

on etiological and environmental factors. Psychotic disorder due to another medical condition is generally not diagnosed if the individual maintains reality testing for the hallucinations and appreciates that they result from the medical condition. Delusions may have

a variety of themes, including somatic, grandiose, religious, and, most commonly, persecutory. On the whole, however, associations between delusions and particular medical

conditions appear to be less specific than is the case for hallucinations.

In determining whether the psychotic disturbance is attributable to another medical

condition, the presence of a medical condition must be identified and considered to be the

etiology of the psychosis through a physiological mechanism. Although there are no

infallible guidelines for determining whether the relationship between the psychotic disturbance and the medical condition is etiological, several considerations provide some guidance.

One consideration is the presence of a temporal association between the onset, exacerbation, or remission of the medical condition and that of the psychotic disturbance. A second

consideration is the presence of features that are atypical for a psychotic disorder (e.g.,

atypical age at onset or presence of visual or olfactory hallucinations). The disturbance must

also be distinguished from a substance/medication-induced psychotic disorder or another mental disorder (e.g., an adjustment disorder).

Associated Features Supporting Diagnosis

The temporal association of the onset or exacerbation of the medical condition offers the

greatest diagnostic certainty that the delusions or hallucinations are attributable to a medical condition. Additional factors may include concomitant treatments for the underlying

medical condition that confer a risk for psychosis independently, such as steroid treatment

for autoimmune disorders.

Prevalence

Prevalence rates for psychotic disorder due to another medical condition are difficult to estimate given the wide variety of underlying medical etiologies. Lifetime prevalence has

been estimated to range from 0.21% to 0.54%. When the prevalence findings are stratified

by age group, individuals older than 65 years have a significantly greater prevalence of

0.74% compared with those in younger age groups. Rates of psychosis also vary according

to the underlying medical condition; conditions most commonly associated with psychosis include untreated endocrine and metabolic disorders, autoimmune disorders (e.g.,

systemic lupus erythematosus, N-methyl-D-aspartate (NMDA) receptor autoimmune encephalitis), or temporal lobe epilepsy. Psychosis due to epilepsy has been further differentiated into ictal, postictal, and interictal psychosis. The most common of these is postictal

psychosis, observed in 2%-7.8% of epilepsy patients. Among older individuals, there may

be a higher prevalence of the disorder in females, although additional gender-related features are not clear and vary considerably with the gender distributions of the underlying

medical conditions.

Development and Course

Psychotic disorder due to another medical condition may be a single transient state or it

may be recurrent, cycling with exacerbations and remissions of the underlying medical

condition. Although treatment of the underlying medical condition often results in a resolution of the psychosis, this is not always the case, and psychotic symptoms may persist

long after the medical event (e.g., psychotic disorder due to focal brain injury). In the context of chronic conditions such as multiple sclerosis or chronic interictal psychosis of epilepsy, the psychosis may assume a long-term course.

The expression of psychotic disorder due to another medical condition does not differ

substantially in phenomenology depending on age at occurrence. However, older age

groups have a higher prevalence of the disorder, which is most likely due to the increasing

medical burden associated with advanced age and the cumulative effects of deleterious

exposures and age-related processes (e.g., atherosclerosis). The nature of the underlying

medical conditions is likely to change across the lifespan, with younger age groups more

affected by epilepsy, head trauma, autoimmune, and neoplastic diseases of early to midlife, and older age groups more affected by stroke disease, anoxic events, and multiple system comorbidities. Underlying factors with increasing age, such as preexisting cognitive

impairment as well as vision and hearing impairments, may incur a greater risk for psychosis, possibly by serving to lower the threshold for experiencing psychosis.

Risk and Prognostic Factors

Course modifiers. Identification and treatment of the underlying medical condition has

the greatest impact on course, although preexisting central nervous system injury may

confer a worse course outcome (e.g., head trauma, cerebrovascular disease).

Diagnostic iVlarlcers

The diagnosis of psychotic disorder due to another medical condition depends on the clinical condition of each individual, and the diagnostic tests will vary according to that condition. A variety of medical conditions may cause psychotic symptoms. These include

neurological conditions (e.g., neoplasms, cerebrovascular disease, Huntington's disease,

multiple sclerosis, epilepsy, auditory or visual nerve injury or impairment, deafness,

migraine, central nervous system infections), endocrine conditions (e.g., hyper- and hypothyroidism, hyper- and hypoparathyroidism, hyper- and hypoadrenocorticism), metabolic

conditions (e.g., hypoxia, hypercarbia, hypoglycemia), fluid or electrolyte imbalances,

hepatic or renal diseases, and autoimmune disorders with central nervous system involvement (e.g., systemic lupus erythematosus). The associated physical examination findings,

laboratory findings, and patterns of prevalence or onset reflect the etiological medical

condition.

Suicide Risl(

Suicide risk in the context of psychotic disorder due to another medical condition is not

clearly delineated, although certain conditions such as epilepsy and multiple sclerosis are

associated with increased rates of suicide, which may be further increased in the presence

of psychosis.

Functional Consequences of Psycliotic Disorder

Due to Another IVIedical Condition

Functional disability is typically severe in the context of psychotic disorder due to another

medical condition but will vary considerably by the type of condition and likely improve

with successful resolution of the condition.

Differential Diagnosis

Delirium. Hallucinations and delusions commonly occur in the context of a delirium;

however, a separate diagnosis of psychotic disorder due to another medical condition is

not given if the disturbance occurs exclusively during the course of a delirium. Delusions

in the context of a major or mild neurocognitive disorder would be diagnosed as major or

mild neurocognitive disorder, with behavioral disturbance.

Substance/medication-induced psychotic disorder. If there is evidence of recent or

prolonged substance use (including medications with psychoactive effects), withdrawal

from a substance, or exposure to a toxin (e.g., LSD [lysergic acid diethylamide] intoxication, alcohol withdrawal), a substance/medication-induced psychotic disorder should be

considered. Symptoms that occur during or shortly after (i.e., within 4 weeks) of substance

intoxication or withdrawal or after medication use may be especially indicative of a substance-induced psychotic disorder, depending on the character, duration, or amount of

the substance used. If the clinician has ascertained that the disturbance is due to both a

medical condition and substance use, both diagnoses (i.e., psychotic disorder due to another medical condition and substance/medication-induced psychotic disorder) can be

given.

Psychotic disorder. Psychotic disorder due to another medical condition must be distinguished from a psychotic disorder (e.g., schizophrenia, delusional disorder, schizoaffective

disorder) or a depressive or bipolar disorder, with psychotic features. In psychotic disorders and in depressive or bipolar disorders, with psychotic features, no specific and direct

causative physiological mechanisms associated with a medical condition can be demonstrated. Late age at onset and the absence of a personal or family history of schizophrenia

or delusional disorder suggest the need for a thorough assessment to rule out the diagnosis of psychotic disorder due to another medical condition. Auditory hallucinations that

involve voices speaking complex sentences are more characteristic of schizophrenia than

of psychotic disorder due to a medical condition. Other types of hallucinations (e.g., visual, olfactory) commonly signal a psychotic disorder due to another medical condition or

a substance/medication-induced psychotic disorder.

Comorbidity

Psychotic disorder due to another medical condition in individuals older than 80 years is

associated with concurrent major neurocognitive disorder (dementia).

Catatonia

Catatonia can occur in the context of several disorders, including neurodevelopmental,

psychotic, bipolar, depressive disorders, and other medical conditions (e.g., cerebral folate

deficiency, rare autoimmune and paraneoplastic disorders. The manual does not treat

catatonia as an independent class but recognizes a) catatonia associated with another mental disorder (i.e., a neurodevelopmental, psychotic disorder, a bipolar disorder, a depressive disorder, or other mental disorder), b) catatonic disorder due to another medical

condition, and c) unspecified catatonia.

Catatonia is defined by the presence of three or more of 12 psychomotor features in the

diagnostic criteria for catatonia associated with another mental disorder and catatonic disorder due to another medical condition. The essential feature of catatonia is a marked psychomotor disturbance that may involve decreased motor activity, decreased engagement

during interview or physical examination, or excessive and peculiar motor activity. The

clinical presentation of catatonia can be puzzling, as the psychomotor disturbance may

range from marked unresponsiveness to marked agitation. Motoric immobility may be severe (stupor) or moderate (catalepsy and waxy flexibility). Similarly, decreased engagement may be severe (mutism) or moderate (negativism). Excessive and peculiar motor

behaviors can be complex (e.g., stereotypy) or simple (agitation) and may include echolalia and echopraxia. In extreme cases, the same individual may wax and wane between decreased and excessive motor activity. The seemingly opposing clinical features and

variable manifestations of the diagnosis contribute to a lack of awareness and decreased

recognition of catatonia. During severe stages of catatonia, the individual may need careful supervision to avoid self-harm or harming others. There are potential risks from malnutrition, exhaustion, hyperpyrexia and self-inflicted injury.

Catatonia Associated With Another

Mental Disorder (Catatonia Specifier)

293.89 (F06.1)

A. The clinical picture is dominated by three (or more) of the following symptoms:

1. Stupor (i.e., no psychomotor activity; not actively relating to environment).

2. Catalepsy (i.e., passive induction of a posture held against gravity).

3. Waxy flexibility (i.e., slight, even resistance to positioning by examiner).

4. Mutism (i.e., no, or very little, verbal response [exclude if known aphasia]).

5. Negativism (i.e., opposition or no response to instructions or external stimuli).

6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity).

7. Mannerism (i.e., odd, circumstantial caricature of normal actions).

8. Stereotypy (i.e., repetitive, abnormally frequent, non-goal-directed movements).

9. Agitation, not influenced by external stimuli.

10. Grimacing.

11. Echolalia (i.e., mimicking another’s speech).

12. Echopraxia (i.e., mimicking another’s movements).

Coding note: Indicate the name of the associated mental disorder when recording the

name of the condition (i.e., 293.89 [F06.1] catatonia associated with major depressive disorder). Code first the associated mental disorder (e.g., neurodevelopmental disorder, brief

psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder,

bipolar disorder, major depressive disorder, or other mental disorder) (e.g., 295.70 [F25.1]

schizoaffective disorder, depressive type; 293.89 [F06.1] catatonia associated with

schizoaffective disorder).

Diagnostic Features

Catatonia associated with another mental disorder (catatonia specifier) may be used when

criteria are met for catatonia during the course of a neurodevelopmental, psychotic, bipolar, depressive, or other mental disorder. The catatonia specifier is appropriate when the

clinical picture is characterized by marked psychomotor disturbance and involves at least

three of the 12 diagnostic features listed in Criterion A. Catatonia is typically diagnosed in

an inpatient setting and occurs in up to 35% of individuals with schizophrenia, but the majority of catatonia cases involve individuals with depressive or bipolar disorders. Before

the catatonia specifier is used in neurodevelopmental, psychotic, bipolar, depressive, or

other mental disorders, a wide variety of other medical conditions need to be ruled out;

these conditions include, but are not limited to, medical conditions due to infectious, metabolic, or neurological conditions (see '"Catatonic Disorder Due to Another Medical Condition"). Catatonia can also be a side effect of a medication (see the chapter "MedicationInduced Movement Disorders and Other Adverse Effects of Medication"). Because of the

seriousness of the complications, particular attention should be paid to the possibility that

the catatonia is attributable to 333.92 (G21.0) neuroleptic malignant syndrome.

Catatonic Disorder Due to

Another IVIedical Condition

Diagnostic Criteria 293.89 (F06.1)

A. The clinical picture is dominated by three (or more) of the following symptoms:

1. Stupor (i.e., no psychomotor activity; not actively relating to environment).

2. Catalepsy (i.e., passive induction of a posture held against gravity).

3. Waxy flexibility (i.e., slight, even resistance to positioning by examiner).

4. Mutism (i.e., no, or very little, verbal response [Note: not applicable if there is an

established aphasia]).

5. Negativism (i.e., opposition or no response to instructions or external stimuli).

6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity).

7. Mannerism (i.e., odd, circumstantial caricature of normal actions).

8. Stereotypy (i.e., repetitive, abnormally frequent, non-goal-directed movements).

9. Agitation, not influenced by external stimuli.

10. Grimacing.

11. Echolalia (i.e., mimicking another’s speech).

12. Echopraxia (i.e., mimicking another’s movements).

B. There is evidence from the history, physical examination, or laboratory findings that the

disturbance is the direct pathophysiological consequence of another medical condition.

C. The disturbance is not better explained by another mental disorder (e.g., a manic episode).

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Coding note: Include the name of the medical condition in the name of the mental disorder (e.g., 293.89 [F06.1]) catatonic disorder due to hepatic encephalopathy). The other

medical condition should be coded and listed separately immediately before the catatonic disorder due to the medical condition (e.g., 572.2 [K71.90] hepatic encephalopathy;

293.89 [F06.1] catatonic disorder due to hepatic encephalopathy).

Diagnostic Features

The essential feature of catatonic disorder due to another medical condition is the presence

of catatonia that is judged to be attributed to the physiological effects of another medical

condition. Catatonia can be diagnosed by the presence of at least three of the 12 clinical features in Criterion A. There must be evidence from the history, physical examination, or

laboratory findings that the catatonia is attributable to another medical condition (Criterion B). The diagnosis is not given if the catatonia is better explained by another mental

disorder (e.g., manic episode) (Criterion C) or if it occurs exclusively during the course of

a delirium (Criterion D).

Associated Features Supporting Diagnosis

A variety of medical conditions may cause catatonia, especially neurological conditions

(e.g., neoplasms, head trauma, cerebrovascular disease, encephalitis) and metabolic conditions (e.g., hypercalcemia, hepatic encephalopathy, homocystinuria, diabetic ketoacidosis). The associated physical examination findings, laboratory findings, and patterns of

prevalence and onset reflect those of the etiological medical condition.

Differential Diagnosis

A separate diagnosis of catatonic disorder due to another medical condition is not given if

the catatonia occurs exclusively during the course of a delirium or neuroleptic malignant

syndrome. If the individual is currently taking neuroleptic medication, consideration

should be given to medication-induced movement disorders (e.g., abnormal positioning

may be due to neuroleptic-induced acute dystonia) or neuroleptic malignant syndrome

(e.g., catatonic-like features may be present, along with associated vital sign and/or laboratory abnormalities). Catatonic symptoms may be present in any of the following five

psychotic disorders: brief psychotic disorder, schizophreniform disorder, schizophrenia,

schizoaffective disorder, and substance/medication-induced psychotic disorder. It may

also be present in some of the neurodevelopmental disorders, in all of the bipolar and depressive disorders, and in other mental disorders.

Unspecified Catatonia

This category applies to presentations in which symptoms characteristic of catatonia

cause clinically significant distress or impairment in social, occupational, or other important areas of functioning but either the nature of the underlying mental disorder or other

medical condition is unclear, full criteria for catatonia are not met, or there is insufficient

information to make a more specific diagnosis (e.g., in emergency room settings).

Coding note: Code first 781.99 (R29.818) other symptoms involving nervous and musculoskeletal systems, followed by 293.89 (F06.1) unspecified catatonia.

Other Specified Schizophrenia Spectrum and

Other Psychotic Disorder

298.8 (F28)

This category applies to presentations in which symptoms characteristic of a schizophrenia spectrum and other psychotic 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 schizophrenia spectrum and other

psychotic disorders diagnostic class. The other specified schizophrenia spectrum and other psychotic disorder category is used in situations in which the clinician chooses to communicate the specific reason that the presentation does not meet the criteria for any

specific schizophrenia spectrum and other psychotic disorder. This is done by recording “other specified schizophrenia spectrum and other psychotic disorder” followed by the specific

reason (e.g., “persistent auditory hallucinations”).

Examples of presentations that can be specified using the “other specified” designation

include the following:

1. Persistent auditory liallucinations occurring in the absence of any other features.

2. Deiusions with significant overlapping mood episodes: This includes persistent

delusions with periods of overlapping mood episodes that are present for a substantial

portion of the delusional disturbance (such that the criterion stipulating only brief mood

disturbance in delusional disorder is not met).

3. Attenuated psychiosis syndrome: This syndrome is characterized by psychotic-like

symptoms that are below a threshold for full psychosis (e.g., the symptoms are less

severe and more transient, and insight is relatively maintained).

4. Deiusionai symptoms in partner of individuai witii deiusionai disorder: In the

context of a relationship, the delusional material from the dominant partner provides

content for delusional belief by the individual who may not othenwise entirely meet criteria for delusional disorder.

Unspecified Schizophrenia Spectrum and

Other Psychotic Disorder

298.9 (F29)

This category applies to presentations in which symptoms characteristic of a schizophrenia spectrum and other psychotic 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 schizophrenia spectrum and other psychotic disorders diagnostic class. The unspecified schizophrenia spectrum and other psychotic disorder category is used in situations in which the clinician chooses not to

specify the reason that the criteria are not met for a specific schizophrenia spectrum and

other psychotic disorder, and includes presentations in which there is insufficient information to make a more specific diagnosis (e.g., in emergency room settings).

^ ~ Bipolar and

Related Disorders

B ip o ls r S n d rG lâ ted disorders are separated from the depressive disorders in

DSM-5 and placed between the chapters on schizophrenia spectrum and other psychotic

disorders and depressive disorders in recognition of their place as a bridge between the

two diagnostic classes in terms of symptomatology, family history, and genetics. The diagnoses included in this chapter are bipolar I disorder, bipolar II disorder, cyclothymic

disorder, substance/medication-induced bipolar and related disorder, bipolar and related disorder due to another medical condition, other specified bipolar and related disorder, and unspecified bipolar and related disorder.

The bipolar I disorder criteria represent the modern understanding of the classic

manic-depressive disorder or affective psychosis described in the nineteenth century, differing from that classic description only to the extent that neither psychosis nor the lifetime

experience of a major depressive episode is a requirement. However, the vast majority of

individuals whose symptoms meet the criteria for a fully syndromal manic episode also

experience major depressive episodes during the course of their lives.

Bipolar II disorder, requiring the lifetime experience of at least one episode of major depression and at least one hypomanie episode, is no longer thought to be a "milder" condition

than bipolar I disorder, largely because of the amount of time individuals with this condition spend in depression and because the instability of mood experienced by individuals

with bipolar II disorder is typically accompanied by serious impairment in work and social

functioning.

The diagnosis of cyclothymic disorder is given to adults who experience at least 2 years

(for children, a full year) of both hypomanie and depressive periods without ever fulfilling

the criteria for an episode of mania, hypomania, or major depression.

A large number of substances of abuse, some prescribed medications, and several

medical conditions can be associated with manic-like phenomena. This fact is recognized

in the diagnoses of substance/medication-induced bipolar and related disorder and bipolar and related disorder due to another medical condition.

The recognition that many individuals, particularly children and, to a lesser extent, adolescents, experience bipolar-like phenomena that do not meet the criteria for bipolar I, bipolar II, or cyclothymic disorder is reflected in the availability of the other specified

bipolar and related disorder category. Indeed, specific criteria for a disorder involving

short-duration hypomania are provided in Section III in the hope of encouraging further

study of this disorder.

Bipolar I Disorder

Diagnostic Criteria

For a diagnosis of bipolar I disorder, it is necessary to meet tlie following criteria for a manic

episode. The manic episode may have been preceded by and may be followed by hypomanic or major depressive episodes.

Manic Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood

and abnormally and persistently increased goal-directed activity or energy, lasting at

least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

B. During the period of mood disturbance and increased energy or activity, three (or

more) of the following symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external

stimuli), as reported or observed.

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or

psychomotor agitation (i.e., puφoseless non-goal-directed activity).

7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or

foolish business investments).

C. The mood disturbance is sufficiently severe to cause marked impairment in social or

occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

D. The episode is not attributable to the physiological effects of a substance (e.g., a drug

of abuse, a medication, other treatment) or to another medical condition.

Note: A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the

physiological effect of that treatment is sufficient evidence for a manic episode and,

therefore, a bipolar I diagnosis.

Note: Criteria A-D constitute a manic episode. At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.

Hypomanie Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood

and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day.

B. During the period of mood disturbance and increased energy and activity, three (or

more) of the following symptoms (four if the mood is only irritable) have persisted, represent a noticeable change from usual behavior, and have been present to a significant

degree:

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external

stimuli), as reported or observed.

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or

psychomotor agitation.

7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or

foolish business investments).

C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

D. The disturbance in mood and the change in functioning are observable by others.

E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the

episode is, by definition, manic.

F. The episode is not attributable to the physiological effects of a substance (e.g., a drug

of abuse, a medication, other treatment).

Note: A full hypomanie episode that emerges during antidepressant treatment (e.g.,

medication, electroconvulsive therapy) but persists at a fully syndromal level beyond

the physiological effect of that treatment is sufficient evidence for a hypomanie episode

diagnosis. However, caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken

as sufficient for diagnosis of a hypomanie episode, nor necessarily indicative of a bipolar diathesis.

Note: Criteria A-'F constitute a hypomanie episode. Hypomanie episodes are common in

bipolar I disorder but are not required for the diagnosis of bipolar I disorder.

Major Depressive Episode

A. Five (or more) of the following symptoms have been present during the same 2-week

period and represent a change from previous functioning; at least one of the symptoms

is either (1) depressed mood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly attributable to another medical condition.

1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g.,

appears tearful). (Note: In children and adolescents, can be irritable mood.)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the

day, nearly every day (as indicated by either subjective account or observation).

3. Significant weight loss when not dieting or weight gain (e.g., a change of more than

5% of body weight in a month), or decrease or increase in appetite nearly every

day. (Note: In children, consider failure to make expected weight gain.)

4. Insomnia or hypersomnia nearly every day.

5. Psychomotor agitation or retardation nearly every day (observable by others; not

merely subjective feelings of restlessness or being slowed down).

6. Fatigue or loss of energy nearly every day.

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

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

C. The episode is not attributable to the physiological effects of a substance or another

medical condition.

Note: Criteria A-C constitute a major depressive episode. Major depressive episodes are

common in bipolar I disorder but are not required for the diagnosis of bipolar I disorder.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a

natural disaster, a serious medical illness or disability) may include the feelings of intense

sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive

episode in addition to the normal response to a significant loss should also be carefully

considered. This decision inevitably requires the exercise of clinical judgment based on

the individual’s history and the cultural norms for the expression of distress in the context

of loss.^

Bipolar I Disorder

A. Criteria have been met for at least one manic episode (Criteria A-D under “Manic Episode” above).

B. The occurrence of the manic and major depressive episode(s) is not better explained

by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic

disorder.

Coding and Recording Procedures

The diagnostic code for bipolar I disorder is based on type of current or most recent episode and its status with respect to current severity, presence of psychotic features, and

remission status. Current severity and psychotic features are only indicated if full criteria

are currently met for a manic or major depressive episode. Remission specifiers are only

indicated if the full criteria are not currently met for a manic, hypomanie, or major depressive episode. Codes are as follows:

Bipolar 1 disorder

Current or

most recent

episode

manic

Current or

most recent

episode

hypomanie*

Current or

most recent

episode

depressed

Current or

most recent

episode

unspecified**

Mild (p. 154) 296.41 ΝΑ 296.51 NA

(F31.11) (F31.31)

Moderate (p. 154) 296.42 ΝΑ 296.52 NA

(F31.12) (F31.32)

Severe (p. 154) 296.43 ΝΑ 296.53 NA

(F31.13) (F31.4)

^ In distinguishing grief from a major depressive episode (MDE), it is useful to consider that in

grief the predominant affect is feelings of emptiness and loss, while in MDE it is persistent

depressed mood and the inability to anticipate happiness or pleasure. The dysphoria in grief is

likely to decrease in intensity over days to Wfeeks and occurs in waves, the so-called pangs of

grief. These waves tend to be associated with thoughts or reminders of the deceased. The

depressed mood of a MDE is more persistent and not tied to specific thoughts or preoccupations.

The pain of grief may be accompanied by positive emotions and humor that are uncharacteristic

of the pervasive unhappiness and misery characteristic of a major depressive episode. The

thought content associated with grief generally features a preoccupation with thoughts and

memories of the deceased, rather than the self-critical or pessimistic ruminations seen in a MDE.

In grief, self-esteem is generally preserved, whereas in a MDE, feelings of worthlessness and selfloathing are common. If self-derogatory ideation is present in grief, it typically involves perceived failings vis-à-vis the deceased (e.g., not visiting frequently enough, not telling the

deceased how much he or she was loved). If a bereaved individual thinks about death and dying,

such thoughts are generally focused on the deceased and possibly about "joining" the deceased,

whereas in a major depressive episode such thoughts are focused on ending one's own life

because of feeling worthless, undeserving of life, or unable to cope with the pain of depression.

Bipolar 1 disorder

Current or

most recent

episode

manic

Current or

most recent

episode

hypomanie*

Current or

most recent

episode

depressed

Current or

most recent

episode

unspecified**

With psychotic 296.44 ΝΑ 296.54 NA

features*** (F31.2) (F31.5)

(p. 152)

In partial 296.45 296.45 296.55 NA

remission (p. 154) (F31.73) (F31.73) (F31.75)

In full remission 296.46 296.46 296.56 NA

(p. 154) (F31.74) (F31.74) (F31.76)

Unspecified 296.40 296.40 296.50 NA

(F31.9) (F31.9) (F31.9)

Severity and psychotic specifiers do not apply; code 296.40 (F31.0) for cases not in remission.

Severity, psychotic, and remission specifiers do not apply. Code 296.7 (F31.9).

***If psychotic features are present, code the "with psychotic features" specifier irrespective of episode severity.

In recording the name of a diagnosis, terms should be listed in the following order: bipolar

I disorder, type of current or most recent episode, severity/psychotic/remission specifiers,

followed by as many specifiers without codes as apply to the current or most recent episode.

Specify.

With anxious distress (p. 149)

With mixed features (pp. 149-150)

With rapid cycling (pp. 150-151)

With meianchoiic features (p. 151)

With atypicai features (pp. 151-152)

With mood-congruent psychotic features (p. 152)

With mood-incongruent psychotic features (p. 152)

With catatonia (p. 152). Coding note: Use additional code 293.89 (F06.1).

With péripartum onset (pp. 152-153)

With seasonal pattern (pp. 153-154)

Diagnostic Features

The essential feature of a manic episode is a distinct period during which there is an abnormally, persistently elevated, expansive, or irritable mood and persistently increased

activity or energy that is present for most of the day, nearly every day, for a period of at

least 1 week (or any duration if hospitalization is necessary), accompanied by at least three

additional symptoms from Criterion B. If the mood is irritable rather than elevated or expansive, at least four Criterion B symptoms must be present.

Mood in a manic episode is often described as euphoric, excessively cheerful, high, or

"feeling on top of the world." In some cases, the mood is of such a highly infectious quality

that it is easily recognized as excessive and may be characterized by unlimited and haphazard enthusiasm for interpersonal, sexual, or occupational interactions. For example,

the individual may spontaneously start extensive conversations with strangers in public.

Often the predominant mood is irritable rather than elevated, particularly when the individual's wishes are denied or if the individual has been using substances. Rapid shifts in

mood over brief periods of time may occur and are referred to as lability (i.e., the alterna-

tion among euphoria, dysphoria, and irritability). In children, happiness, silliness and

"goofiness" are normal in the context of special occasions; however, if these symptoms are

recurrent, inappropriate to the context, and beyond what is expected for the developmental level of the child, they may meet Criterion A. If the happiness is unusual for a child (i.e.,

distinct from baseline), and the mood change occurs at the same time as symptoms that

meet Criterion B for mania, diagnostic certainty is increased; however, the mood change

must be accompanied by persistently increased activity or energy levels that are obvious

to those who know the child well.

During the manic episode, the individual may engage in multiple overlapping new

projects. The projects are often initiated with little knowledge of the topic, and nothing seems

out of the individual's reach. The increased activity levels may manifest at unusual hours of

the day.

Inflated self-esteem is typically present, ranging from uncritical self-confidence to marked

grandiosity, and may reach delusional proportions (Criterion Bl). Despite lack of any particular experience or talent, the individual may embark on complex tasks such as writing a novel

or seeing publicity for some impractical invention. Grandiose delusions (e.g., of having a

special relationship to a famous person) are common. In children, overestimation of abilities

and belief that, for example, they are the best at a sport or the smartest in the class is normal;

however, when such beliefs are present despite clear evidence to the contrary or the child attempts feats that are clearly dangerous and, most important, represent a change from the

child's normal behavior, the grandiosity criterion should be considered satisfied.

One of the most common features is a decreased need for sleep (Criterion B2) and is

distinct from insomnia in which the individual wants to sleep or feels the need to sleep but

is unable. The individual may sleep httle, if at all, or may awaken several hours earlier than

usual, feeling rested and full of energy. When the sleep disturbance is severe, the individual may go for days without sleep, yet not feel tired. Often a decreased need for sleep heralds the onset of a manic episode.

Speech can be rapid, pressured, loud, and difficult to interrupt (Criterion B3). Individuals may talk continuously and without regard for others' wishes to communicate, often

in an intrusive manner or without concern for the relevance of what is said. Speech is

sometimes characterized by jokes, puns, amusing irrelevancies, and theatricality, with

dramatic mannerisms, singing, and excessive gesturing. Loudness and forcefulness of

speech often become more important than what is conveyed. If the individual's mood is

more irritable than expansive, speech may be marked by complaints, hostile comments, or

angry tirades, particularly if attempts are made to interrupt the individual. Both Criterion

A and Criterion B symptoms may be accompanied by symptoms of the opposite (i.e., depressive) pole (see "with mixed features" specifier, pp. 149-150).

Often the individual's thoughts race at a rate faster than they can be expressed through

speech (Criterion B4). Frequently there is flight of ideas evidenced by a nearly continuous flow

of accelerated speech, with abrupt shifts from one topic to another. When flight of ideas is severe, speech may become disorganized, incoherent, and particularly distressful to the individual. Sometimes thoughts are experienced as so crowded that it is very difficult to speak.

Distractibility (Criterion B5) is evidenced by an inability to censor immaterial external

stimuli (e.g., the interviewer's attire, background noises or conversations, furnishings in

the room) and often prevents individuals experiencing mania from holding a rational conversation or attending to instructions.

The increase in goal-directed activity often consists of excessive planning and participation in multiple activities, including sexual, occupational, political, or religious activities. Increased sexual drive, fantasies, and behavior are often present. Individuals in a manic

episode usually show increased sociability (e.g., renewing old acquaintances or calling or

contacting friends or even strangers), without regard to the intrusive, domineering, and

demanding nature of these interactions. They often display psychomotor agitation or restlessness (i.e., purposeless activity) by pacing or by holding multiple conversations simulta­

neously. Some individuals write excessive letters, e-mails, text messages, and so forth, on

many different topics to friends, public figures, or the media.

The increased activity criterion can be difficult to ascertain in children; however, when

the child takes on many tasks simultaneously, starts devising elaborate and unrealistic

plans for projects, develops previously absent and developmentally inappropriate sexual

preoccupations (not accounted for by sexual abuse or exposure to sexually explicit material), then Criterion B might be met based on clinical judgment. It is essential to determine

whether the behavior represents a change from the child's baseline behavior; occurs most

of the day, nearly every day for the requisite time period; and occurs in temporal association with other symptoms of mania.

The expansive mood, excessive optimism, grandiosity, and poor judgment often lead

to reckless involvement in activities such as spending sprees, giving away possessions,

reckless driving, foolish business investments, and sexual promiscuity that is unusual for

the individual, even though these activities are likely to have catastrophic consequences

(Criterion B7). The individual may purchase many unneeded items without the money to

pay for them and^ in some cases, give them away. Sexual behavior may include infidelity

or indiscriminate sexual encounters with strangers, often disregarding the risk of sexually

transmitted diseases or interpersonal consequences.

The manic episode must result in marked impairment in social or occupational functioning or require hospitalization to prevent harm to self or others (e.g., financial losses, illegal activities, loss of employment, self-injurious behavior). By definition, the presence of

psychotic features during a manic episode also satisfies Criterion C.

Manic symptoms or syndromes that are attributable to the physiological effects of a

drug of abuse (e.g., in the context of cocaine or amphetamine intoxication), the side effects

of medications or treatments (e.g., steroids, L-dopa, antidepressants, stimulants), or another medical condition do not count toward the diagnosis of bipolar I disorder. However,

a fully syndromal manic episode that arises during treatment (e.g., with medications, electroconvulsive therapy, light therapy) or drug use and persists beyond the physiological effect of the inducing agent (i.e., after a medication is fully out of the individual's system or

the effects of electroconvulsive therapy would be expected to have dissipated completely)

is sufficient evidence for a manic episode diagnosis (Criterion D). Caution is indicated so

that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for diagnosis of a manic or hypomanie

episode, nor necessarily an indication of a bipolar disorder diathesis. It is necessary to

meet criteria for a manic episode to make a diagnosis of bipolar I disorder, but it is not required to have hypomanie or major depressive episodes. However, they may precede or

follow a manic episode. Full descriptions of the diagnostic features of a hypomanie episode may be found within the text for bipolar II disorder, and the features of a major depressive episode are described within the text for major depressive disorder.

Associated Features Supporting Diagnosis

E>uring a manic episode, individuals often do not perceive that they are ill or in need of treatment and vehemently resist efforts to be treated. Individuals may change their dress, makeup,

or personal appearance to a more sexually suggestive or flamboyant style. Some perceive a

sharper sense of smell, hearing, or vision. Gambling and antisocial behaviors may accompany

the manic episode. Some individuals may become hostile and physically threatening to others

and, when delusional, may become physically assaultive or suicidal. Catastrophic consequences of a manic episode (e.g., involuntary hospitalization, difficulties with the law, serious

financial difficulties) often result from poor judgment, loss of insight, and hyperactivity.

Mood may shift very rapidly to anger or depression. Depressive symptoms may occur

during a manic episode and, if present, may last moments, hours, or, more rarely, days (see

"with mixed features" specifier, pp. 149-150).

Prevalence

The 12-month prevalence estimate in the continental United States was 0.6% for bipolar I

disorder as defined in DSM-IV. Twelve-month prevalence of bipolar I disorder across 11

countries ranged from 0.0% to 0.6%. The lifetime male-to-female prevalence ratio is approximately 1.1:1.

Development and Course

Mean age at onset of the first manic, hypomanie, or major depressive episode is approximately 18 years for bipolar I disorder. Special considerations are necessary to detect the diagnosis in children. Since children of the same chronological age may be at different

developmental stages, it is difficult to define with precision what is ''normal" or "expected" at any given point. Therefore, each child should be judged according to his or her

own baseline. Onset occurs throughout the life cycle, including first onsets in the 60s or

70s. Onset of manic symptoms (e.g., sexual or social disinhibition) in late mid-life or latelife should prompt consideration of medical conditions (e.g., frontotemporal neurocognitive disorder) and of substance ingestion or withdrawal.

More than 90% of individuals who have a single manic episode go on to have recurrent

mood episodes. Approximately 60% of manic episodes occur immediately before a major

depressive episode. Individuals with bipolar I disorder who have multiple (four or more)

mood episodes (major depressive, manic, or hypomanie) within 1 year receive the specifier "with rapid cycling."

Risk and Prognostic Factors

Environmental. Bipolar disorder is more common in high-income than in low-income

countries (1.4 vs. 0.7%). Separated, divorced, or widowed individuals have higher rates of

bipolar I disorder than do individuals who are married or have never been married, but

the direction of the association is unclear.

Genetic and physiological. A family history of bipolar disorder is one of the strongest and

most consistent risk factors for bipolar disorders. There is an average 10-fold increased risk

among adult relatives of individuals with bipolar I and bipolar II disorders. Magnitude of

risk increases with degree of kinship. Schizophrenia and bipolar disorder likely share a genetic origin, reflected in familial co-aggregation of schizophrenia and bipolar disorder.

Course modifiers. After an individual has a manic episode with psychotic features, subsequent manic episodes are more likely to include psychotic features. Incomplete interepisode recovery is more common when the current episode is accompanied by moodincongruent psychotic features.

Culture-Related Diagnostic Issues

Little information exists on specific cultural differences in the expression of bipolar I disorder. One possible explanation for this may be that diagnostic instruments are often

translated and applied in different cultures with no transcultural validation. In one U.S.

study, 12-month prevalence of bipolar I disorder was significantly lower for Afro-Caribbeans than for African Americans or whites.

Gender-Related Diagnostic Issues

Females are more likely to experience rapid cycling and mixed states, and to have patterns of

comorbidity that differ from those of males, including higher rates of lifetime eating disorders. Females with bipolar I or II disorder are more likely to experience depressive symptoms

than males. They also have a higher lifetime risk of alcohol use disorder than are males and a

much greater likelihood of alcohol use disorder than do females in the general population.

Suicide Risk

The lifetime risk of suicide in individuals with bipolar disorder is estimated to be at least

15 times that of the general population. In fact, bipolar disorder may account for one-quarter of all completed suicides. A past history of suicide attempt and percent days spent depressed in the past year are associated with greater risk of suicide attempts or completions.

Functional Consequences of Bipoiar I Disorder

Although many individuals with bipolar disorder return to a fully functional level between episodes, approximately 30% show severe impairment in work role function. Functional recovery lags substantially behind recovery from symptoms, especially with respect

to occupational recovery, resulting in lower socioeconomic status despite equivalent levels of education when compared with the general population. Individuals with bipolar I

disorder perform more poorly than healthy individuals on cognitive tests. Cognitive impairments may contribute to vocational and interpersonal difficulties and persist through

the lifespan, evex^ during euthymie periods.

Differential Diagnosis

Major depressive disorder. Major depressive disorder may also be accompanied by hypomanie or manic symptoms (i.e., fewer symptoms or for a shorter duration than required

for mania or hypomania). When the individual presents in an episode of major depression,

one must depend on corroborating history regarding past episodes of mania or hypomania. Symptoms of irritability may be associated with either major depressive disorder or

bipolar disorder, adding to diagnostic complexity.

Other bipolar disorders. Diagnosis of bipolar I disorder is differentiated from bipolar II

disorder by determining whether there have been any past episodes of mania. Other specified and unspecified bipolar and related disorders should be differentiated from bipolar I

and II disorders by considering whether either the episodes involving manic or hypomanic symptoms or the episodes of depressive symptoms fail to meet the full criteria for

those conditions.

Bipolar disorder due to another medical condition may be distinguished from bipolar

I and II disorders by identifying, based on best clinical evidence, a causally related medical

condition.

Generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or other

anxiety disorders. These disorders need to be considered in the differential diagnosis as

either the primary disorder or, in some cases, a comorbid disorder. A careful history of

symptoms is needed to differentiate generalized anxiety disorder from bipolar disorder,

as anxious ruminations may be mistaken for racing thoughts, and efforts to minimize anxious feelings may be taken as impulsive behavior. Similarly, symptoms of posttraumatic

stress disorder need to be differentiated from bipolar disorder. It is helpful to assess the episodic nature of the symptoms described, as well as to consider symptom triggers, in making this differential diagnosis.

Substance/medication-induced bipolar disorder. Substance use disorders may manifest with substance.medication-induced manic symptoms that must be distinguished

from bipolar I disorder; response to mood stabilizers during a substance/medicationinduced mania may not necessarily be diagnostic for bipolar disorder. There may be substantial overlap in view of the tendency for individuals with bipolar I disorder to overuse

substances during an episode. A primary diagnosis of bipolar disorder must be established based on symptoms that remain once substances are no longer being used.

Attention-deficit/hyperactivity disorder. This disorder may be misdiagnosed as bipolar

disorder, especially in adolescents and children. Many symptoms overlap with the symp­

toms of mania, such as rapid speech, racing thoughts, distractibihty, and less need for

sleep. The "double counting" of symptoms toward both ADHD and bipolar disorder can

be avoided if the clinician clarifies whether the symptom(s) represents a distinct episode.

Personality disorders. Personality disorders such as borderline personality disorder

may have substantial symptomatic overlap with bipolar disorders, since mood lability

and impulsivity are common in both conditions. Symptoms must represent a distinct episode, and the noticeable increase over baseline required for the diagnosis of bipolar disorder must be present. A diagnosis of a personality disorder should not be made during an

untreated mood episode.

Disorders with prominent irritability. In individuals with severe irritability, particularly

children and adolescents, care must be taken to apply the diagnosis of bipolar disorder

only to those who have had a clear episode of mania or hypomania—that is, a distinct time

period, of the required duration, during which the irritability was clearly different from

the individual's baseline and was accompanied by the onset of Criterion B symptoms.

When a child's irritability is persistent and particularly severe, the diagnosis of disruptive

mood dysregulation disorder would be more appropriate. Indeed, when any child is being

assessed for mania, it is essential that the symptoms represent a clear change from the

child's typical behavior.

Comorbidity

Co-occurring mental disorders are common, with the most frequent disorders being any

anxiety disorder (e.g., panic attacks, social anxiety disorder [social phobia], specific phobia), occurring in approximately three-fourths of individuals; ADHD, any disruptive, impulse-control, or conduct disorder (e.g., intermittent explosive disorder, oppositional

defiant disorder, conduct disorder), and any substance use disorder (e.g., alcohol use disorder) occur in over half of individuals with bipolar I disorder. Adults with bipolar I disorder have high rates of serious and/or untreated co-occurring medical conditions.

Metabolic s)nidrome and migraine are more common among individuals with bipolar disorder than in the general population. More than half of individuals whose symptoms meet

criteria for bipolar disorder have an alcohol use disorder, and those with both disorders

are at greater risk for suicide attempt.

Bipolar II Disorder

Diagnostic Criteria 296.89 (F31.81)

For a diagnosis of bipolar II disorder, it is necessary to meet the following criteria for a current or past hypomanie episode and the following criteria for a current or past major depressive episode:

Hypomanie Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood

and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day.

B. During the period of mood disturbance and increased energy and activity, three (or more)

of the following symptoms have persisted (four if the mood is only irritable), represent a noticeable change from usual behavior, and have been present to a significant degree:

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external

stimuli), as reported or obsen/ed.

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or

psychomotor agitation.

7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or

foolish business investments).

C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

D. The disturbance in mood and the change in functioning are observable by others.

E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the

episode is, by definition, manic.

F. The episode is not attributable to the physiological effects of a substance (e.g., a drug

of abuse, a medication or other treatment).

Note: A full hypomanie episode that emerges during antidepressant treatment (e.g.,

medication, electroconvulsive therapy) but persists at a fully syndromal level beyond

the physiological effect of that treatment is sufficient evidence for a hypomanie episode

diagnosis. However, caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken

as sufficient for diagnosis of a hypomanie episode, nor necessarily indicative of a bipolar diathesis.

Major Depressive Episode

A. Five (or more) of the following symptoms have been present during the same 2-week

period and represent a change from previous functioning; at least one of the symptoms

is either (1 ) depressed mood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly attributable to a medical condition.

1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g.,

appears tearful). (Note: In children and adolescents, can be irritable mood.)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the

day, nearly every day (as indicated by either subjective account or observation).

3. Significant weight loss when not dieting or weight gain (e.g., a change of more than

5% of body weight in a month), or decrease or increase in appetite nearly every

day. (Note: In children, consider failure to make expected weight gain.)

4. Insomnia or hypersomnia nearly every day.

5. Psychomotor agitation or retardation nearly every day (observable by others; not

merely subjective feelings of restlessness or being slowed down).

6. Fatigue or loss of energy nearly every day.

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for committing suicide.

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

C. The episode is not attributable to the physiological effects of a substance or another

medical condition.

Note: Criteria A-C above constitute a major depressive episode.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion

A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode

in addition to the normal response to a significant loss should be carefully considered. This

decision inevitably requires the exercise of clinical judgment based on the individual’s history

and the cultural norms for the expression of distress in the context of loss.^

Bipolar II Disorder

A. Criteria have been met for at least one hypomanie episode (Criteria A-F under “Hypomanic Episode” above) and at least one major depressive episode (Criteria A-C under

“Major Depressive Episode” above).

B. There has never been a manic episode.

C. The occurrence of the hypomanie episode(s) and major depressive episode(s) is not

better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and

other psychotic disorder.

D. The symptoms of depression or the unpredictability caused by frequent alternation between periods of depression and hypomania causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Coding and Recording Procedures

Bipolar II disorder has one diagnostic code: 296.89 (F31.81 ). Its status with respect to current severity, presence of psychotic features, course, and other specifiers cannot be

coded but should be indicated in writing (e.g., 296.89 [F31.81] bipolar II disorder, current

episode depressed, moderate severity, with mixed features; 296.89 [F31.81] bipolar II disorder, most recent episode depressed, in partial remission).

Specify current or most recent episode:

Hypomanie

Depressed

Specify if:

With anxious distress (p. 149)

With mixed features (pp. 149-150)

^ In distinguishing grief from a major depressive episode (MDE), it is useful to consider that in grief

the predominant affect is feelings of emptiness and loss, while in a MDE it is persistent depressed

mood and the inability to anticipate happiness or pleasure. The dysphoria in grief is likely to

decrease in intensity over days to weeks and occurs in waves, the so-called pangs of grief. These

waves tend to be associated with thoughts or reminders of the deceased. The depressed mood of a

MDE is more persistent and not tied to specific thoughts or preoccupations. The pain of grief may

be accompanied by positive emotions and humor that are uncharacteristic of the pervasive unhappiness and misery characteristic of a MDE. The thought content associated with grief generally features a preoccupation with thoughts and memories of the deceased, rather than the self-critical or

pessinüstic ruminations seen in a MDE. In grief, self-esteem is generally preserved, whereas in a

MDE feelings of worthlessness and self-loathing are common. If self-derogatory ideation is present

in grief, it typically involves perceived failings vis-à-vis the deceased (e.g., not visiting frequently

enough, not telling the deceased how much he or she was loved). If a bereaved individual thinks

about death and dying, such thoughts are generally focused on the deceased and possibly about

"’joining" the deceased, whereas in a MDE such thoughts are focused on ending one's own life

because of feeling worthless, undeserving of üfe, or unable to cope with the pain of depression.

With rapid cycling (pp. 150-151)

Withi mood-congruent psychotic features (p. 152)

With mood-incongruent psychotic features (p. 152)

With catatonia (p. 152). Coding note: Use additional code 293.89 (F06.1).

With péripartum onset (pp. 152-153)

With seasonal pattern (pp. 153-154): Applies only to the pattern of major depressive

episodes.

Specify course if full criteria for a mood episode are not currently met:

in partial remission (p. 154)

In full remission (p. 154)

Specify severity if full criteria for a mood episode are currently met:

lUlild (p. 154)

lUloderate (p. 154)

Severe (p. 154)_______________________________________________________

Diagnostic Features

Bipolar II disorder is characterized by a clinical course of recurring mood episodes consisting of one or more major depressive episodes (Criteria A-C under "Major Depressive

Episode") and at least one hypomanie episode (Criteria A-F under "Hypomanie Episode"). The major depressive episode must last at least 2 weeks, and the hypomarüc episode must last at least 4 days, to meet the diagnostic criteria. During the mood episode(s),

the requisite number of symptoms must be present most of the day, nearly every day, and

represent a noticeable change from usual behavior and functioning. The presence of a

manic episode during the course of illness precludes the diagnosis of bipolar II disorder

(Criterion B under "Bipolar II Disorder"). Episodes of substance/medication-induced depressive disorder or substance/medication-induced bipolar and related disorder (representing the physiological effects of a medication, other somatic treatments for depression,

drugs of abuse, or toxin exposure) or of depressive and related disorder due to another

medical condition or bipolar and related disorder due to another medical condition do not

count toward a diagnosis of bipolar II disorder unless they persist beyond the physiological effects of the treatment or substance and then meet duration criteria for an episode. In

addition, the episodes must not be better accounted for by schizoaffective disorder and are

not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or

other specified or unspecified schizophrenia spectrum or other psychotic disorders (Criterion C under "Bipolar II Disorder"). The depressive episodes or hypomanie fluctuations

must cause clinically significant distress or impairment in social, occupational, or other

important areas of functioning (Criterion D under "Bipolar II Disorder"); however, for hypomanie episodes, this requirement does not have to be met. A hypomanie episode that

causes significant impairment would likely qualify for the diagnosis of manic episode and,

therefore, for a lifetime diagnosis of bipolar I disorder. The recurrent major depressive episodes are often more frequent and lengthier than those occurring in bipolar I disorder.

Individuals with bipolar II disorder typically present to a clinician during a major depressive episode and are unlikely to complain initially of hypomania. Typically, the hypomanie episodes themselves do not cause impairment. Instead, the impairment results

from the major depressive episodes or from a persistent pattern of unpredictable mood

changes and fluctuating, unreliable interpersonal or occupational functioning. Individuals with bipolar II disorder may not view the hypomanie episodes as pathological or disadvantageous, although others may be troubled by the individual's erratic behavior.

Clinical information from other informants, such as close friends or relatives, is often useful in establishing the diagnosis of bipolar II disorder.

A hypomanie episode should not be confused with the several days of euthymia and restored energy or activity that may follow remission of a major depressive episode. Despite the

substantial differences in duration and severity between a manic and hypomanie episode, bipolar II disorder is not a "milder form" of bipolar I disorder. Compared with individuals with

bipolar I disorder, individuals with bipolar II disorder have greater chronicity of illness and

spend, on average, more time in the depressive phase of their illness, which can be severe and/

or disabling. Depressive symptoms co-occurring with a hypomanie episode or hypomanie

symptoms co-occurring with a depressive episode are common in individuals with bipolar Π

disorder and are overrepresented in females, particularly hypomania with mixed features. Individuals experiencing hypomania with mixed features may not label their symptoms as hypomania, but instead experience them as depression with increased energy or irritability.

Associated Features Supporting Diagnosis

A common feature of bipolar II disorder is impulsivity, which can contribute to suicide attempts and substance use disorders. Impulsivity may also stem from a concurrent personality disorder, substance use disorder, anxiety disorder, another mental disorder, or a

medical condition. There may be heightened levels of creativity in some individuals with

a bipolar disorder. However, that relationship may be nonlinear; that is, greater lifetime

creative accomplishments have been associated with milder forms of bipolar disorder, and

higher creativity has been found in unaffected family members. The individual's attachment to heightened creativity during hypomanie episodes may contribute to ambivalence

about seeking treatment or undermine adherence to treatment.

Prevaience

The 12-month prevalence of bipolar II disorder, internationally, is 0.3%. In the United

States, 12-month prevalence is 0.8%. The prevalence rate of pediatric bipolar II disorder is

difficult to establish. DSM-IV bipolar I, bipolar II, and bipolar disorder not otherwise specified yield a combined prevalence rate of 1.8% in U.S. and non-U.S. community samples,

with higher rates (2.7% inclusive) in youths age 12 years or older.

Deveiopment and Course

Although bipolar II disorder can begin in late adolescence and throughout adulthood, average age at onset is the mid-20s, which is slightly later than for bipolar I disorder but earlier than for major depressive disorder. The illness most often begins with a depressive

episode and is not recognized as bipolar II disorder until a hypomanie episode occurs; this

happens in about 12% of individuals with the initial diagnosis of major depressive disorder. Anxiety, substance use, or eating disorders may also precede the diagnosis, complicating its detection. Many individuals experience several episodes of major depression

prior to the first recognized hypomanie episode.

The number of lifetime episodes (both hypomanie and major depressive episodes)

tends to be higher for bipolar II disorder than for major depressive disorder or bipolar I

disorder. However, individuals with bipolar I disorder are actually more likely to experience hypomanie symptoms than are individuals with bipolar II disorder.The interval

between mood episodes in the course of bipolar II disorder tends to decrease as the individual ages. While the hypomanie episode is the feature that defines bipolar II disorder,

depressive episodes are more enduring and disabling over time. Despite the predominance of depression, once a hypomanie episode has occurred, the diagnosis becomes bipolar II disorder and never reverts to major depressive disorder.

Approximately 5%-15% of individuals with bipolar II disorder have multiple (four or

more) mood episodes (hypomanie or major depressive) within the previous 12 months. If

this pattern is present, it is noted by the specifier "with rapid cycling." By definition, psychotic symptoms do not occur in hypomanie episodes, and they appear to be less frequent

in the major depressive episodes in bipolar II disorder than in those of bipolar I disorder.

Switching from a depressive episode to a manic or hypomanie episode (with or without mixed features) may occur, both spontaneously and during treatment for depression.

About 5%-15% of individuals with bipolar II disorder will ultimately develop a manic episode, which changes the diagnosis to bipolar I disorder, regardless of subsequent course.

Making the diagnosis in children is often a challenge, especially in those with irritability and hyperarousal that is nonepisodic (i.e., lacks the well-demarcated periods of altered

mood). Nonepisodic irritability in youth is associated with an elevated risk for anxiety disorders and major depressive disorder, but not bipolar disorder, in adulthood. Persistently

irritable youths have lower familial rates of bipolar disorder than do youths who have bipolar disorder. For a hypomanie episode to be diagnosed, the child's symptoms must exceed what is expected in a given environment and culture for the child's developmental

stage. Compared with adult onset of bipolar II disorder, childhood or adolescent onset of

the disorder may be associated with a more severe lifetime course. The 3-year incidence

rate of first-onset bipolar II disorder in adults older than 60 years is 0.34%. However, distinguishing individuals older than 60 years with bipolar II disorder by late versus early

age at onset does not appear to have any clinical utility.

Risk and Prognostic Factors

Genetic and physiological. The risk of bipolar II disorder tends to be highest among relatives of individuals with bipolar II disorder, as opposed to individuals with bipolar I disorder or major depressive disorder. There may be genetic factors influencing the age at

onset for bipolar disorders.

Course modifiers. A rapid-cycling pattern is associated with a poorer prognosis. Return

to previous level of social function for individuals with bipolar II disorder is more likely

for individuals of younger age and with less severe depression, suggesting adverse effects

of prolonged illness on recovery. More education, fewer years of illness, and being married are independently associated with functional recovery in individuals with bipolar

disorder, even after diagnostic type (I vs. II), current depressive symptoms, and presence

of psychiatric comorbidity are taken into account.

Gender-Reiated Diagnostic issues

Whereas the gender ratio for bipolar I disorder is equal, findings on gender differences in

bipolar II disorder are mixed, differing by type of sample (i.e., registry, community, or

clinical) and country of origin. There is little to no evidence of bipolar gender differences,

whereas some, but not all, clinical samples suggest that bipolar II disorder is more common in females than in males, which may reflect gender differences in treatment seeking

or other factors.

Patterns of illness and comorbidity, however, seem to differ by gender, with females

being more likely than males to report hypomania with mixed depressive features and a

rapid-cycling course. Childbirth may be a specific trigger for a hypomanie episode, which

can occur in 10%-20% of females in nonelinieal populations and most typically in the early

postpartum period. Distinguishing hypomania from the elated mood and reduced sleep

that normally accompany the birth of a child may be challenging. Postpartum hypomania

may foreshadow the onset of a depression that occurs in about half of females who experience postpartum "highs." Accurate detection of bipolar II disorder may help in establishing appropriate treatment of the depression, which may reduce the risk of suicide and

infanticide.

Suicide Risk

Suicide risk is high in bipolar II disorder. Approximately one-third of individuals with bipolar II disorder report a lifetime history of suicide attempt. The prevalence rates of lifetime attempted suicide in bipolar II and bipolar I disorder appear to be similar (32.4% and

36.3%, respectively). However, the lethality of attempts, as defined by a lower ratio of attempts to completed suicides, may be higher in individuals with bipolar II disorder compared with individuals with bipolar I disorder. There may be an association between

genetic markers and increased risk for suicidal behavior in individuals with bipolar disorder, including a 6.5-fold higher risk of suicide among first-degree relatives of bipolar II

probands compared with those with bipolar I disorder.

Functional Consequences of Bipolar II Disorder

Although many individuals with bipolar II disorder return to a fully functional level between mood episodes, at least 15% continue to have some inter-episode dysfunction, and

20% transition directly into another mood episode without inter-episode recovery. Functional recovery lags substantially behind recovery from symptoms of bipolar II disorder,

especially in regard to occupational recovery, resulting in lower socioeconomic status despite equivalent levels of education with the general population. Individuals with bipolar

II disorder perform more poorly than healthy individuals on cognitive tests and, with the

exception of memory and semantic fluency, have similar cognitive impairment as do individuals with bipolar I disorder. Cognitive impairments associated with bipolar II disorder may contribute to vocational difficulties. Prolonged unemployment in individuals

with bipolar disorder is associated with more episodes of depression, older age, increased

rates of current panic disorder, and lifetime history of alcohol use disorder.

Differential Diagnosis

Major depressive disorder. Perhaps the most challenging differential diagnosis to consider is major depressive disorder, which may be accompanied by hypomanie or manic

symptoms that do not meet full criteria (i.e., either fewer symptoms or a shorter duration

than required for a hypomanie episode). This is especially true in evaluating individuals

with symptoms of irritability, which may be associated with either major depressive disorder or bipolar II disorder.

Cyclothymic disorder. In cyclothymic disorder, there are numerous periods of hypomanic symptoms and numerous periods of depressive symptoms that do not meet symptom or duration criteria for a major depressive episode. Bipolar II disorder is distinguished

from cyclothymic disorder by the presence of one or more major depressive episodes. If a

major depressive episode occurs after the first 2 years of cyclothymic disorder, the additional diagnosis of bipolar II disorder is given.

Schizophrenia spectrum and other related psychotic disorders. Bipolar II disorder must

be distinguished from psychotic disorders (e.g., schizoaffective disorder, schizophrenia,

and delusional disorder). Schizophrenia, schizoaffective disorder, and delusional disorder are all characterized by periods of psychotic symptoms that occur in the absence of

prominent mood symptoms. Other helpful considerations include the accompanying

symptoms, previous course, and family history.

Panic disorder or other anxiety disorders. Anxiety disorders need to be considered in

the differential diagnosis and may frequently be present as co-occurring disorders.

Substance use disorders. Substance use disorders are included in the differential diagnosis.

Attention-deficit/hyperactivity disorder. Attention-deficit/hyperactivity disorder (ADHD)

may be misdiagnosed as bipolar II disorder, especially in adolescents and children. Many

symptoms of ADHD, such as rapid speech, racing thoughts, distractibility, and less need

for sleep, overlap with the symptoms of hypomania. The double counting of symptoms toward both ADHD and bipolar II disorder can be avoided if the clinician clarifies whether

the symptoms represent a distinct episode and if the noticeable increase over baseline required for the diagnosis of bipolar II disorder is present.

Personality disorders. The same convention as applies for ADHD also applies when

evaluating an individual for a personality disorder such as borderline personality disorder, since mood lability and impulsivity are common in both personality disorders and bipolar II disorder. Symptoms must represent a distinct episode, and the noticeable increase

over baseline required for the diagnosis of bipolar II disorder must be present. A diagnosis

of a personality disorder should not be made during an untreated mood episode unless

the lifetime history supports the presence of a personality disorder.

Other bipolar disorders. Diagnosis of bipolar II disorder should be differentiated from

bipolar I disorder by carefully considering whether there have been any past episodes of

mania and from other specified and unspecified bipolar and related disorders by confirming the presence of fully syndromal hypomania and depression.

Comorbidity

Bipolar II disorder is more often than not associated with one or more co-occurring mental

disorders, with anxiety disorders being the most common. Approximately 60% of individuals with bipolar II disorder have three or more co-occurring mental disorders; 75% have

an anxiety disorder; and 37% have a substance use disorder. Children and adolescents

with bipolar II disorder have a higher rate of co-occurring anxiety disorders compared

with those with bipolar I disorder, and the anxiety disorder most often predates the bipolar disorder. Anxiety and substance use disorders occur in individuals with bipolar II

disorder at a higher rate than in the general population. Approximately 14% of individuals

with bipolar II disorder have at least one lifetime eating disorder, with binge-eating disorder being more common than bulimia nervosa and anorexia nervosa.

These commonly co-occurring disorders do not seem to follow a course of illness that

is truly independent from that of the bipolar disorder, but rather have strong associations

with mood states. For example, anxiety and eating disorders tend to associate most with

depressive symptoms, and substance use disorders are moderately associated with manic

symptoms.

Cyclothymic Disorder

Diagnostic Criteria 301.13 (F34.0)

A. For at least 2 years (at least 1 year in children and adolescents) there have been numerous periods with hypomanie symptoms that do not meet criteria for a hypomanie

episode and numerous periods with depressive symptoms that do not meet criteria for

a major depressive episode.

B. During the above 2-year period (1 year in children and adolescents), the hypomanie

and depressive periods have been present for at least half the time and the individual

has not been without the symptoms for more than 2 months at a time.

C. Criteria for a major depressive, manic, or hypomanie episode have never been met.

D. The symptoms in Criterion A are not better explained by schizoaffective disorder,

schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

E. The symptoms are not attributable to the physiological effects of a substance (e.g., a

drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism).

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

Specify if:

With anxious distress (see p. 149)_______________________________________

Diagnostic Features

The essential feature of cyclothymic disorder is a chronic, fluctuating mood disturbance

involving numerous periods of hypomanie symptoms and periods of depressive symptoms that are distinct from each other (Criterion A). The hypomanie symptoms are of

insufficient number, severity, pervasiveness, or duration to meet full criteria for a hypomanic episode, and the depressive symptoms are of insufficient number, severity, pervasiveness, or duration to meet full criteria for a major depressive episode. During the initial

2-year period (1 year for children or adolescents), the symptoms must be persistent (present more days than not), and any symptom-free intervals last no longer than 2 months

(Criterion B). The diagnosis of cyclothymic disorder is made only if the criteria for a major

depressive, manic, or hypomanie episode have never been met (Criterion C).

If an individual with cyclothymic disorder subsequently (i.e., after the initial 2 years in

adults or 1 year in children or adolescents) experiences a major depressive, manic, or hypomanie episode, the diagnosis changes to major depressive disorder, bipolar I disorder,

or other specified or unspecified bipolar and related disorder (subclassified as hypomanie

episode without prior major depressive episode), respectively, and the cyclothymic disorder diagnosis is dropped.

The cyclothymic disorder diagnosis is not made if the pattern of mood swings is better

explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other

psychotic disorders (Criterion D), in which ease the mood symptoms are considered associated features of the psychotic disorder. The mood disturbance must also not be attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or

another medical condition (e.g., hyperthyroidism) (Criterion E). Although some individuals may function particularly well during some of the periods of hypomania, over the

prolonged course of the disorder, there must be clinically significant distress or impairment in social, occupational, or other important areas of functioning as a result of the

mood disturbance (Criterion F). The impairment may develop as a result of prolonged periods of cyclical, often unpredictable mood changes (e.g., the individual may be regarded

as temperamental, moody, unpredictable, inconsistent, or unreliable).

Prevaience

The lifetime prevalence of cyclothymic disorder is approximately 0.4%-l%. Prevalence in

mood disorders clinics may range from 3% to 5%. In the general population, cyclothymic

disorder is apparently equally common in males and females. In clinical settings, females

with cyclothymic disorder may be more likely to present for treatment than males.

Deveiopment and Course

Cyclothymic disorder usually begins in adolescence or early adult life and is sometimes

considered to reflect a temperamental predisposition to other disorders in this chapter.

Cyclothymic disorder usually has an insidious onset and a persistent course. There is a

15%-50% risk that an individual with cyclothymic disorder will subsequently develop bipolar I disorder or bipolar II disorder. Onset of persistent, fluctuating hypomanie and depressive symptoms late in adult life needs to be clearly differentiated from bipolar and

related disorder due to another medical condition and depressive disorder due to another

medical condition (e.g., multiple sclerosis) before the cyclothymic disorder diagnosis is assigned. Among children with cyclothymic disorder, the mean age at onset of symptoms is

6.5 years of age.

Risk and Prognostic Factors

Genetic and physiological. Major depressive disorder, bipolar I disorder, and bipolar II

disorder are more common among first-degree biological relatives of individuals with cyclothymic disorder than in the general population. There may also be an increased familial risk of

substance-related disorders. Cyclotiiymic disorder may be more common in the first-degree

biological relatives of individuals witiK bipolar I disorder than in the general population.

Differentiai Diagnosis

Bipolar and related disorder due to another medical condition and depressive disorder

due to another medical condition. The diagnosis of bipolar and related disorder due to

another medical condition or depressive disorder due to another medical condition is

made when the mood disturbance is judged to be attributable to the physiological effect of

a specific, usually chronic medical condition (e.g., hyperthyroidism). This determination

is based on the history, physical examination, or laboratory findings. If it is judged that the

hypomanie and depressive symptoms are not the physiological consequence of the medical condition, then the primary mental disorder (i.e., cyclothymic disorder) and the medical condition are coded. For example, this would be the case if the mood symptoms are

considered to be the psychological (not the physiological) consequence of having a chronic

medical condition, or if there is no etiological relationship between the hypomanie and depressive symptoms and the medical condition.

Substance/medication-induced bipolar and related disorder and substance/medication-induced depressive disorder. Substance/medication-induced bipolar and related

disorder and substance/medication-induced depressive disorder are distinguished from

cyclothymic disorder by the judgment that a substance/medication (especially stimulants) is etiologically related to the mood disturbance. The frequent mood swings in these

disorders that are suggestive of cyclothymic disorder usually resolve following cessation

of substance/medication use.

Bipolar I disorder, with rapid cycling, and bipolar II disorder, with rapid cycling.

Both disorders may resemble cyclothymic disorder by virtue of the frequent marked shifts

in mood. By definition, in cyclothymic disorder the criteria for a major depressive, manic,

or hypomanie episode has never been met, whereas the bipolar I disorder and bipolar II

disorder specifier "with rapid cycling" requires that full mood episodes be present.

Borderline personality disorder. Borderline personality disorder is associated with

marked shifts in mood that may suggest cyclothymic disorder. If the criteria are met for

both disorders, both borderline personality disorder and cyclothymic disorder may be diagnosed.

Comorbidity

Substance-related disorders and sleep disorders (i.e., difficulties in initiating and maintaining sleep) may be present in individuals with cyclothymic disorder. Most children

with cyclothymic disorder treated in outpatient psychiatric settings have comorbid mental

conditions; they are more likely than other pediatric patients with mental disorders to

have comorbid attention-deficit/hyperactivity disorder.

Substance/Medication-Induced

Bipolar and Related Disorder

Diagnostic Criteria

A. A prominent and persistent disturbance in mood that predominates in the clinical picture

and is characterized by elevated, expansive, or irritable mood, with or without depressed

mood, or markedly diminished interest or pleasure in all, or almost all, activities.

B. There is evidence from the history, physical examination, or laboratory findings of both

(1)and (2):

1. The symptoms in Criterion A developed during or soon after substance intoxication

or withdrawal or after exposure to a medication.

2. The involved substance/medication is capable of producing the symptoms in Criterion A.

C. The disturbance is not better explained by a bipolar or related disorder that is not substance/medication-induced. Such evidence of an independent bipolar or related disorder could include the following:

The symptoms precede the onset of the substance/medication use; the symptoms persist for a substantial period of time (e.g., about 1 month) after the cessation of acute

withdrawal or severe intoxication; or there is other evidence suggesting the existence

of an independent non-substance/medication-induced bipolar and related disorder

(e.g., a history of recurrent non-substance/medication-related episodes).

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Coding note: The ICD-9-CM and ICD-10-CM codes for the [specific substance/medication]-

induced bipolar and related disorders 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 substanceinduced bipolar and related disorder, the 4th position character is “1,” and the clinician should

record “mild [substance] use disorder'’ before the substance-induced bipolar and related disorder (e.g., “mild cocaine use disorder with cocaine-induced bipolar and related disorder”). If a

moderate or severe substance use disorder is comorbid with the substance-induced bipolar

and related 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 (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-induced bipolar and related disorder.

ICD-10-CM

With use

disorder,

ICD-9-CIVI mild

With use

disorder,

moderate

or severe

Without

use

disorder

Alcohol

Phencyclidine

Other hallucinogen

291.89

292.84

292.84

F10.14

F16.14

F16.14

F10.24

FI 6.24

FI 6.24

FI 0.94

F16.94

F16.94

ICD-10-CM

ICD-9-CM

With use

disorder,

mild

With use

disorder,

moderate

or severe

Without

use

disorder

Sedative, hypnotic, or anxiolytic 292.84 F13.14 F13.24 F13.94

Amphetamine (or other

stimulant)

292.84 F15.14 F15.24 FI 5.94

Cocaine 292.84 F14.14 F14.24 F14.94

Other (or unknown) substance 292.84 F19.14 F19.24 FI 9.94

Specify if (see Table 1 in the chapter “Substance-Related and Addictive Disorders” for diagnoses associated with substance class):

With onset during intoxication: If the criteria are met for intoxication with the substance and the symptoms develop during intoxication.

With onset during withdrawal: If criteria are met for withdrawal from the substance

and the symptoms develop during, or shortly after, withdrawal.

Recording Procedures

ICD-9-CM. The name of the substance/medication-induced bipolar and related disorder begins with the specific substance (e.g., cocaine, dexamethasone) that is presumed to

be causing the bipolar mood 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 (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 specification of onset (i.e., onset during intoxication, onset during withdrawal). Unlike the recording procedures for ICD-IO-CM,

which combine the substance-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 irritable symptoms occurring during intoxication in a man with a

severe cocaine use disorder, the diagnosis is 292.84 cocaine-induced bipolar and related

disorder, with onset during intoxication. An additional diagnosis of 304.20 severe cocaine

use disorder is also given. When more than one substance is judged to play a significant

role in the development of bipolar mood symptoms, each should be listed separately (e.g.,

292.84 methylphenidate-induced bipolar and related disorder, with onset during intoxication; 292.84 dexamethasone-induced bipolar and related disorder, with onset during intoxication).

ICD-10-CM. The name of the substance/medication-induced bipolar and related disorder begins with the specific substance (e.g., cocaine, dexamethasone) that is presumed to

be causing the bipolar mood 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 (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-induced

bipolar and related disorder, followed by the specification of onset (i.e., onset during intoxication, onset during withdrawal). For example, in the case of irritable symptoms occurring during intoxication in a man with a severe cocaine use disorder, the diagnosis is

F14.24 severe cocaine use disorder with cocaine-induced bipolar and related disorder,

with onset during intoxication. A separate diagnosis of the comorbid severe cocaine use

disorder is not given. If the substance-induced bipolar and related disorder 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., F15.94 amphetamine-induced bipolar

and related disorder, with onset during intoxication). When more than one substance is

judged to play a significant role in the development of bipolar mood symptoms, each

should be listed separately (e.g., F15.24 severe methylphenidate use disorder with methylphenidate-induced bipolar and related disorder, with onset during intoxication; F19.94

dexamethasone-induced bipolar and related disorder, with onset during intoxication).

Diagnostic Features

The diagnostic features of substance/medication-induced bipolar and related disorder are essentially the same as those for mania, hypomania, or depression. A key exception to the diagnosis of substance/medication-induced bipolar and related disorder is the case of hypomania

or mania that occurs after antidepressant medication use or other treatments and persists beyond the physiological effects of the medication. This condition is considered an indicator of

true bipolar disorder, not substance/medication-induced bipolar and related disorder. Similarly, individuals with apparent electroconvulsive therapy-induced manic or hypomanie episodes that persist beyond the physiological effects of the treatment are diagnosed with

bipolar disorder, not substance/medication-induced bipolar ^ d related disorder.

Side effects of some antidepressants and other psychotropic drugs (e.g., edginess, agitation) may resemble the primary symptoms of a manic syndrome, but they are fundamentally distinct from bipolar symptoms and are insufficient for the diagnosis. That is, the

criterion symptoms of mania/hypomania have specificity (simple agitation is not the same

as excess involvement in purposeful activities), and a sufficient number of symptoms

must be present (not just one or two symptoms) to make these diagnoses. In particular, the

appearance of one or two nonspecific sjonptoms—irritability, edginess, or agitation during

antidepressant treatment—in the absence of a full manic or hypomanie syndrome should

not be taken to support a diagnosis of a bipolar disorder.

Associated Features Supporting Diagnosis

Etiology (causally related to the use of psychotropic medications or substances of abuse

based on best clinical evidence) is the key variable in this etiologically specified form of bipolar disorder. Substances/medications that are typically considered to be associated

with substance/medication-induced bipolar and related disorder include the stimulant

class of drugs, as well as phencyclidine and steroids; however, a number of potential substances continue to emerge as new compounds are synthesized (e.g., so-called bath salts).

A history of such substance use may help increase diagnostic certainty.

Prevaience

There are no epidemiological studies of substance/medication-induced mania or bipolar

disorder. Each etiological substance may have its own individual risk of inducing a bipolar (manic/hypomanie) disorder.

Deveiopment and Course

In phencyclidine-induced mania, the initial presentation may be one of a delirium with affective features, which then becomes an atypically appearing manic or mixed manic state.

This condition follows the ingestion or inhalation quickly, usually within hours or, at the

most, a few dayâ^ In stimulant-induced manic or hypomanie states, the response is in minutes to 1 hour after one or several ingestions or injections. The episode is very brief and

typically resolves over 1-2 days. With corticosteroids and some immunosuppressant

medications, the mania (or mixed or depressed state) usually follows several days of ingestion, and the higher doses appear to have a much greater likelihood of producing bipolar symptoms.

Diagnostic iVlari(ers

Determination of the substance of use can be made through markers in the blood or urine

to corroborate diagnosis.

Differentiai Diagnosis

Substance/medication-induced bipolar and related disorder should be differentiated

from other bipolar disorders, substance intoxication or substance-induced delirium, and

medication side effects (as noted earlier). A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully

syndromal level beyond the physiological effect of that treatment is sufficient evidence for

a bipolar I diagnosis. A full hypomanie episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level

beyond the physiological effect of that treatment is sufficient evidence for a bipolar II diagnosis only if preceded by a major depressive episode.

Comorbidity

Comorbidities are those associated with the use of illicit substances (in the case of illegal

stimulants or phencyclidine) or diversion of prescribed stimulants. Comorbidities related

to steroid or immunosuppressant medications are those medical indications for these

preparations. Delirium can occur before or along with manic symptoms in individuals ingesting phencyclidine or those who are prescribed steroid medications or other immunosuppressant medications.

Bipolar and Related Disorder

Due to Another Medical Condition

Diagnostic Criteria

A. A prominent and persistent period of abnormally elevated, expansive, or irritable mood

and abnormally increased activity or energy that predominates in the clinical picture.

B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition.

C. The disturbance is not better explained by another mental disorder.

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning, or necessitates hospitalization to prevent harm to self or others, or there are psychotic features.

Coding note: The ICD-9-CM code for bipolar and related disorder due to another medical

condition is 293.83, which is assigned regardless of the specifier. The ICD-10-CM code

depends on the specifier (see below).

Specify if:

(F06.33) With manic features: Full criteria are not met for a manic or hypomanie episode.

(F06.33) With manic- or hypomanic-iii<e episode: Full criteria are met except Criterion D for a manic episode or except Criterion F for a hypomanie episode.

(F06.34) With mixed features: Symptoms of depression are also present but do not

predominate in the clinical picture.

Coding note: Include the name of the other medical condition in the name of the mental

disorder (e.g., 293.83 [F06.33] bipolar disorder due to hyperthyroidism, with manic features). The other medical condition should also be coded and listed separately immediately before the bipolar and related disorder due to the medical condition (e.g., 242.90

[E05.90] hyperthyroidism; 293.83 [F06.33] bipolar disorder due to hyperthyroidism, with

manic features).

Diagnostic Features

The essential features of bipolar and related disorder due to another medical condition are

presence of a prominent and persistent period of abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy predominating in the clinical picture that is attributable to another medical condition (Criterion B). In most cases the manic

or hypomanie picture may appear during the initial presentation of the medical condition

(i.e., within 1 month); however, there are exceptions, especially in chronic medical conditions that might worsen or relapse and herald the appearance of the manic or hypomanie

picture. Bipolar and related disorder due to another medical condition would not be diagnosed when the manic or hypomanie episodes definitely preceded the medical condition,

since the proper diagnosis would be bipolar disorder (except in the unusual circumstance

in which all preceding manic or hypomanie episodes—or, when only one such episode has

occurred, the preceding manic or hypomanie episode—were associated with ingestion of

a substance/medication). The diagnosis of bipolar and related disorder due to another

medical condition should not be made during the course of a delirium (Criterion D). The

manic or hypomanie episode in bipolar and related disorder due to another medical condition must cause clinically significant distress or impairment in social, occupational, or

other important areas of functioning to qualify for this diagnosis (Criterion E).

Associated Features Supporting Diagnosis

Etiology (i.e., a causal relationship to another medical condition based on best clinical evidence) is the key variable in this etiologically specified form of bipolar disorder. The listing of medical conditions that are said to be able to induce mania is never complete, and

the clinician's best judgment is the essence of this diagnosis. Among the best known of the

medical conditions that can cause a bipolar manic or hypomanie condition are Cushing's

disease and multiple sclerosis, as well as stroke and traumatic brain injuries.

Deveiopment and Course

Bipolar and related disorder due to another medical condition usually has its onset acutely

or subacutely within the first weeks or month of the onset of the associated medical condition. However, this is not always the case, as a worsening or later relapse of the associated medical condition may precede the onset of the manic or hypomanie syndrome. The

clinician must make a clinical judgment in these situations about whether the medical condition is causative, based on temporal sequence as well as plausibility of a causal relation­

ship. Finally, the condition may remit before or just after the medical condition remits,

particularly wh^n treatment of the manic/hypomanie symptoms is effective.

Culture-Related Diagnostic Issues

Culture-related differences, to the extent that there is any evidence, pertain to those associated with the medical condition (e.g., rates of multiple sclerosis and stroke vary around

the world based on dietary, genetic factors, and other environmental factors).

Gender-Related Diagnostic Issues

Gender differences pertain to those associated with the medical condition (e.g., systemic

lupus erythematosus is more common in females; stroke is somewhat more common in

middle-age males compared with females).

Diagnostic Markers

Diagnostic markers pertain to those associated with the medical condition (e.g., steroid

levels in blood or urine to help corroborate the diagnosis of Cushing's disease, which can

be associated with manic or depressive syndromes; laboratory tests confirming the diagnosis of multiple sclerosis).

Functional Consequences of Bipolar and Related

Disorder Due to Another Medical Condition

Functional consequences of the bipolar symptoms may exacerbate impairments associated with the medical condition and may incur worse outcomes due to interference with

medical treatment. In general, it is believed, but not established, that the illness, when induced by Cushing's disease, will not recur if the Cushing's disease is cured or arrested.

However, it is also suggested, but not established, that mood syndromes, including depressive and manic/hypomanie ones, may be episodic (i.e., recurring) with static brain injuries and other central nervous system diseases.

Differential Diagnosis

Symptoms of delirium, catatonia, and acute anxiety. It is important to differentiate

symptoms of mania from excited or hypervigilant delirious symptoms; from excited catatonic symptoms; and from agitation related to acute anxiety states.

Medication-induced depressive or manic symptoms. An important differential diagnostic observation is that the other medical condition may be treated with medications

(e.g., steroids or alpha-interferon) that can induce depressive or manic symptoms. In these

cases, clinical judgment using all of the evidence in hand is the best way to try to separate

the most likely and/or the most important of two etiological factors (i.e., association with

the medical condition vs. a substance/medication-induced syndrome). The differential diagnosis of the associated medical conditions is relevant but largely beyond the scope of the

present manual.

Comorbidity

Conditions comorbid with bipolar and related disorder due to another medical condition

are those associated with the medical conditions of etiological relevance. Delirium can occur before or along with manic symptoms in individuals with Cushing's disease.

Other Specified Bipolar and Related Disorder

296.89 (F31.89)

This category applies to presentations in which symptoms characteristic of a bipolar and

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 of the disorders in the bipolar and related disorders diagnostic class. The other

specified bipolar and related disorder category is used in situations in which the clinician

chooses to communicate the specific reason that the presentation does not meet the criteria for any specific bipolar and related disorder. This is done by recording “other specified bipolar and related disorder” followed by the specific reason (e.g., “short-duration

cyclothymia”).

Examples of presentations that can be specified using the “other specified” designation

include the following:

1. Short-duration hypomanie episodes (2-3 days) and major depressive episodes: A

lifetime history of one or more major depressive episodes in individuals whose presentation has never met full criteria for a manic or hypomanie episode but who have experienced

two or more episodes of short-duration hypomania that meet the full symptomatic criteria

for a hypomanie episode but that only last for 2-3 days. The episodes of hypomanie symptoms do not overlap in time with the major depressive episodes, so the disturbance does

not meet criteria for major depressive episode, with mixed features.

2. Hypomanie episodes with insufficient symptoms and major depressive episodes: A lifetime history of one or more major depressive episodes in individuals

whose presentation has never met full criteria for a manic or hypomanie episode but

who have experienced one or more episodes of hypomania that do not meet full symptomatic criteria (i.e., at least 4 consecutive days of elevated mood and one or two of

the other symptoms of a hypomanie episode, or irritable mood and two or three of the

other symptoms of a hypomanie episode). The episodes of hypomanie symptoms do

not overlap in time with the major depressive episodes, so the disturbance does not

meet criteria for major depressive episode, with mixed features.

3. Hypomanie episode without prior major depressive episode: One or more hypomanic episodes in an individual whose presentation has never met full criteria for a major depressive episode or a manic episode. If this occurs in an individual with an

established diagnosis of persistent depressive disorder (dysthymia), both diagnoses

can be concurrently applied during the periods when the full criteria for a hypomanie

episode are met.

4. Short-duration eyelothymia (less than 24 months): Multiple episodes of hypomanie

symptoms that do not meet criteria for a hypomanie episode and multiple episodes of depressive symptoms that do not meet criteria for a major depressive episode that persist

over a period of less than 24 months (less than 12 months for children or adolescents)

in an individual whose presentation has never met full criteria for a major depressive,

manic, or hypomanie episode and does not meet criteria for any psychotic disorder. During the course of the disorder, the hypomanie or depressive symptoms are present for

more days than not, the individual has not been without symptoms for more than 2 months

at a time, and the symptoms cause clinically significant distress or impairment.

Unspecified Bipolar and Related Disorder

_________________________________ V_______________________________________________________________________________________________________________________________________________________

296.80 (F31.9)

This category applies to presentations in which symptoms characteristic of a bipolar and

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 of the disorders in the bipolar and related disorders diagnostic class. The unspecified bipolar and related disorder category is used in situations in which the clinician chooses not to specify the reason that the criteria are not met for a specific bipolar and related

disorder, and includes presentations in which there is insufficient information to make a

more specific diagnosis (e.g., in emergency room settings).

Specifiers for Bipolar and Related Disorders

Specify if:

With anxious distress: The presence of at least two of the following symptoms during

the majority of days of the current or most recent episode of mania, hypomania, or depression:

1. Feeling keyed up or tense.

2. Feeling unusually restless.

3. Difficulty concentrating because of worry.

4. Fear that something awful may happen.

5. Feeling that the individual might lose control of himself or herself.

Specify current severity:

lUlild: Two symptoms.

lUloderate: Three symptoms.

Moderate-severe: Four or five symptoms.

Severe: Four or five symptoms with motor agitation.

Note: Anxious distress has been noted as a prominent feature of both bipolar and

major depressive disorder in both primary care and specialty mental health settings. High levels of anxiety have been associated with higher suicide risk, longer

duration of illness, and greater likelihood of treatment nonresponse. As a result, it

is clinically useful to specify accurately the presence and severity levels of anxious

distress for treatment planning and monitoring of response to treatment.

With mixed features: The mixed features specifier can apply to the current manic, hypomanie, or depressive episode in bipolar I or bipolar II disorder:

IManic or hypomanie episode, with mixed features:

A. Full criteria are met for a manic episode or hypomanie episode, and at least

three of the following symptoms are present during the majority of days of the

current or most recent episode of mania or hypomania:

1. Prominent dysphoria or depressed mood as indicated by either subjective

report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).

2. Diminished interest or pleasure in all, or almost all, activities (as indicated by

either subjective account or observation made by others).

3. Psychomotor retardation nearly every day (observable by others; not merely

subjective feelings of being slowed down).

4. Fatigue or loss of energy.

5. Feelings of worthlessness or excessive or inappropriate guilt (not merely

self-reproach or guilt about being sick).

6. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B. Mixed symptoms are observable by others and represent a change from the

person’s usual behavior.

C. For individuals whose symptoms meet full episode criteria for both mania and

depression simultaneously, the diagnosis should be manic episode, with mixed

features, due to the marked impairment and clinical severity of full mania.

D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment).

Depressive episode, witli mixed features:

A. Full criteria are met for a major depressive episode, and at least three of the following manic/hypomanic symptoms are present during the majority of days of

the current or most recent episode of depression:

1. Elevated, expansive mood.

2. Inflated self-esteem or grandiosity.

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Increase in energy or goal-directed activity (either socially, at work or school,

or sexually).

6. Increased or excessive involvement in activities that have a high potential

for painful consequences (e.g., engaging in unrestrained buying sprees,

sexual indiscretions, or foolish business investments).

7. Decreased need for sleep (feeling rested despite sleeping less than usual;

to be contrasted with insomnia).

B. Mixed symptoms are observable by others and represent a change from the

person’s usual behavior.

C. For individuals whose symptoms meet full episode criteria for both mania and

depression simultaneously, the diagnosis should be manic episode, with mixed

features.

D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment).

Note: Mixed features associated with a major depressive episode have been found

to be a significant risk factor for the development of bipolar I or bipolar II disorder.

As a result, it is clinically useful to note the presence of this specifier for treatment

planning and monitoring of response to treatment.

Witli rapid cycling (can be applied to bipolar I or bipolar II disorder): Presence of at

least four mood episodes in the previous 12 months that meet the criteria for manic,

hypomanie, or major depressive episode.

Note: Episodes are demarcated by either partial or full remissions of at least 2 months

or a switch to an episode of the opposite polarity (e.g., major depressive episode to

manic episode).

Note: The essential feature of a rapid-cycling bipolar disorder is the occurrence of

at least four mood episodes during the previous 12 months. These episodes can

occur in any combination and order. The episodes must meet both the duration and

symptom number criteria for a major depressive, manic, or hypomanie episode and

must be demarcated by either a period of full remission or a switch to an episode

of the opposite polarity. Manic and hypomanie episodes are counted as being on

the same pole. Except for the fact that they occur more frequently, the episodes that

occur in a rapid-cycling pattern are no different from those that occur in a non-rapidcycling pattern. Mood episodes that count toward defining a rapid-cycling pattern

exclude those episodes directly caused by a substance (e.g., cocaine, corticosteroids) or another medical condition.

With melancholic features:

A. One of the following is present during the most severe period of the current episode;

1. Loss of pleasure in all, or almost all, activities.

2. Lack of reactivity to usually pleasurable stimuli (does not feel much better, even

temporarily, when something good happens).

B. Three (or more) of the following:

1. A distinct quality of depressed mood characterized by profound despondency,

despair, and/or moroseness or by so-called empty mood.

2. Depression that is regularly worse in the morning.

3. Early-morning awakening (i.e., at least 2 hours before usual awakening).

4. Marked psychomotor agitation or retardation.

5. Significant anorexia or weight loss.

6. Excessive or inappropriate guilt.

Note: The specifier “with melancholic features” is applied if these features are present at the most severe stage of the episode. There is a near-complete absence of

the capacity for pleasure, not merely a diminution. A guideline for evaluating the

lack of reactivity of mood is that even highly desired events are not associated with

marked brightening of mood. Either mood does not brighten at all, or it brightens

only partially (e.g., up to 20% -40% of normal for only minutes at a time). The “distinct quality” of mood that is characteristic of the “with melancholic features” specifier is experienced as qualitatively different from that during a nonmelancholic

depressive episode. A depressed mood that is described as merely more severe,

longer lasting, or present without a reason is not considered distinct in quality. Psychomotor changes are nearly always present and are observable by others.

Melancholic features exhibit only a modest tendency to repeat across episodes

in the same individual. They are more frequent in inpatients, as opposed to outpatients; are less likely to occur in milder than in more severe major depressive episodes; and are more likely to occur in those with psychotic features.

With atypical features: This specifier can be applied when these features predominate during the majority of days of the current or most recent major depressive episode.

A. Mood reactivity (i.e., mood brightens in response to actual or potential positive

events).

B. Two (or more) of the following features:

1. Significant weight gain or increase in appetite.

2. Hypersomnia.

3. Leaden paralysis (i.e., heavy, leaden feelings in arms or legs).

4. A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational

impairment.

C. Criteria are not met for “with melancholic features” or “with catatonia” during the

same episode.

Note: “Atypical depression” has historical significance (i.e., atypical in contradistinction to the more classical agitated, “endogenous” presentations of depression

that were the norm when depression was rarely diagnosed in outpatients and almost never in adolescents or younger adults) and today does not connote an uncommon or unusual clinical presentation as the term might imply.

Mood reactivity is the capacity to be cheered up when presented with positive

events (e.g., a visit from children, compliments from others). Mood may become

euthymie (not sad) even for extended periods of time if the external circumstances

remain favorable. Increased appetite may be manifested by an obvious increase in

food intake or by weight gain. Hypersomnia may include either an extended period

of nighttime sleep or daytime napping that totals at least 10 hours of sleep per day

(or at least 2 hours more than when not depressed). Leaden paralysis is defined as

feeling heavy, leaden, or weighted down, usually in the arms or legs. This sensation

is generally present for at least an hour a day but often lasts for many hours at a

time. Unlike the other atypical features, pathological sensitivity to perceived interpersonal rejection is a trait that has an early onset and persists throughout most of

adult life. Rejection sensitivity occurs both when the person is and is not depressed,

though it may be exacerbated during depressive periods.

With psychotic features: Delusions or hallucinations are present at any time in the

episode. If psychotic features are present, specify if mood-congruent or mood-incongruent:

With mood-congruent psychotic features: During manic episodes, the content of all delusions and hallucinations is consistent with the typical manic

themes of grandiosity, invulnerability, etc., but may also include themes of suspiciousness or paranoia, especially with respect to others’ doubts about the individual’s capacities, accomplishments, and so forth.

With mood-incongruent psychotic features: The content of delusions and

hallucinations is inconsistent with the episode polarity themes as described

above, or the content is a mixture of mood-incongruent and mood-congruent

themes.

With catatonia: This specifier can apply to an episode of mania or depression if catatonic features are present during most of the episode. See criteria for catatonia associated with a mental disorder in the chapter “Schizophrenia Spectrum and Other

Psychotic Disorders.”

With péripartum onset: This specifier can be applied to the current or, if the full criteria are not currently met for a mood episode, most recent episode of mania, hypomania, or major depression in bipolar I or bipolar I! disorder if onset of mood symptoms

occurs during pregnancy or in the 4 weeks following delivery.

Note: Mood episodes can have their onset either during pregnancy or postpartum.

Although the estimates differ according to the period of follow-up after delivery, between 3% and 6% of women will experience the onset of a major depressive episode during pregnancy or in the weeks or months following delivery. Fifty percent

of “postpartum” major depressive episodes actually begin prior to delivery. Thus,

these episodes are referred to collectively as péripartum episodes. Women with

péripartum major depressive episodes often have severe anxiety and even panic

attacks. Prospective studies have demonstrated that mood and anxiety symptoms

during pregnancy, as well as the “baby blues,” increase the risk for a postpartum

major depressive episode.

Peripartum-onset mood episodes can present either with or without psychotic

features^ Infanticide is most often associated with postpartum psychotic episodes

that are characterized by command hallucinations to kill the infant or delusions that

the infant is possessed, but psychotic symptoms can also occur in severe postpartum mood episodes without such specific delusions or hallucinations.

Postpartum mood (major depressive or manic) episodes with psychotic features

appear to occur in from 1 in 500 to 1 in 1,000 deliveries and may be more common

in primiparous women. The risk of postpartum episodes with psychotic features is

particularly increased for women with prior postpartum mood episodes but is also

elevated for those with a prior history of a depressive or bipolar disorder (especially

bipolar I disorder) and those with a family history of bipolar disorders.

Once a woman has had a postpartum episode with psychotic features, the risk

of recurrence with each subsequent delivery is between 30% and 50%. Postpartum

episodes must be differentiated from delirium occurring in the postpartum period,

which is distinguished by a fluctuating level of awareness or attention. The postpartum period is unique with respect to the degree of neuroendocrine alterations and

psychosocial adjustments, the potential impact of breast-feeding on treatment planning, and the long-term implications of a history of postpartum mood disorder on subsequent family planning.

With seasonal pattern: This specifier applies to the lifetime pattern of mood episodes.

The essential feature is a regular seasonal pattern of at least one type of episode (i.e.,

mania, hypomania, or depression). The other types of episodes may not follow this pattern. For example, an individual may have seasonal manias, but his or her depressions

do not regularly occur at a specific time of year.

A. There has been a regular temporal relationship between the onset of manic, hypomanic, or major depressive episodes and a particular time of the year (e.g., in the

fall or winter) in bipolar I or bipolar II disorder.

Note: Do not include cases in which there is an obvious effect of seasonally related

psychosocial stressors (e.g., regularly being unemployed every winter).

B. Full remissions (or a change from major depression to mania or hypomania or vice

versa) also occur at a characteristic time of the year (e.g., depression disappears

in the spring).

C. In the last 2 years, the individual’s manic, hypomanie, or major depressive episodes

have demonstrated a temporal seasonal relationship, as defined above, and no

non-seasonal episodes of that polarity have occurred during that 2-year period.

D. Seasonal manias, hypomanias, or depressions (as described above) substantially

outnumber any nonseasonal manias, hypomanias, or depressions that may have

occurred over the individual’s lifetime.

Note: This specifier can be applied to the pattern of major depressive episodes in

bipolar I disorder, bipolar II disorder, or major depressive disorder, recurrent. The

essential feature is the onset and remission of major depressive episodes at characteristic times of the year. In most cases, the episodes begin in fall or winter and

remit in spring. Less commonly, there may be recurrent summer depressive episodes. This pattern of onset and remission of episodes must have occurred during

at least a 2-year period, without any nonseasonal episodes occurring during this

period. In addition, the seasonal depressive episodes must substantially outnumber any nonseasonal depressive episodes over the individual’s lifetime.

This specifier does not apply to those situations in which the pattern is better explained by seasonally linked psychosocial stressors (e.g., seasonal unemployment

or school schedule). Major depressive episodes that occur in a seasonal pattern

are often characterized by prominent energy, hypersomnia, overeating, weight

gain, and a craving for carbohydrates. It is unclear whether a seasonal pattern is

more likely in recurrent major depressive disorder or in bipolar disorders. However,

within the bipolar disorders group, a seasonal pattern appears to be more likely in

bipolar II disorder than in bipolar I disorder. In some individuals, the onset of manic

or hypomanie episodes may also be linked to a particular season.

The prevalence of winter-type seasonal pattern appears to vary with latitude,

age, and sex. Prevalence increases with higher latitudes. Age is also a strong predictor of seasonality, with younger persons at higher risk for winter depressive episodes.

Specify if:

In partial remission: Symptoms of the immediately previous manic, hypomanie, or

depressive episode are present, but full criteria are not met, or there is a period lasting

less than 2 months without any significant symptoms of a manic, hypomanie, or major

depressive episode following the end of such an episode.

In full remission: During the past 2 months, no significant signs or symptoms of the

disturbance were present.

Specify current severity:

Severity is based on the number of criterion symptoms, the severity of those symptoms,

and the degree of functional disability.

Mild: Few, if any, symptoms in excess of those required to meet the diagnostic criteria

are present, the intensity of the symptoms is distressing but manageable, and the

symptoms result in minor impairment in social or occupational functioning.

Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for “mild” and “severe.”

Severe: The number of symptoms is substantially in excess of those required to make

the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning.

D eprG SSiV G diSO rdG rS include disruptive mood dysregulation disorder, major

depressive disorder (including major depressive episode), persistent depressive disorder

(dysthymia), premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, other specified depressive disorder, and imspecified depressive disorder. Unlike in DSM-IV, this chapter

"Depressive Disorders" has been separated from the previous chapter "Bipolar and Related Disorders." The common feature of all of these disorders is the presence of sad,

empty, or irritable mood, accompanied by somatic and cognitive changes that significantly affect the individual's capacity to function. What differs among them are issues of

duration, timing, or presumed etiology.

In order to address concerns about the potential for the overdiagnosis of and treatment

for bipolar disorder in children, a new diagnosis, disruptive mood dysregulation disorder,

referring to the presentation of children with persistent irritability and frequent episodes

of extreme behavioral dyscontrol, is added to the depressive disorders for children up to

12 years of age. Its placement in this chapter reflects the finding that children with this

symptom pattern typically develop unipolar depressive disorders or anxiety disorders,

rather than bipolar disorders, as they mature into adolescence and adulthood.

Major depressive disorder represents the classic condition in this group of disorders. It

is characterized by discrete episodes of at least 2 weeks' duration (although most episodes

last considerably longer) involving clear-cut changes in affect, cognition, and neurovegetative functions and inter-episode remissions. A diagnosis based on a single episode is

possible, although the disorder is a recurrent one in the majority of cases. Careful consideration is given to the delineation of normal sadness and grief from a major depressive episode. Bereavement may induce great suffering, but it does not typically induce an episode

of major depressive disorder. When they do occur together, the depressive symptoms and

functional impairment tend to be more severe and the prognosis is worse compared with

bereavement that is not accompanied by major depressive disorder. Bereavement-related

depression tends to occur in persons with other vulnerabilities to depressive disorders,

and recovery may be facilitated by antidepressant treatment.

A more chronic form of depression, persistent depressive disorder (dysthymia), can be

diagnosed when the mood disturbance continues for at least 2 years in adults or 1 year in

children. This diagnosis, new in DSM-5, includes both the DSM-IV diagnostic categories of

chronic major depression and dysthymia.

After careful scientific review of the evidence, premenstrual dysphoric disorder has

been moved from an appendix of DSM-IV ("Criteria Sets and Axes Provided for Further

Study") to Section II of DSM-5. Almost 20 years of additional of research on this condition

has confirmed a specific and treatment-responsive form of depressive disorder that begins

sometime following ovulation and remits within a few days of menses and has a marked

impact on functioning.

A large number of substances of abuse, some prescribed medications, and several

medical conditions can be associated with depression-like phenomena. This fact is recognized in the diagnoses of substance/medication-induced depressive disorder and depressive disorder due to another medical condition.

Disruptive Mood Dysregulation Disorder

Diagnostic Criteria 296.99 (F34.8)

A. Severe recurrent temper outbursts manifested verbally (e.g., verbal rages) and/or behaviorally (e.g., physical aggression toward people or property) that are grossly out of

proportion in intensity or duration to the situation or provocation.

B. The temper outbursts are inconsistent with developmental level.

C. The temper outbursts occur, on average, three or more times per week.

D. The mood between temper outbursts is persistently irritable or angry most of the day,

nearly every day, and is observable by others (e.g., parents, teachers, peers).

E. Criteria A-D have been present for 12 or more months. Throughout that time, the individual has not had a period lasting 3 or more consecutive months without all of the

symptoms in Criteria A-D.

F. Criteria A and D are present in at least two of three settings (i.e., at home, at school,

with peers) and are severe in at least one of these.

G. The diagnosis should not be made for the first time before age 6 years or after age 18

years.

H. By history or observation, the age at onset of Criteria A-E is before 10 years.

I. There has never been a distinct period lasting more than 1 day during which the full

symptom criteria, except duration, for a manic or hypomanie episode have been met.

Note: Developmentally appropriate mood elevation, such as occurs in the context of a

highly positive event or its anticipation, should not be considered as a symptom of mania or hypomania.

J. The behaviors do not occur exclusively during an episode of major depressive disorder

and are not better explained by another mental disorder (e.g., autism spectrum disorder, posttraumatic stress disorder, separation anxiety disorder, persistent depressive

disorder [dysthymia]).

Note: This diagnosis cannot coexist with oppositional defiant disorder, intermittent explosive disorder, or bipolar disorder, though it can coexist with others, including major

depressive disorder, attention-deficit/hyperactivity disorder, conduct disorder, and

substance use disorders. Individuals whose symptoms meet criteria for both disruptive

mood dysregulation disorder and oppositional defiant disorder should only be given the

diagnosis of disruptive mood dysregulation disorder. If an individual has ever experienced a manic or hypomanie episode, the diagnosis of disruptive mood dysregulation

disorder should not be assigned.

K. The symptoms are not attributable to the physiological effects of a substance or to another medical or neurological condition.

Diagnostic Features

The core feature of disruptive mood dysregulation disorder is chronic, severe persistent irritabihty. This severe irritability has two prominent clinical manifestations, the first of

which is frequent temper outbursts. These outbursts typically occur in response to frustration and can be verbal or behavioral (the latter in the form of aggression against property, self, or others). They must occur frequently (i.e., on average, three or more times per

week) (Criterion C) over at least 1 year in at least two settings (Criteria E and F), such as in

the home and at school, and they must be developmentally inappropriate (Criterion B).

The second manifestation of severe irritability consists of chronic, persistently irritable or

angry mood that is present between the severe temper outbursts. This irritable or angry

mood must be characteristic of the child, being present most of the day, nearly every day,

and noticeable by others in the child's environment (Criterion D).

The clinical presentation of disruptive mood dysregulation disorder must be carefully

distinguished from presentations of other, related conditions, particularly pediatric bipolar disorder. In fact, disruptive mood dysregulation disorder was added to DSM-5 to

address the considerable concern about the appropriate classification and treatment of

children who present with chronic, persistent irritability relative to children who present

with classic (i.e., episodic) bipolar disorder.

Some researchers view severe, non-episodic irritability as characteristic of bipolar disorder in children, although both DSM-IV and DSM-5 require that both children and adults

have distinct episodes of mania or hypomania to qualify for the diagnosis of bipolar I disorder. During the latter decades of the 20th century, this contention by researchers that

severe, nonepisodic irritability is a manifestation of pediatric mania coincided with an upsurge in the rates at which clinicians assigned the diagnosis of bipolar disorder to their

pediatric patients. This sharp increase in rates appears to be attributable to clinicians combining at least two clinical presentations into a single category. That is, both classic, episodic presentations of mania and non-episodic presentations of severe irritability have

been labeled as bipolar disorder in children. In DSM-5, the term bipolar disorder is explicitly

reserved for episodic presentations of bipolar symptoms. DSM-IV did not include a diagnosis designed to capture youths whose hallmark symptoms consisted of very severe, nonepisodic irritability, whereas DSM-5, with the inclusion of disruptive mood dysregulation

disorder, provides a distinct category for such presentations.

Prevalence

Disruptive mood dysregulation disorder is common among children presenting to pediatric mental health clinics. Prevalence estimates of the disorder in the community are unclear. Based on rates of chronic and severe persistent irritability, which is the core feature

of the disorder, the overall 6-month to 1-year period-prevalence of disruptive mood dysregulation disorder among children and adolescents probably falls in the 2%-5% range.

However, rates are expected to be higher in males and school-age children than in females

and adolescents.

Development and Course

The onset of disruptive mood dysregulation disorder must be before age 10 years, and the

diagnosis should not be applied to children with a developmental age of less than 6 years.

It is unknown whether the condition presents only in this age-delimited fashion. Because

the symptoms of disruptive mood dysregulation disorder are likely to change as children

mature, use of the diagnosis should be restricted to age groups similar to those in which

validity has been established (7-18 years). Approximately half of children with severe,

chronic irritability will have a presentation that continues to meet criteria for the condition

1 year later. Rates of conversion from severe, nonepisodic irritability to bipolar disorder

are very low. Instead, children with chronic irritability are at risk to develop unipolar depressive and/or anxiety disorders in adulthood.

Age-related variations also differentiate classic bipolar disorder and disruptive mood

dysregulation disorder. Rates of bipolar disorder generally are very low prior to adolescence (<1%), with a steady increase into early adulthood (l%-2% prevalence). Disruptive

mood dysregulation disorder is more common than bipolar disorder prior to adolescence,

and symptoms of the condition generally become less common as children transition into

adulthood.

Risk and Prognostic Factors

Temperamental. Children with chronic irritability typically exhibit complicated psychiatric histories. In such children, a relatively extensive history of chronic irritability is

common, typically manifesting before full criteria for the syndrome are met. Such prediagnostic presentations may have qualified for a diagnosis of oppositional defiant disorder.

Many children with disruptive mood dysregulation disorder have symptoms that also

meet criteria for attention-deficit/hyperactivity disorder (ADHD) and for an anxiety disorder, with such diagnoses often being present from a relatively early age. For some children, the criteria for major depressive disorder may also be met.

Genetic and physiological. In terms of familial aggregation and genetics, it has been

suggested that children presenting with chronic, non-episodic irritability can be differentiated from children with bipolar disorder in their family-based risk. However, these two

groups do not differ in familial rates of anxiety disorders, unipolar depressive disorders,

or substance abuse. Compared with children with pediatric bipolar disorder or other mental illnesses, those with disruptive mood dysregulation disorder exhibit both commonalities and differences in information-processing deficits. For example, face-emotion

labeling deficits, as well as perturbed decision making and cognitive control, are present in

children with bipolar disorder and chronically irritable children, as well as in children

with some other psychiatric conditions. There is also evidence for disorder-specific dysfunction, such as during tasks assessing attention deployment in response to emotional

stimuli, which has demonstrated unique signs of dysfunction in children with chronic irritability.

Gender-Related Diagnostic issues

Children presenting to clinics with features of disruptive mood dysregulation disorder are

predominantly male. Among community samples, a male preponderance appears to be

supported. This difference in prevalence between males and females differentiates disruptive mood dysregulation disorder from bipolar disorder, in which there is an equal gender

prevalence.

Suicide Risic

In general, evidence documenting suicidal behavior and aggression, as well as other severe functional consequences, in disruptive mood dysregulation disorder should be noted

when evaluating children with chronic irritability.

Functionai Consequences of

Disruptive iVlood Dysreguiation Disorder

Chronic, severe irritability, such as is seen in disruptive mood dysregulation disorder, is

associated with marked disruption in a child's family and peer relationships, as well as in

school performance. Because of their extremely low frustration tolerance, such children

generally have difficulty succeeding in school; they are often unable to participate in the

activities typically enjoyed by healthy children; their family life is severely disrupted by

their outbursts and irritability; and they have trouble initiating or sustaining friendships.

Levels of dysfunction in children with bipolar disorder and disruptive mood dysregulation

disorder are generally comparable. Both conditions cause severe disruption in the lives of

the affected individual and their families. In both disruptive mood dysregulation disorder

and pediatric bipolar disorder, dangerous behavior, suicidal ideation or suicide attempts,

severe aggression, and psychiatric hospitalization are common.

Differential Diagnosis

Because chronically irritable children and adolescents typically present with complex histories, the diagnosis of disruptive mood dysregulation disorder must be made while considering the presence or absence of multiple other conditions. Despite the need to consider

many other syndromes, differentiation of disruptive mood dysregulation disorder from bipolar disorder and oppositional defiant disorder requires particularly careful assessment.

Bipolar disorders. The central feature differentiating disruptive mood dysregulation disorder and bipolar disorders in children involves the longitudinal course of the core s}nTiptoms. In

children, as in adults, bipolar I disorder and bipolar Π disorder manifest as an episodic illness

with discrete episodes of mood perturbation that can be differentiated from the child's typical

presentation. The mood perturbation that occurs during a manic episode is distinctly different

from the child's usual mood. In addition, during a manic episode, the change in mood must be

accompanied by the onset, or worsening, of associated cognitive, behavioral, and physical

symptoms (e.g., distractibility, increased goal-directed activity), which are also present to a degree that is distinctly different from the child's usual baseline. Thus, in the case of a manic episode, parents (and, depending on developmental level, children) should be able to identify a

distinct time period during which the child's mood and behavior were markedly different

from usual. In contrast, the irritability of disruptive mood dysregulation disorder is persistent

and is present over many months; while it may wax and wane to a certain degree, severe irritability is characteristic of the child with disruptive mood dysregulation disorder. Thus, while

bipolar disorders are episodic conditions, disruptive mood dysregulation disorder is not. In

fact, the diagnosis of disruptive mood dysregulation disorder cannot be assigned to a child

who has ever experienced a fuU-duration hypomanie or manic episode (irritable or euphoric)

or who has ever had a manic or hypomanie episode lasting more than 1 day. Another central

differentiating feature between bipolar disorders and disruptive mood dysregulation disorder

is the presence of elevated or expansive mood and grandiosity. These symptoms are common

features of mania but are not characteristic of disruptive m ood dysregulation disorder.

Oppositional defiant disorder. While symptoms of oppositional defiant disorder typically do occur in children with disruptive mood dysregulation disorder, mood symptoms

of disruptive mood dysregulation disorder are relatively rare in children with oppositional defiant disorder. The key features that warrant the diagnosis of disruptive mood

dysregulation disorder in children whose symptoms also meet criteria for oppositional defiant disorder are the presence of severe and frequently recurrent outbursts and a persistent disruption in mood between outbursts. In addition, the diagnosis of disruptive mood

dysregulation disorder requires severe impairment in at least one setting (i.e., home,

school, or among peers) and mild to moderate impairment in a second setting. For this reason, while most children whose symptoms meet criteria for disruptive mood dysregulation disorder will also have a presentation that meets criteria for oppositional defiant

disorder, the reverse is not the case. That is, in only approximately 15% of individuals with

oppositional defiant disorder would criteria for disruptive mood dysregulation disorder

be met. Moreover, even for children in whom criteria for both disorders are met, only the

diagnosis of disruptive mood dysregulation disorder should be made. Finally, both the

prominent mood symptoms in disruptive mood dysregulation disorder and the high risk

for depressive and anxiety disorders in follow-up studies justify placement of disruptive

mood dysregulation disorder among the depressive disorders in DSM-5. (Oppositional

defiant disorder is included in the chapter "Disruptive, Impulse-Control, and Conduct

Disorders.") This reflects the more prominent mood component among individuals with

disruptive mood dysregulation disorder, as compared with individuals with oppositional

defiant disorder. Nevertheless, it also should be noted that disruptive mood dysregulation

disorder appears to carry a high risk for behavioral problems as well as mood problems.

Attention-deficit/hyperactivity disorder, major depressive disorder, anxiety disorders,

and autism spectrum disorder. Unlike children diagnosed with bipolar disorder or oppositional defiant disorder, a child whose symptoms meet criteria for disruptive mood

dysregulation disorder also can receive a comorbid diagnosis of ADHD, major depressive

disorder, and/or anxiety disorder. However, children whose irritability is present only in

the context of a major depressive episode or persistent depressive disorder (dysthymia)

should receive one of those diagnoses rather than disruptive mood dysregulation disorder. Children with disruptive mood dysregulation disorder may have symptoms that also

meet criteria for an anxiety disorder and can receive both diagnoses, but children whose irritability is manifest only in the context of exacerbation of an anxiety disorder should receive the relevant anxiety disorder diagnosis rather than disruptive mood dysregulation

disorder. In addition, children with autism spectrum disorders frequently present with

temper outbursts when, for example, their routines are disturbed. In that instance, the

temper outbursts would be considered secondary to the autism spectrum disorder, and

the child should not receive the diagnosis of disruptive mood dysregulation disorder.

Intermittent explosive disorder. Children with symptoms suggestive of intermittent

explosive disorder present with instances of severe temper outbursts, much like children

with disruptive mood dysregulation disorder. However, unlike disruptive mood dysregulation disorder, intermittent explosive disorder does not require persistent disruption in

mood between outbursts. In addition, intermittent explosive disorder requires only 3 months

of active symptoms, in contrast to the 12-month requirement for disruptive mood dysregulation disorder. Thus, these two diagnoses should not be made in the same child. For

children with outbursts and intercurrent, persistent irritability, only the diagnosis of disruptive mood dysregulation disorder should be made.

Comorbidity

Rates of comorbidity in disruptive mood dysregulation disorder are extremely high. It is

rare to find individuals whose symptoms meet criteria for disruptive mood dysregulation

disorder alone. Comorbidity between disruptive mood dysregulation disorder and other

DSM-defined syndromes appears higher than for many other pediatric mental illnesses;

the strongest overlap is with oppositional defiant disorder. Not only is the overall rate of

comorbidity high in disruptive mood dysregulation disorder, but also the range of comorbid illnesses appears particularly diverse. These children typically present to the clinic

with a wide range of disruptive behavior, mood, anxiety, and even autism spectrum

symptoms and diagnoses. However, children with disruptive mood dysregulation disorder should not have symptoms that meet criteria for bipolar disorder, as in that context,

only the bipolar disorder diagnosis should be made. If children have symptoms that meet

criteria for oppositional defiant disorder or intermittent explosive disorder and disruptive

mood dysregulation disorder, only the diagnosis of disruptive mood dysregulation disorder should be assigned. Also, as noted earlier, the diagnosis of disruptive mood dysregulation disorder should not be assigned if the symptoms occur only in an anxietyprovoking context, when the routines of a child with autism spectrum disorder or obsessive-compulsive disorder are disturbed, or in the context of a major depressive episode.

Major Depressive Disorder

Diagnostic Criteria

A. Five (or more) of the following symptoms have been present during the same 2-week

period and represent a change from previous functioning: at least one of the symptoms

is either (1) depressed mood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly attributable to another medical condition.

1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g.,

appears tearful). (Note: In children and adolescents, can be irritable mood.)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the

day, nearly every day (as indicated by either subjective account or observation).

3. Significant weight loss when not dieting or weight gain (e.g., a change of more than

5% of body weight in a month), or decrease or increase in appetite nearly every day.

(Note: In children, consider failure to make expected weight gain.)

4. Insomnia or hypersomnia nearly every day.

5. Psychomotor agitation or retardation nearly every day (observable by others, not

merely subjective feelings of restlessness or being slowed down).

6. Fatigue or loss of energy nearly every day.

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

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

C. The episode is not attributable to the physiological effects of a substance or to another

medical condition.

Note: Criteria A-C represent a major depressive episode.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A,

which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in

addition to the normal response to a significant loss should also be carefully considered. This

decision inevitably requires the exercise of clinical judgment based on the individual’s history

and the cultural norms for the expression of distress in the context of loss.^

D. The occurrence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or

other specified and unspecified schizophrenia spectrum and other psychotic disorders.

E. There has never been a manic episode or a hypomanie episode.

Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes

are substance-induced or are attributable to the physiological effects of another medical condition.

’ In distinguishing grief from a major depressive episode (MDE), it is useful to consider that in

grief the predominant affect is feelings of emptiness and loss, while in MDE it is persistent

depressed mood and the inability to anticipate happiness or pleasure. The dysphoria in grief is

likely to decrease in intensity over days to weeks and occurs in waves, the so-called pangs of

grief. These waves tend to be associated with thoughts or reminders of the deceased. The

depressed mood of MDE is more persistent and not tied to specific thoughts or preoccupations.

The pain of grief may be accompanied by positive emotions and humor that are uncharacteristic

of the pervasive unhappiness and misery characteristic of MDE. The thought content associated

with grief generally features a preoccupation with thoughts and memories of the deceased,

rather than the self-critical or pessimistic ruminations seen in MDE. In grief, self-esteem is generally preserved, whereas in MDE feelings of worthlessness and self-loathing are common. If selfderogatory ideation is present in grief, it typically involves perceived failings vis-à-vis the

deceased (e.g., not visiting frequently enough, not telling the deceased how much he or she was

loved). If a bereaved individual thinks about death and dying, such thoughts are generally

focused on the deceased and possibly about "joining" the deceased, whereas in MDE such

thoughts are focused on ending one's own life because of feeling worthless, undeserving of life,

or unable to cope with the pain of depression.

Coding and Recording Procedures

The diagnostic code for major depressive disorder is based on whether this is a single or

recurrent episode, current severity, presence of psychotic features, and remission status.

Current severity and psychotic features are only indicated if full criteria are currently met

for a major depressive episode. Remission specifiers are only indicated if the full criteria

are not currently met for a major depressive episode. Codes are as follows:

Severity/course specifier Single episode Recurrent episode*

Mild (p. 188) 296.21 (F32.0) 296.31 (F33.0)

Moderate (p. 188) 296.22 (F32.1) 296.32 (F33.1)

Severe (p. 188) 296.23 (F32.2) 296.33 (F33.2)

With psychotic features** (p. 186) 296.24 (F32.3) 296.34 (F33.3)

In partial remission (p. 188) 296.25 (F32.4) 296.35 (F33.41)

In full remission (p. 188) 296.26 (F32.5) 296.36 (F33.42)

Unspecified 296.20 (F32.9) 296.30 (F33.9)

*For an episode to be considered recurrent, there must be an interval of at least 2 consecutive months

between separate episodes in which criteria are not met for a major depressive episode. The definitions of specifiers are found on the indicated pages.

**If psychotic features are present, code the "with psychotic features" specifier irrespective of episode severity.

In recording the name of a diagnosis, terms should be listed in the following order: major

depressive disorder, single or recurrent episode, severity/psychotic/remission specifiers,

followed by as many of the following specifiers without codes that apply to the current

episode.

Specify:

With anxious distress (p. 184)

With mixed features (pp. 184-185)

With melancholic features (p. 185)

With atypical features (pp. 185-186)

With mood-congruent psychotic features (p. 186)

With mood-incongruent psychotic features (p. 186)

With catatonia (p. 186). Coding note: Use additional code 293.89 (F06.1).

With péripartum onset (pp. 186-187)

With seasonal pattern (recurrent episode only) (pp. 187-188)

Diagnostic Features

The criterion symptoms for major depressive disorder must be present nearly every day to

be considered present, with the exception of weight change and suicidal ideation. Depressed mood must be present for most of the day, in addition to being present nearly every day. Often insomnia or fatigue is the presenting complaint, and failure to probe for

accompanying depressive symptoms will result in underdiagnosis. Sadness may be denied at first but may be elicited through interview or inferred from facial expression and

demeanor. With individuals who focus on a somatic complaint, clinicians should determine whether the distress from that complaint is associated with specific depressive

symptoms. Fatigue and sleep disturbance are present in a high proportion of cases; psychomotor disturbances are much less common but are indicative of greater overall severity, as is the presence of delusional or near-delusional guilt.

The essential feature of a major depressive episode is a period of at least 2 weeks during

w^hich there is either depressed mood or the loss of interest or pleasure in nearly all activities (Criterion A). In children and adolescents, the mood may be irritable rather than sad.

The individual must also experience at least four additional symptoms drawn from a list

that includes changes in appetite or weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation or suicide plans or attempts. To

count toward a major depressive episode, a symptom must either be newly present or must

have clearly worsened compared with the person's pre-episode status. The symptoms

must persist for most of the day, nearly every day, for at least 2 consecutive weeks. The episode must be accompanied by clinically significant distress or impairment in social, occupational, or other important areas of functioning. For some individuals with milder

episodes, functioning may appear to be normal but requires markedly increased effort.

The mood in a major depressive episode is often described by the person as depressed,

sad, hopeless, discouraged, or "down in the dumps" (Criterion Al). In some cases, sadness

may be denied at first but may subsequently be elicited by interview (e.g., by pointing out

that the individual looks as if he or she is about to cry). In some individuals who complain

of feeling "blah," having no feelings, or feeling anxious, the presence of a depressed mood

can be inferred from the person's facial expression and demeanor. Some individuals emphasize somatic complaints (e.g., bodily aches and pains) rather than reporting feelings of

sadness. Many individuals report or exhibit increased irritability (e.g., persistent anger, a

tendency to respond to events with angry outbursts or blaming others, an exaggerated

sense of frustration over minor matters). In children and adolescents, an irritable or cranky

mood may develop rather than a sad or dejected mood. This presentation should be differentiated from a pattern of irritability when frustrated.

Loss of interest or pleasure is nearly always present, at least to some degree. Individuals may report feeling less interested in hobbies, "not caring anymore," or not feeling any

enjoyment in activities that were previously considered pleasurable (Criterion A2). Family

members often notice social withdrawal or neglect of pleasurable avocations (e.g., a formerly avid golfer no longer plays, a child who used to enjoy soccer finds excuses not to

practice). In some individuals, there is a significant reduction from previous levels of sexual interest or desire.

Appetite change may involve either a reduction or increase. Some depressed individuals report that they have to force themselves to eat. Others may eat more and may crave

specific foods (e.g., sweets or other carbohydrates). When appetite changes are severe (in

either direction), there may be a significant loss or gain in weight, or, in children, a failure

to make expected weight gains may be noted (Criterion A3).

Sleep disturbance may take the form of either difficulty sleeping or sleeping excessively (Criterion A4). When insomnia is present, it typically takes the form of middle insonrmia (i.e., waking up during the night and then having difficulty returning to sleep) or

terminal insomnia (i.e., waking too early and being unable to return to sleep). Initial insomnia (i.e., difficulty falling asleep) may also occur. Individuals who present with oversleeping (hypersomnia) may experience prolonged sleep episodes at night or increased

daytime sleep. Sometimes the reason that the individual seeks treatment is for the disturbed sleep.

Psychomotor changes include agitation (e.g., the inability to sit still, pacing, handwringing; or pulling or rubbing of the skin, clothing, or other objects) or retardation (e.g.,

slowed speech, thinking, and body movements; increased pauses before answering;

speech that is decreased in volume, inflection, amount, or variety of content, or muteness)

(Criterion A5). The psychomotor agitation or retardation must be severe enough to be observable by others and not represent merely subjective feelings.

Decreased energy, tiredness, and fatigue are common (Criterion A6). A person may report sustained fatigue without physical exertion. Even the smallest tasks seem to require

substantial effort. The efficiency with which tasks are accomplished may be reduced. For

example, an individual may complain that washing and dressing in the morning are exhausting and take twice as long as usual.

The sense of worthlessness or guilt associated with a major depressive episode may include unrealistic negative evaluations of one's worth or guilty preoccupations or ruminations over minor past failings (Criterion A7). Such individuals often misinterpret neutral

or trivial day-to-day events as evidence of personal defects and have an exaggerated sense

of responsibility for untoward events. The sense of worthlessness or guilt may be of delusional proportions (e.g., an individual who is convinced that he or she is personally responsible for world poverty). Blaming oneself for being sick and for failing to meet

occupational or inteφersonal responsibilities as a result of the depression is very common

and, unless delusional, is not considered sufficient to meet this criterion.

Many individuals report impaired ability to think, concentrate, or make even minor

decisions (Criterion A8). They may appear easily distracted or complain of memory difficulties. Those engaged in cognitively demanding pursuits are often unable to function. In

children, a precipitous drop in grades may reflect poor concentration. In elderly individuals, memory difficulties may be the chief complaint and may be mistaken for early signs

of a dementia (''pseudodementia"). When the major depressive episode is successfully

treated, the memory problems often fully abate. However, in some individuals, particularly elderly persons, a major depressive episode may sometimes be the initial presentation of an irreversible dementia.

Thoughts of death, suicidal ideation, or suicide attempts (Criterion A9) are common.

They may range from a passive wish not to awaken in the morning or a belief that others

would be better off if the individual were dead, to transient but recurrent thoughts of committing suicide, to a specific suicide plan. More severely suicidal individuals may have put

their affairs in order (e.g., updated wills, settled debts), acquired needed materials (e.g., a

rope or a gun), and chosen a location and time to accomplish the suicide. Motivations for

suicide may include a desire to give up in the face of perceived insurmountable obstacles,

an intense wish to end what is perceived as an unending and excruciatingly painful emotional state, an inability to foresee any enjoyment in life, or the wish to not be a burden to

others. The resolution of such thinking may be a more meaningful measure of diminished

suicide risk than denial of further plans for suicide.

The evaluation of the symptoms of a major depressive episode is especially difficult

when they occur in an individual who also has a general medical condition (e.g., cancer,

stroke, myocardial infarction, diabetes, pregnancy). Some of the criterion signs and symptoms of a major depressive episode are identical to those of general medical conditions

(e.g., weight loss with untreated diabetes; fatigue with cancer; hypersomnia early in pregnancy; insonmia later in pregnancy or the postpartum). Such symptoms count toward a

major depressive diagnosis except when they are clearly and fully attributable to a general

medical condition. Nonvegetative symptoms of dysphoria, anhedonia, guilt or worthlessness, impaired concentration or indecision, and suicidal thoughts should be assessed with

particular care in such cases. Definitions of major depressive episodes that have been modified to include only these nonvegetative symptoms appear to identify nearly the same individuals as do the full criteria.

Associated Features Supporting Diagnosis

Major depressive disorder is associated with high mortality, much of which is accounted

for by suicide; however, it is not the only cause. For example, depressed individuals admitted to nursing homes have a markedly increased likelihood of death in the first year. Individuals frequently present with tearfulness, irritability, brooding, obsessive rumination,

anxiety, phobias, excessive worry over physical health, and complaints of pain (e.g., headaches; joint, abdominal, or other pains). In children, separation anxiety may occur.

Although an extensive literature exists describing neuroanatomical, neuroendocrinological, and neurophysiological correlates of major depressive disorder, no laboratory test

has yielded results of sufficient sensitivity and specificity to be used as a diagnostic tool for

this disorder. Until recently, hypothalamic-pituitary-adrenal axis hyperactivity had been

the most extensively investigated abnormality associated v^ith major depressive episodes,

and it appears to be associated with melancholia, psychotic features, and risks for eventual

suicide. Molecular studies have also implicated peripheral factors, including genetic variants in neurotrophic factors and pro-inflammatory cytokines. Additionally, functional

magnetic resonance imaging studies provide evidence for functional abnormalities in specific neural systems supporting emotion processing, reward seeking, and emotion regulation in adults with major depression.

Prevalence

Twelve-month prevalence of major depressive disorder in the United States is approximately

7%, with marked differences by age group such that the prevalence in 18- to 29-year-old individuals is threefold higher than the prevalence in individuals age 60 years or older. Females experience 1.5- to 3-fold higher rates than males beginning in early adolescence.

Development and Course

Major depressive disorder may first appear at any age, but the likelihood of onset increases markedly with puberty. In the United States, incidence appears to peak in the 20s;

however, first onset in late life is not uncommon.

The course of major depressive disorder is quite variable, such that some individuals

rarely, if ever, experience remission (a period of 2 or more months with no symptoms, or

only one or two symptoms to no more than a mild degree), while others experience many

years with few or no symptoms between discrete episodes. It is important to distinguish

individuals who present for treatment during an exacerbation of a chronic depressive illness from those whose symptoms developed recently. Chronicity of depressive symptoms

substantially increases the likelihood of underlying personality, anxiety, and substance

use disorders and decreases the likelihood that treatment will be followed by full symptom resolution. It is therefore useful to ask individuals presenting with depressive symptoms to identify the last period of at least 2 months during which they were entirely free of

depressive symptoms.

Recovery typically begins within 3 months of onset for two in five individuals with major depression and within 1 year for four in five individuals. Recency of onset is a strong

determinant of the likelihood of near-term recovery, and many individuals who have been

depressed only for several months can be expected to recover spontaneously. Features associated with lower recovery rates, other than current episode duration, include psychotic

features, prominent anxiety, personality disorders, and symptom severity.

The risk of recurrence becomes progessively lower over time as the duration of remission increases. The risk is higher in individuals whose preceding episode was severe,

in younger individuals, and in individuals who have already experienced multiple episodes. The persistence of even mild depressive symptoms during remission is a powerful

predictor of recurrence.

Many bipolar illnesses begin with one or more depressive episodes, and a substantial

proportion of individuals who initially appear to have major depressive disorder will

prove, in time, to instead have a bipolar disorder. This is more likely in individuals with

onset of the illness in adolescence, those with psychotic features, and those with a family

history of bipolar illness. The presence of a "'with mixed features" specifier also increases

the risk for future manic or hypomanie diagnosis. Major depressive disorder, particularly

with psychotic features, may also transition into schizophrenia, a change that is much

more frequent than the reverse.

Despite consistent differences between genders in prevalence rates for depressive disorders, there appear to be no clear differences by gender in phenomenology, course, or treatment response. Similarly, there are no clear effects of current age on the course or treatment

response of major depressive disorder. Some symptom differences exist, though, such that

hypersomnia and hyperphagia are more likely in younger individuals, and melancholic

symptoms, particularly psychomotor disturbances, are more common in older individuals.

The likelihood of suicide attempts lessens in middle and late life, although the risk of completed suicide does not. Depressions with earlier ages at onset are more familial and more

likely to involve personality disturbances. The course of major depressive disorder within

individuals does not generally change with aging. Mean times to recovery appear to be stable over long periods, and the likelihood of being in an episode does not generally increase

or decrease with time.

Risk and Prognostic Factors

Temperamental. Neuroticism (negative affectivity) is a well-established risk factor for the

onset of major depressive disorder, and high levels appear to render individuals more likely

to develop depressive episodes in response to stressful life events.

Environmental. Adverse childhood experiences, particularly when there are multiple

experiences of diverse types, constitute a set of potent risk factors for major depressive disorder. Stressful life events are well recognized as précipitants of major depressive episodes, but the presence or absence of adverse life events near the onset of episodes does

not appear to provide a useful guide to prognosis or treatment selection.

Genetic and physiological. First-degree family members of individuals with major depressive disorder have a risk for major depressive disorder two- to fourfold higher than

that of the general population. Relative risks appear to be higher for early-onset and recurrent forms. Heritability is approximately 40%, and the personality trait neuroticism accounts for a substantial portion of this genetic liability.

Course modifiers. Essentially all major nonmood disorders increase the risk of an individual developing depression. Major depressive episodes that develop against the background of another disorder often follow a more refractory course. Substance use, anxiety,

and borderline personality disorders are among the most common of these, and the presenting depressive symptoms may obscure and delay their recognition. However, sustained clinical improvement in depressive symptoms may depend on the appropriate

treatment of underlying illnesses. Chronic or disabling medical conditions also increase

risks for major depressive episodes. Such prevalent illnesses as diabetes, morbid obesity,

and cardiovascular disease are often complicated by depressive episodes, and these episodes are more likely to become chronic than are depressive episodes in medically healthy

individuals.

Cuiture-Reiated Diagnostic issues

Surveys of major depressive disorder across diverse cultures have shown sevenfold differences in 12-month prevalence rates but much more consistency in female-to-male raho,

mean ages at onset, and the degree to which presence of the disorder raises the likelihood

of comorbid substance abuse. While these findings suggest substantial cultural differences

in the expression of major depressive disorder, they do not permit simple linkages between particular cultures and the likelihood of specific symptoms. Rather, clinicians

should be aware that in most countries the majority of cases of depression go unrecognized in primary care settings and that in many cultures, somatic symptoms are very likely

to constitute the presenting complaint. Among the Criterion A symptoms, insomnia and

loss of energy are the most uniformly reported.

Gender-Related Diagnostic issues

Although the möst reproducible finding in the epidemiology of major depressive disorder

has been a higher prevalence in females, there are no clear differences between genders in

symptoms, course, treatment response, or functional consequences. In w^omen, the risk for

suicide attempts is higher, and the risk for suicide completion is lower. The disparity in

suicide rate by gender is not as great among those with depressive disorders as it is in the

population as a whole.

Suicide Risic

The possibility of suicidal behavior exists at all times during major depressive episodes.

The most consistently described risk factor is a past history of suicide attempts or threats,

but it should be remembered that most completed suicides are not preceded by unsuccessful attempts. Other features associated with an increased risk for completed suicide

include male sex, being single or living alone, and having prominent feelings of hopelessness. The presence of borderline personality disorder markedly increases risk for future

suicide attempts.

Functional Consequences of

iVlajor Depressive Disorder

Many of the functional consequences of major depressive disorder derive from individual

symptoms. Impairment can be very mild, such that many of those who interact with the affected individual are unaware of depressive symptoms. Impairment may, however, range

to complete incapacity such that the depressed individual is unable to attend to basic selfcare needs or is mute or catatonic. Among individuals seen in general medical settings,

those with major depressive disorder have more pain and physical illness and greater decreases in physical, social, and role functioning.

Differential Diagnosis

Manic episodes with irritable mood or mixed episodes. Major depressive episodes

with prominent irritable mood may be difficult to distinguish from manic episodes with

irritable mood or from mixed episodes. This distinction requires a careful clinical evaluation of the presence of manic symptoms.

Mood disorder due to another medical condition. A major depressive episode is the

appropriate diagnosis if the mood disturbance is not judged, based on individual history,

physical examination, and laboratory findings, to be the direct pathophysiological consequence of a specific medical condition (e.g., multiple sclerosis, stroke, hypothyroidism).

Substance/medication-induced depressive or bipolar disorder. This disorder is distinguished from major depressive disorder by the fact that a substance (e.g., a drug of abuse,

a medication, a toxin) appears to be etiologically related to the mood disturbance. For example, depressed mood that occurs only in the context of withdrawal from cocaine would

be diagnosed as cocaine-induced depressive disorder.

Attention-deficit/hyperactivity disorder. Distractibility and low frustration tolerance

can occur in both attention-deficit/ hyperactivity disorder and a major depressive episode; if the criteria are met for both, attention-deficit/hyperactivity disorder may be diagnosed in addition to the mood disorder. However, the clinician must be cautious not to

overdiagnose a major depressive episode in children with attention-deficit/hyperactivity

disorder whose disturbance in mood is characterized by irritability rather than by sadness

or loss of interest.

Adjustment disorder with depressed mood. A major depressive episode that occurs in

response to a psychosocial stressor is distinguished from adjustment disorder w^ith depressed mood by the fact that the full criteria for a major depressive episode are not met in

adjustment disorder.

Sadness. Finally, periods of sadness are inherent aspects of the human experience.

These periods should not be diagnosed as a major depressive episode unless criteria are

met for severity (i.e., five out of nine symptoms), duration (i.e., most of the day, nearly every day for at least 2 w^eeks), and clinically significant distress or impairment. The diagnosis other specified depressive disorder may be appropriate for presentations of depressed

mood wiih clinically significant impairment that do not meet criteria for duration or severity.

Comorbidity

Other disorders with which major depressive disorder frequently co-occurs are substancerelated disorders, panic disorder, obsessive-compulsive disorder, anorexia nervosa, bulimia nervosa, and borderline personality disorder.

Persistent Depressive Disorder (Dysthymia)

Diagnostic Criteria 300.4 (F34.1)

This disorder represents a consolidation of DSM-lV-defined chronic major depressive disorder and dysthymic disorder.

A. Depressed mood for most of the day, for more days than not, as indicated by either

subjective account or observation by others, for at least 2 years.

Note: In children and adolescents, mood can be irritable and duration must be at least

1 year.

B. Presence, while depressed, of two (or more) of the following:

1. Poor appetite or overeating.

2. Insomnia or hypersomnia.

3. Low energy or fatigue.

4. Low self-esteem.

5. Poor concentration or difficulty making decisions.

6. Feelings of hopelessness.

C. During the 2-year period (1 year for children or adolescents) of the disturbance, the individual has never been without the symptoms in Criteria A and B for more than 2 months at a

time.

D. Criteria for a major depressive disorder may be continuously present for 2 years.

E. There has never been a manic episode or a hypomanie episode, and criteria have

never been met for cyclothymic disorder.

F. The disturbance is not better explained by a persistent schizoaffective disorder,

schizophrenia, delusional disorder, or other specified or unspecified schizophrenia

spectrum and other psychotic disorder.

G. The symptoms are not attributable to the physiological effects of a substance (e.g., a

drug of abuse, a medication) or another medical condition (e.g. hypothyroidism).

H. The symptoms cause clinically significant distress or impairment in social, occupational,

or other important areas of functioning.

Note: Because the criteria for a major depressive episode include four symptoms that are

absent from the symptom list for persistent depressive disorder (dysthymia), a very limited

number of individuals will have depressive symptoms that have persisted longer than 2 years

but will not mee| criteria for persistent depressive disorder. If full criteria for a major depressive episode have been met at some point during the current episode of illness, they

should be given a diagnosis of major depressive disorder. Othenwise, a diagnosis of other

specified depressive disorder or unspecified depressive disorder is warranted.

Specify if:

With anxious distress (p. 184)

With mixed features (pp. 184-185)

With melancholic features (p. 185)

With atypical features (pp. 185-186)

With mood-congruent psychotic features (p. 186)

With mood-incongruent psychotic features (p. 186)

With péripartum onset (pp. 186-187)

Specify if:

In partial remission (p. 188)

In full remission (p. 188)

Specify if:

Early onset: If onset is before age 21 years.

Late onset: If onset is at age 21 years or older.

Specify if (for most recent 2 years of persistent depressive disorder):

With pure dysthymic syndrome: Full criteria for a major depressive episode have not

been met in at least the preceding 2 years.

With persistent major depressive episode: Full criteria for a major depressive episode have been met throughout the preceding 2-year period.

With intermittent major depressive episodes, with current episode: Full criteria for

a major depressive episode are currently met, but there have been periods of at least

8 weeks in at least the preceding 2 years with symptoms below the threshold for a full

major depressive episode.

With intermittent major depressive episodes, without current episode: Full criteria for a major depressive episode are not currently met, but there has been one or

more major depressive episodes in at least the preceding 2 years.

Specify current severity:

Mild (p. 188)

Moderate (p. 188)

Severe (p. 188)

Diagnostic Features

The essential feature of persistent depressive disorder (dysthymia) is a depressed mood

that occurs for most of the day, for more days than not, for at least 2 years, or at least 1 year

for children and adolescents (Criterion A). This disorder represents a consolidation of

DSM-IV-defined chronic major depressive disorder and dysthymic disorder. Major depression may precede persistent depressive disorder, and major depressive episodes may

occur during persistent depressive disorder. Individuals whose symptoms meet major depressive disorder criteria for 2 years should be given a diagnosis of persistent depressive

disorder as well as major depressive disorder.

Individuals with persistent depressive disorder describe their mood as sad or "down

in the dumps." During periods of depressed mood, at least two of the six symptoms from

Criterion B are present. Because these symptoms have become a part of the individual's

day-to-day experience, particularly in the case of early onset (e.g., "I've always been this

way"), they may not be reported unless the individual is directly prompted. E>uring the 2-year

period (1 year for children or adolescents), any symptom-free intervals last no longer than

2 months (Criterion C).

Prevalence

Persistent depressive disorder is effectively an amalgam of DSM-IV dysthymic disorder and

chronic major depressive episode. The 12-month prevalence in the United States is approximately 0.5% for persistent depressive disorder and 1.5% for chronic major depressive disorder.

Development and Course

Persistent depressive disorder often has an early and insidious onset (i.e., in childhood,

adolescence, or early adult life) and, by definition, a chronic course. Among individuals

with both persistent depressive disorder and borderline personality disorder, the covariance of the corresponding features over time suggests the operation of a common mechanism. Early onset (i.e., before age 21 years) is associated with a higher likelihood of

comorbid personality disorders and substance use disorders.

When symptoms rise to the level of a major depressive episode, they are likely to subsequently revert to a lower level. However, depressive symptoms are much less likely to

resolve in a given period of time in the context of persistent depressive disorder than they

are in a major depressive episode.

Risk and Prognostic Factors

Temperamental. Factors predictive of poorer long-term outcome include higher levels

of neuroticism (negative affectivity), greater symptom severity, poorer global functioning,

and presence of anxiety disorders or conduct disorder.

Environmental. Childhood risk factors include parental loss or separation.

Genetic and physiological. There are no clear differences in illness development, course,

or family history between DSM-IV dysthymic disorder and chronic major depressive disorder. Earlier findings pertaining to either disorder are therefore likely to apply to persistent depressive disorder. It is thus likely that individuals with persistent depressive

disorder will have a higher proportion of first-degree relatives with persistent depressive

disorder than do individuals with major depressive disorder, and more depressive disorders in general.

A number of brain regions (e.g., prefrontal cortex, anterior cingulate, amygdala, hippocampus) have been implicated in persistent depressive disorder. Possible polysomnographic abnormalities exist as well.

Functional Consequences of

Persistent Depressive Disorder

The degree to which persistent depressive disorder impacts social and occupational functioning is likely to vary widely, but effects can be as great as or greater than those of major

depressive disorder.

Differential Diagnosis

Major depressive disorder. If there is a depressed mood plus two or more symptoms

meeting criteria for a persistent depressive episode for 2 years or more, then the diagnosis of

persistent depressive disorder is made. The diagnosis depends on the 2-year duration,

which distinguishes it from episodes of depression that do not last 2 years. If the symptom

criteria are sufficient for a diagnosis of a major depressive episode at any time during this period, then the diagnosis of major depression should be noted, but it is coded not as a separate

diagnosis but rather as a specifier with the diagnosis of persistent depressive disorder. If the

individual's symptoms currently meet full criteria for a major depressive episode, then the

specifier of "with intermittent major depressive episodes, with current episode" would be

made. If the major depressive episode has persisted for at least a 2-year duration and remains present, then the specifier "with persistent major depressive episode" is used. When

full major depressive episode criteria are not currently met but there has been at least one

previous episode of major depression in the context of at least 2 years of persistent depressive symptoms, then the specifier of "with intermittent major depressive episodes, without

current episode" is used. If the individual has not experienced an episode of major depression in the last 2 years, then the specifier "with pure dysthymic syndrome" is used.

Psychotic disorders. Depressive symptoms are a common associated feature of chronic

psychotic disorders (e.g., schizoaffective disorder, schizophrenia, delusional disorder). A

separate diagnosis of persistent depressive disorder is not made if the symptoms occur

only during the course of the psychotic disorder (including residual phases).

Depressive or bipolar and related disorder due to another medical condition. Persistent

depressive disorder must be distinguished from a depressive or bipolar and related disorder due to another medical condition. The diagnosis is depressive or bipolar and related

disorder due to another medical condition if the mood disturbance is judged, based on history, physical examination, or laboratory findings, to be attributable to the direct pathophysiological effects of a specific, usually chronic, medical condition (e.g., multiple

sclerosis). If it is judged that the depressive symptoms are not attributable to the physiological effects of another medical condition, then the primary mental disorder (e.g., persistent

depressive disorder) is recorded, and the medical condition is noted as a concomitant medical condition (e.g., diabetes mellitus).

Substance/medication-induced depressive or bipolar disorder. A substance/medication-induced depressive or bipolar and related disorder is distinguished from persistent depressive disorder when a substance (e.g., a drug of abuse, a medication, a toxin) is

judged to be etiologically related to the mood disturbance.

Personality disorders. Often, there is evidence of a coexisting personality disturbance.

When an individual's presentation meets the criteria for both persistent depressive disorder and a personality disorder, both diagnoses are given.

Comorbidity

In comparison to individuals with major depressive disorder, those with persistent depressive disorder are at higher risk for psychiatric comorbidity in general, and for anxiety

disorders and substance use disorders in particular. Early-onset persistent depressive disorder is strongly associated with DSM-IV Cluster B and C personality disorders.

Premenstrual Dysphoric Disorder

Diagnostic Criteria 625.4 (N94.3)

A. In the majority of menstrual cycles, at least five symptoms must be present in the final

week before the onset of menses, start to improve within a few days after the onset of

menses, and become minimal or absent in the week postmenses.

B. One (or more) of the following symptoms must be present:

1. Marked affective lability (e.g., mood swings: feeling suddenly sad or tearful, or increased sensitivity to rejection).

2. Marked irritability or anger or increased interpersonal conflicts.

3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.

4. Marked anxiety, tension, and/or feelings of being keyed up or on edge.

C. One (or more) of the following symptoms must additionally be present, to reach a total

of five symptoms when combined with symptoms from Criterion B above.

1. Decreased interest in usual activities (e.g., work, school, friends, hobbies).

2. Subjective difficulty in concentration.

3. Lethargy, easy fatigability, or marked lack of energy.

4. Marked change in appetite; overeating; or specific food cravings.

5. Hypersomnia or insomnia.

6. A sense of being ovenwhelmed or out of control.

7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a

sensation of “bloating,” or weight gain.

Note: The symptoms in Criteria A-C must have been met for most menstrual cycles that

occurred in the preceding year.

D. The symptoms are associated with clinically significant distress or interference with

work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).

E. The disturbance is not merely an exacerbation of the symptoms of another disorder,

such as major depressive disorder, panic disorder, persistent depressive disorder

(dysthymia), or a personality disorder (although it may co-occur with any of these disorders).

F. Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.)

G. The symptoms are not attributable to the physiological effects of a substance (e.g., a

drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).

Recording Procedures

If symptoms have not been confirmed by prospective daily ratings of at least two symptomatic cycles, "provisional" should be noted after the name of the diagnosis (i.e., "premenstrual dysphoric disorder, provisional").

Diagnostic Features

The essential features of premenstrual dysphoric disorder are the expression of mood lability, irritability, dysphoria, and anxiety symptoms that occur repeatedly during the premenstrual phase of the cycle and remit around the onset of menses or shortly thereafter.

These symptoms may be accompanied by behavioral and physical symptoms. Symptoms

must have occurred in most of the menstrual cycles during the past year and must have an

adverse effect on work or social functioning. The intensity and/or expressivity of the accompanying symptoms may be closely related to social and cultural background characteristics of the affected female, family perspectives, and more specific factors such as

religious beliefs, social tolerance, and female gender role issues.

Typically, symptoms peak around the time of the onset of menses. Although it is not

uncommon for symptoms to linger into the first few days of menses, the individual must

have a symptom-free period in the follicular phase after the menstrual period begins.

While the core symptoms include mood and anxiety symptoms, behavioral and somatic

symptoms commonly also occur. However, the presence of physical and/or behavioral

symptoms in the absence of mood and/or anxious symptoms is not sufficient for a diag­

nosis. Symptoms are of comparable severity (but not duration) to those of another mental

disorder, such a^ a major depressive episode or generalized anxiety disorder. In order to

confirm a provisional diagnosis, daily prospective symptom ratings are required for at

least two symptomatic cycles.

Associated Features Supporting Diagnosis

Delusions and hallucinations have been described in the late luteal phase of the menstrual

cycle but are rare. The premenstrual phase has been considered by some to be a risk period

for suicide.

Prevalence

Twelve-month prevalence of premenstrual dysphoric disorder is between 1.8% and 5.8%

of menstruating women. Estimates are substantially inflated if they are based on retrospective reports rather than prospective daily ratings. However, estimated prevalence

based on a daily record of symptoms for 1-2 months may be less representative, as individuals with the most severe symptoms may be unable to sustain the rating process. The

most rigorous estimate of premenstrual dysphoric disorder is 1.8% for women whose

symptoms meet the full criteria without functional impairment and 1.3% for women

whose symptoms meet the current criteria with functional impairment and without co-occurring symptoms from another mental disorder.

Development and Course

Onset of premenstrual dysphoric disorder can occur at any point after menarche. Incidence of new cases over a 40-month follow-up period is 2.5% (95% confidence interval =

1.7-3.7). Anecdotally, many individuals, as they approach menopause, report that symptoms worsen. Symptoms cease after menopause, although cyclical hormone replacement

can trigger the re-expression of symptoms.

Risk and Prognostic Factors

Environmental. Environmental factors associated with the expression of premenstrual

dysphoric disorder include stress, history of interpersonal trauma, seasonal changes, and

sociocultural aspects of female sexual behavior in general, and female gender role in particular.

Genetic and physiological. Heritability of premenstrual dysphoric disorder is unknown.

However, for premenstrual symptoms, estimates for heritability range between 30% and

80%, with the most stable component of premenstrual symptoms estimated to be about

50% heritable.

Course modifiers. Women who use oral contraceptives may have fewer premenstrual

complaints than do women who do not use oral contraceptives.

Culture-Related Diagnostic Issues

Premenstrual dysphoric disorder is not a culture-bound syndrome and has been observed

in individuals in the United States, Europe, India, and Asia. It is unclear as to whether rates

differ by race. Nevertheless, frequency, intensity, and expressivity of symptoms and helpseeking patterns may be significantly influenced by cultural factors.

Diagnostic Markers

As indicated earlier, the diagnosis of premenstrual dysphoric disorder is appropriately

confirmed by 2 months of prospective symptom ratings. A number of scales, including the

Daily Rating of Severity of Problems and the Visual Analogue Scales for Premenstrual

Mood Symptoms, have undergone validation and are commonly used in clinical trials for

premenstrual dysphoric disorder. The Premenstrual Tension Syndrome Rating Scale has a

self-report and an observer version, both of v^hich have been validated and used widely to

measure illness severity in women who have premenstrual dysphoric disorder.

Functional Consequences of

Premenstrual Dysphoric Disorder

Symptoms must be associated with clinically meaningful distress and/or an obvious and

marked impairment in the ability to function socially or occupationally in the week prior

to menses. Impairment in social functioning may be manifested by marital discord and

problems with children, other family members, or friends. Chronic marital or job problems should not be confused with dysfunction that occurs only in association with premenstrual dysphoric disorder.

Differential Diagnosis

Premenstrual syndrome. Premenstrual syndrome differs from premenstrual dysphoric

disorder in that a minimum of five symptoms is not required, and there is no stipulation of

affective symptoms for individuals who have premenstrual syndrome. This condition

may be more common than premenstrual dysphoric disorder, although the estimated

prevalence of premenstrual syndrome varies. While premenstrual syndrome shares the

feature of symptom expression during the premenstrual phase of the menstrual cycle, it is

generally considered to be less severe than premenstrual dysphoric disorder. The presence of physical or behavioral symptoms in the premenstruum, without the required

affective symptoms, likely meets criteria for premenstrual syndrome and not for premenstrual dysphoric disorder.

Dysmenorrhea. Dysmenorrhea is a syndrome of painful menses, but this is distinct from a

syndrome characterized by affective changes. Moreover, symptoms of dysmenorrhea begin

with the onset of menses, whereas symptoms of premenstrual dysphoric disorder, by definition, begin before the onset of menses, even if they linger into the first few days of menses.

Bipolar disorder, major depressive disorder, and persistent depressive disorder

(dysthymia). Many women with (either naturally occurring or substance/medicationinduced) bipolar or major depressive disorder or persistent depressive disorder believe

that they have premenstrual dysphoric disorder. However, when they chart symptoms,

they realize that the symptoms do not follow a premenstrual pattern. Women with another mental disorder may experience chronic symptoms or intermittent symptoms that

are unrelated to menstrual cycle phase. However, because the onset of menses constitutes

a memorable event, they may report that symptoms occur only during the premenstruum

or that symptoms worsen premenstrually. This is one of the rationales for the requirement

that symptoms be confirmed by daily prospective ratings. The process of differential diagnosis, particularly if the clinician relies on retrospective symptoms only, is made more

difficult because of the overlap between symptoms of premenstrual dysphoric disorder

and some other diagnoses. The overlap of symptoms is particularly salient for differentiating premenstrual dysphoric disorder from major depressive episodes, persistent depressive disorder, bipolar disorders, and borderline personality disorder. However, the

rate of personality disorders is no higher in individuals with premenstrual dysphoric disorder than in those without the disorder.

Use of hormonal treatments. Some women who present with moderate to severe premenstrual symptoms may be using hormonal treatments, including hormonal contraceptives. If such symptoms occur after initiation of exogenous hormone use, the symptoms

may be due to the use of hormones rather than to the underlying condition of premenstrual dysphoriq disorder. If the woman stops hormones and the symptoms disappear,

this is consistent with substance/medication-induced depressive disorder.

Comorbidity

A major depressive episode is the most frequently reported previous disorder in individuals

presenting with premenstrual dysphoric disorder. A wide range of medical (e.g., migraine,

asthma, allergies, seizure disorders) or other mental disorders (e.g., depressive and bipolar

disorders, anxiety disorders, bulimia nervosa, substance use disorders) may worsen in the

premenstrual phase; however, the absence of a symptom-free period during the postmenstrual interval obviates a diagnosis of premenstrual dysphoric disorder. These conditions

are better considered premenstrual exacerbation of a current mental or medical disorder. Although the diagnosis of premenstrual dysphoric disorder should not be assigned in situations in which an individual only experiences a premenstrual exacerbation of another

mental or physical disorder, it can be considered in addition to the diagnosis of another mental or physical disorder if the individual experiences symptoms and changes in level of functioning that are characteristic of premenstrual dysphoric disorder and markedly different

from the symptoms experienced as part of the ongoing disorder.

Substance/Medication-Induced

Depressive Disorder

Diagnostic Criteria

A. A prominent and persistent disturbance in mood that predominates in the clinical picture and is characterized by depressed mood or markedly diminished interest or pleasure in all, or almost all, activities.

B. There is evidence from the history, physical examination, or laboratory findings of both

(1)and(2):

1. The symptoms in Criterion A developed during or soon after substance intoxication

or withdrawal or after exposure to a medication.

2. The involved substance/medication is capable of producing the symptoms in Criterion A.

C. The disturbance is not better explained by a depressive disorder that is not substance/

medication-induced. Such evidence of an independent depressive disorder could include the following:

The symptoms preceded the onset of the substance/medication use; the symptoms

persist for a substantial period of time (e.g., about 1 month) after the cessation of acute

withdrawal or severe intoxication; or there is other evidence suggesting the existence

of an independent non-substance/medication-induced depressive disorder (e.g., a history of recurrent non-substance/medication-related episodes).

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Note: This diagnosis should be made instead of a diagnosis of substance intoxication or

substance withdrawal only when the symptoms in Criterion A 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/medication]-induced depressive disorders are indicated in the table below. Note that the ICD-10-

CM code depends on wliether 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 substanceinduced depressive disorder, the 4th position character is “1 and the clinician should record

“mild [substance] use disorder” before the substance-induced depressive disorder (e.g.,

“mild cocaine use disorder with cocaine-induced depressive disorder”). If a moderate or severe substance use disorder is comorbid with the substance-induced depressive 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 (e.g., after a onetime heavy use of the substance), then the 4th position character is “9,” and the clinician should

record only the substance-induced depressive disorder.

ICD-10-CM

ICD-9-CM

With use

disorder,

mild

With use

disorder,

moderate

or severe

Without

use

disorder

Alcohol 291.89 F10.14 F10.24 FI 0.94

Phencyclidine 292.84 F16.14 F16.24 F16.94

Other hallucinogen 292.84 F16.14 F16.24 FI 6.94

Inhalant 292.84 F18.14 F18.24 FI 8.94

Opioid 292.84 F11.14 F11.24 F11.94

Sedative, hypnotic, or anxiolytic 292.84 F13.14 FI 3.24 FI 3.94

Amphetamine (or other

stimulant)

292.84 F15.14 FI 5.24 FI 5.94

Cocaine 292.84 F14.14 FI 4.24 FI 4.94

Other (or unknown) substance 292.84 F19.14 F19.24 FI 9.94

Specify if (see Table 1 in the chapter “Substance-Related and Addictive Disorders” for diagnoses associated with substance class):

With onset during intoxication: If criteria are met for intoxication with the substance

and the symptoms develop during intoxication.

With onset during withdrawal: If criteria are met for withdrawal from the substance

and the symptoms develop during, or shortly after, withdrawal.

Recording Procedures

ICD-9-CM. The name of the substance/medication-induced depressive disorder begins

with the specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing

the depressive 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 (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 specification of onset (i.e., onset during intoxication, onset during withdrawal). Unlike the recording procedures for ICD-IO-CM,

which combine the substance-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 qase of depressive symptoms occurring during withdrawal in a man with

a severe cocaine use disorder, the diagnosis is 292.84 cocaine-induced depressive disorder,

with onset during withdrawal. An additional diagnosis of 304.20 severe cocaine use disorder is also given. When more than one substance is judged to play a significant role in

the development of depressive mood symptoms, each should be listed separately (e.g.,

292.84 methylphenidate-induced depressive disorder, with onset during withdrawal;

292.84 dexamethasone-induced depressive disorder, with onset during intoxication).

ICD-10-CM. The name of the substance/medication-induced depressive disorder begins

with the specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing

the depressive 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 (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-induced depressive disorder, followed by the specification of onset (i.e., onset during intoxication, onset

during withdrawal). For example, in the case of depressive symptoms occurring during withdrawal in a man with a severe cocaine use disorder, the diagnosis is F14.24 severe cocaine use

disorder with cocaine-induced depressive disorder, with onset during withdrawal. A separate

diagnosis of the comorbid severe cocaine use disorder is not given. If the substance-induced

depressive disorder 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., F16.94

phencyclidine-induced depressive disorder, with onset during intoxication). When more than

one substance is judged to play a significant role in the development of depressive mood

symptoms, each should be listed separately (e.g., F15.24 severe methylphenidate use disorder

with methylphenidate-induced depressive disorder, with onset during withdrawal; F19.94

dexamethasone-induced depressive disorder, with onset during intoxication).

Diagnostic Features

The diagnostic features of substance/medication-induced depressive disorder include the

symptoms of a depressive disorder, such as major depressive disorder; however, the depressive symptoms are associated with the ingestion, injection, or inhalation of a substance (e.g., drug of abuse, toxin, psychotropic medication, other medication), and the

depressive symptoms persist beyond the expected length of physiological effects, intoxication, or withdrawal period. As evidenced by clinical history, physical examination, or

laboratory findings, the relevant depressive disorder should have developed during or

within 1 month after use of a substance that is capable of producing the depressive disorder (Criterion Bl). In addition, the diagnosis is not better explained by an independent

depressive disorder. Evidence of an independent depressive disorder includes the depressive disorder preceded the onset of ingestion or withdrawal from the substance; the

depressive disorder persists beyond a substantial period of time after the cessation of substance use; or other evidence suggests the existence of an independent non-substance/

medication-induced depressive disorder (Criterion C). This diagnosis should not be made

when symptoms occur exclusively during the course of a delirium (Criterion D). The depressive disorder associated with the substance use, intoxication, or withdrawal must

cause clinically significant distress or impairment in social, occupational, or other important areas of functioning to qualify for this diagnosis (Criterion E).

Some medications (e.g., stimulants, steroids, L-dopa, antibiotics, central nervous

system drugs, dermatological agents, chemotherapeutic drugs, immunological agents)

can induce depressive mood disturbances. Clinical judgment is essential to determine

whether the medication is truly associated with inducing the depressive disorder or

whether a primary depressive disorder happened to have its onset while the person was

receiving the treatment. For example, a depressive episode that developed within the first

several weeks of beginning alpha-methyldopa (an antihypertensive agent) in an individual with no history of major depressive disorder would qualify for the diagnosis of medication-induced depressive disorder. In some cases, a previously established condition

(e.g., major depressive disorder, recurrent) can recur while the individual is coincidentally

taking a medication that has the capacity to cause depressive symptoms (e.g., L-dopa, oral

contraceptives). In such cases, the clinician must make a judgment as to whether the medication is causative in this particular situation.

A substance/medication-induced depressive disorder is distinguished from a primary

depressive disorder by considering the onset, course, and other factors associated with the

substance use. There must be evidence from the history, physical examination, or laboratory findings of substance use, abuse, intoxication, or withdrawal prior to the onset of the

depressive disorder. The withdrawal state for some substances can be relatively protracted, and thus intense depressive symptoms can last for a long period after the cessation

of substance use.

Prevalence

In a nationally representative U.S. adult population, the lifetime prevalence of substance/

medication-induced depressive disorder is 0.26%.

Development and Course

A depressive disorder associated with the use of substance (i.e., alcohol, illicit drugs, or a

prescribed treatment for a mental disorder or another medical condition) must have its onset while the individual is using the substance or during withdrawal, if there is a withdrawal syndrome associated with the substance. Most often, the depressive disorder has

its onset within the first few weeks or 1 month of use of the substance. Once the substance

is discontinued, the depressive symptoms usually remit within days to several weeks, depending on the half-life of the substance/medication and the presence of a withdrawal

syndrome. If symptoms persist 4 weeks beyond the expected time course of withdrawal of

a particular substance/medication, other causes for the depressive mood symptoms

should be considered.

Although there are a few prospective controlled trials examining the association of depressive symptoms with use of a medication, most reports are from postmarketing surveillance studies, retrospective observational studies, or case reports, making evidence of

causality difficult to determine. Substances implicated in medication-induced depressive

disorder, with varying degrees of evidence, include antiviral agents (efavirenz), cardiovascular agents (clonidine, guanethidine, methyldopa, reserpine), retinoic acid derivatives (isotretinoin), antidepressants, anticonvulsants, anti-migraine agents (triptans),

antipsychotics, hormonal agents (corticosteroids, oral contraceptives, gonadotropinreleasing hormone agonists, tamoxifen), smoking cessation agents (varenicline), and immunological agents (interferon). However, other potential substances continue to emerge

as new compounds are synthesized. A history of such substance use may help increase diagnostic certainty.

Risk and Prognostic Factors

Temperamental. Factors that appear to increase the risk of substance/medicationinduced depressive disorder can be conceptualized as pertaining to the specific type of

drug or to a group of individuals with underlying alcohol or drug use disorders. Risk fac­

tors common to all drugs include history of major depressive disorder, history of druginduced depression, and psychosocial stressors.

Environmental, There are also risks factors pertaining to a specific type of medication

(e.g., increased immune activation prior to treatment for hepatitis C associated with interferon-alfa-induced depression); high doses (greater than 80 mg/day prednisone-equivalents) of corticosteroids or high plasma concentrations of efavirenz; and high estrogen/

progesterone content in oral contraceptives.

Course modifiers. In a representative U.S. adult population, compared with individuals

with major depressive disorder who did not have a substance use disorder, individuals

with substance-induced depressive disorder were more likely to be male, to be black, to

have at most a high school diploma, to lack insurance, and to have lower family income.

They were also more likely to report higher family history of substance use disorders and

antisocial behavior, higher 12-month history of stressful life events, and a greater number

of DSM-rV major depressive disorder criteria. They were more likely to report feelings of

worthlessness, insomnia/hypersomnia, and thoughts of death and suicide attempts, but

less likely to report depressed mood and parental loss by death before age 18 years.

Diagnostic iViarlcers

Determination of the substance of use can sometimes be made through laboratory assays

of the suspected substance in the blood or urine to corroborate the diagnosis.

Suicide Risic

Drug-induced or treatment-emergent suicidality represents a marked change in thoughts

and behavior from the person's baseline, is usually temporally associated with initiation of

a substance, and must be distinguished from the underlying primary mental disorders.

In regard to the treatment-emergent suicidality associated with antidepressants, a U.S.

Food and Drug Administration (FDA) advisory committee considered meta-analyses of

99,839 participants enrolled in 372 randomized clinical trials of antidepressants in trials for

mental disorders. The analyses showed that when the data were pooled across all adult

age groups, there was no perceptible increased risk of suicidal behavior or ideation. However, in age-stratified analyses, the risk for patients ages 18-24 years was elevated, albeit

not significantly (odds ratio [OR] = 1.55; 95% confidence interval [Cl] = 0.91-2.70). The

FDA meta-analyses reveal an absolute risk of suicide in patients taking investigational antidepressants of 0.01%. In conclusion, suicide is clearly an extremely rare treatment-emergent phenomenon, but the outcome of suicide was serious enough to prompt the FDA to

issue an expanded black-box warning in 2007 regarding the importance of careful monitoring of treatment-emergent suicidal ideation in patients receiving antidepressants.

Differential Diagnosis

Substance intoxication and withdrawal. Depressive symptoms occur commonly in substance intoxicahon and substance withdrawal, and the diagnosis of the substance-specific

intoxication or withdrawal will usually suffice to categorize the symptom presentation. A

diagnosis of substance-induced depressive disorder should be made instead of a diagnosis of substance intoxication or substance withdrawal when the mood symptoms are

sufficiently severe to warrant independent clinical attention. For example, dysphoric

mood is a characteristic feature of cocaine withdrawal. Substance/medication-induced

depressive disorder should be diagnosed instead of cocaine withdrawal only if the mood

disturbance is substantially more intense or longer lasting than what is usually encountered

with cocaine withdrawal and is sufficiently severe to be a separate focus of attention and

treatment.

Primary depressive disorder. A substance/medication-induced depressive disorder is

distinguished from a primary depressive disorder by the fact that a substance is judged to

be etiologically related to the symptoms, as described earlier (see section "Development

and Course" for this disorder).

Depressive disorder due to another medical condition. Because individuals with other

medical conditions often take medications for those conditions, the clinician must consider the

possibility that the mood symptoms are caused by the physiological consequences of the medical condition rather than the medication, in which case depressive disorder due to another

medical condition is diagnosed. The history often provides Üie primary basis for such a judgment. At times, a change in the treatment for the other medical condition (e.g., medication substitution or discontinuation) may be needed to determine empirically whether the medication

is the causative agent. If the clinician has ascertained that the disturbance is a function of both

another medical condition and substance use or withdrawal, both diagnoses (i.e., depressive

disorder due to another medical condition and substance/medication-induced depressive

disorder) may be given. When there is insufficient evidence to determine whether the depressive symptoms are associated with substance (including a medication) ingestion or withdrawal or with another medical condition or are primary (i.e., not a function of either a

substance or another medical condition), a diagnosis of other specified depressive disorder or

unspecified depressive disorder would be indicated.

Comorbidity

Compared with individuals with major depressive disorder and no comorbid substance

use disorder, those with substance/medication-induced depressive disorder have higher

rates of comorbidity with any DSM-IV mental disorder; are more likely to have specific

DSM-IV disorders of pathological gambling and paranoid, histrionic, and antisocial personality disorders; and are less likely to have persistent depressive disorder (dysthymia).

Compared with individuals with major depressive disorder and a comorbid substance use

disorder, individuals with substance/medication-induced depressive disorder are more

likely to have alcohol use disorder, any other substance use disorder, and histrionic personality disorder; however, they are less likely to have persistent depressive disorder.

Depressive Disorder

Due to Another l\/ledical Condition

Diagnostic Criteria

A. A prominent and persistent period of depressed mood or markedly diminished interest

or pleasure in all, or almost all, activities that predominates in the clinical picture.

B. There is evidence from the history, physical examination, or laboratory findings that the

disturbance is the direct pathophysiological consequence of another medical condition.

C. The disturbance is not better explained by another mental disorder (e.g., adjustment

disorder, with depressed mood, in which the stressor is a serious medical condition).

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Coding note: The ICD-9-CM code for depressive disorder due to another medical condition is 293.83, which is assigned regardless of the specifier. The ICD-10-CM code depends on the specifier (see below).

Specify if:

(F06.31) With depressive features: Full criteria are not met for a major depressive

episode. '

(F06.32) Witli major depressive-iilce episode: Full criteria are met (except Criterion

C) for a major depressive episode.

(F06.34) With mixed features: Symptoms of mania or hypomania are also present but

do not predominate in the clinical picture.

Coding note: Include the name of the other medical condition in the name of the mental disorder (e.g., 293.83 [F06.31] depressive disorder due to hypothyroidism, with depressive features). The other medical condition should also be coded and listed separately immediately

before the depressive disorder due to the medical condition (e.g., 244.9 [E03.9] hypothyroidism; 293.83 [F06.31] depressive disorder due to hypothyroidism, with depressive features).

Diagnostic Features

The essential feature of depressive disorder due to another medical condition is a prominent and persistent period of depressed mood or markedly diminished interest or pleasure in all, or almost all, activities that predominates in the clinical picture (Criterion A)

and that is thought to be related to the direct physiological effects of another medical condition (Criterion B). In determining whether the mood disturbance is due to a general

medical condition, the clinician must first establish the presence of a general medical condition. Further, the clinician must establish that the mood disturbance is etiologically related to the general medical condition through a physiological mechanism. A careful and

comprehensive assessment of multiple factors is necessary to make this judgment. Although there are no infallible guidelines for determining whether the relationship

between the mood disturbance and the general medical condition is etiological, several

considerations provide some guidance in this area. One consideration is the presence of a

temporal association between the onset, exacerbation, or remission of the general medical

condition and that of the mood disturbance. A second consideration is the presence of features that are atypical of primary Mood Disorders (e.g., atypical age at onset or course or

absence of family history). Evidence from the literature that suggests that there can be a direct association between the general medical condition in question and the development

of mood symptoms can provide a useful context in the assessment of a particular situation.

Associated Features Supporting Diagnosis

Etiology (i.e., a causal relationship to another medical condition based on best clinical evidence) is the key variable in depressive disorder due to another medical condition. The

listing of the medical conditions that are said to be able to induce major depression is never

complete, and the clinician's best judgment is the essence of this diagnosis.

There are clear associations, as well as some neuroanatomical correlates, of depression

with stroke, Huntington's disease, Parkinson's disease, and traumatic brain injury. Among

the neuroendocrine conditions most closely associated with depression are Cushing's disease and hypothyroidism. There are numerous other conditions thought to be associated

with depression, such as multiple sclerosis. However, the literature's support for a causal

association is greater with some conditions, such as Parkinson's disease and Huntington's

disease, than with others, for which the differential diagnosis may be adjustment disorder,

with depressed mood.

Deveiopment and Course

Following stroke, the onset of depression appears to be very acute, occurring within 1 day

or a few days of the cerebrovascular accident (CVA) in the largest case series. However, in

some cases, onset of the depression is weeks to months following the CVA. In the largest

series, the duration of the major depressive episode following stroke was 9-11 months on

average. Similarly, in Huntington's disease the depressive state comes quite early in the

course of the illness. With Parkinson's disease and Huntington's disease, it often precedes

the major motor impairments and cognitive impairments associated with each condition.

This is more prominently the case for Huntington's disease, in which depression is considered to be the first neuropsychiatric symptom. There is some observational evidence

that depression is less common as the dementia of Huntington's disease progresses.

Risk and Prognostic Factors

The risk of acute onset of a major depressive disorder following a CVA (within 1 day to a

week of the event) appears to be strongly correlated with lesion location, with greatest risk

associated with left frontal strokes and least risk apparently associated with right frontal

lesions in those individuals who present within days of the stroke. The association with

frontal regions and laterality is not observed in depressive states that occur in the 2-6 months

following stroke.

Gender-Related Diagnostic issues

Gender differences pertain to those associated with the medical condition (e.g., systemic

lupus erythematosus is more common in females; stroke is somewhat more common in

middle-age males compared with females).

Diagnostic iVlarlcers

Diagnostic markers pertain to those associated with the medical condition (e.g., steroid

levels in blood or urine to help corroborate the diagnosis of Cushing's disease, which can

be associated with manic or depressive syndromes).

Suicide Risic

There are no epidemiological studies that provide evidence to differentiate the risk of suicide from a major depressive episode due to another medical condition compared with the

risk from a major depressive episode in general. There are case reports of suicides in

association with major depressive episodes associated with another medical condition.

There is a clear association between serious medical illnesses and suicide, particularly

shortly after onset or diagnosis of the illness. Thus, it would be prudent to assume that the

risk of suicide for major depressive episodes associated with medical conditions is not less

than that for other forms of major depressive episode, and might even be greater.

Functional Consequences of Depressive Disorder

Due to Another iViedicai Condition

Functional consequences pertain to those associated with the medical condition. In general, it is believed, but not established, that a major depressive episode induced by Cushing's disease will not recur if the Cushing's disease is cured or arrested. However, it is also

suggested, but not established, that mood syndromes, including depressive and manic/

hypomanie ones, may be episodic (i.e., recurring) in some individuals with static brain injuries and other central nervous system diseases.

Differential Diagnosis

Depressive disorders not due to another medical condition. Determination of whether

a medical condition accompanying a depressive disorder is causing the disorder depends

on a) the absence of an episode(s) of depressive episodes prior to the onset of the medical

condition, b) the probability that the associated medical condition has a potential to promote or cause a depressive disorder, and c) a course of the depressive symptoms shortly

after the onset oi^ worsening of the medical condition, especially if the depressive symptoms remit near the time that the medical disorder is effectively treated or remits.

Medication-induced depressive disorder. An important caveat is that some medical conditions are treated with medications (e.g., steroids or alpha-interferon) that can induce depressive or manic symptoms. In these cases, clinical judgment, based on all the evidence in hand, is

the best way to try to separate the most likely and/or the most important of two etiological factors (i.e., association with the medical condition vs. a substance-induced syndrome).

Adjustment disorders. It is important to differentiate a depressive episode from an adjustment disorder, as the onset of the medical condition is in itself a life stressor that could

bring on either an adjustment disorder or an episode of major depression. The major differentiating elements are the pervasiveness the depressive picture and the number and

quality of the depressive symptoms that the patient reports or demonstrates on the mental

status examination. The differential diagnosis of the associated medical conditions is relevant but largely beyond the scope of the present manual.

Comorbidity

Conditions comorbid with depressive disorder due to another medical condition are those

associated with the medical conditions of etiological relevance. It has been noted that delirium can occur before or along with depressive symptoms in individuals with a variety

of medical conditions, such as Cushing's disease. The association of anxiety symptoms,

usually generalized symptoms, is common in depressive disorders, regardless of cause.

Other Specified Depressive Disorder

311 (F32.8)

This category applies to presentations in which symptoms characteristic of a depressive

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 depressive disorders diagnostic class. The other specified depressive

disorder category is used in situations in which the clinician chooses to communicate the

specific reason that the presentation does not meet the criteria for any specific depressive

disorder. This is done by recording “other specified depressive disorder” followed by the

specific reason (e.g., “short-duration depressive episode”).

Examples of presentations that can be specified using the “other specified” designation

include the following:

1. Recurrent brief depression: Concurrent presence of depressed mood and at least

four other symptoms of depression for 2-13 days at least once per month (not associated with the menstrual cycle) for at least 12 consecutive months in an individual

whose presentation has never met criteria for any other depressive or bipolar disorder

and does not currently meet active or residual criteria for any psychotic disorder.

2. Short-duration depressive episode (4-13 days): Depressed affect and at least four

of the other eight symptoms of a major depressive episode associated with clinically

significant distress or impairment that persists for more than 4 days, but less than 14 days,

in an individual whose presentation has never met criteria for any other depressive or

bipolar disorder, does not currently meet active or residual criteria for any psychotic disorder, and does not meet criteria for recurrent brief depression.

3. Depressive episode with insufficient symptoms: Depressed affect and at least one

of the other eight symptoms of a major depressive episode associated with clinically

significant distress or impairment tliat persist for at least 2 weeks in an individual

whose presentation has never met criteria for any other depressive or bipolar disorder,

does not currently meet active or residual criteria for any psychotic disorder, and does

not meet criteria for mixed anxiety and depressive disorder symptoms.

Unspecified Depressive Disorder

311 (F32.9)

This category applies to presentations in which symptoms characteristic of a depressive 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 depressive disorders diagnostic class. The unspecified depressive disorder category is

used in situations in which the clinician chooses not to specify the reason that the criteria are

not met for a specific depressive disorder, and includes presentations for which there is insufficient information to make a more specific diagnosis (e.g., in emergency room settings).

Specifiers for Depressive Disorders

Specify if:

With anxious distress: Anxious distress is defined as the presence of at least two of

the following symptoms during the majority of days of a major depressive episode or

persistent depressive disorder (dysthymia):

1. Feeling keyed up or tense.

2. Feeling unusually restless.

3. Difficulty concentrating because of worry.

4. Fear that something awful may happen.

5. Feeling that the individual might lose control of himself or herself.

Specify current severity:

IMild: Two symptoms.

■Moderate: Three symptoms.

■Moderate-severe: Four or five symptoms.

Severe: Four or five symptoms and with motor agitation.

Note: Anxious distress has been noted as a prominent feature of both bipolar and major depressive disorder in both primary care and specialty mental health settings. High

levels of anxiety have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse. As a result, it is clinically useful

to specify accurately the presence and severity levels of anxious distress for treatment

planning and monitoring of response to treatment.

Witli mixed features:

A. At least three of the following manic/hypomanic symptoms are present nearly every

day during the majority of days of a major depressive episode:

1. Elevated, expansive mood.

2. Inflated self-esteem or grandiosity.

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Increase in energy or goal-directed activity (either socially, at work or school, or

sexually).

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