Bipolar disorder in adults: Assessment and diagnosis

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Bipolar disorder in adults: Assessment and diagnosis Authors Trisha Suppes, MD Victoria E Cosgrove, PhD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2013. | This topic last updated: Ago 5, 2013. INTRODUCTION Making the diagnosis of bipolar disorder is often difficult, and following onset of symptoms, many years may elapse until the diagnosis is established [1]. As an example, a self-administered survey in 441 bipolar patients found that 35 percent waited at least 10 years between first seeking treatment and receiving the correct diagnosis [2]. This topic reviews the assessment and diagnosis of bipolar disorder in adults. The clinical features and treatment of bipolar disorder in adults are discussed separately, as are the clinical features and diagnosis of bipolar disorder in children and adolescents, geriatric patients, and patients with rapid cycling (ie, four or more mood episodes in a 12-month period): (See "Bipolar disorder in adults: Clinical features".) (See "Bipolar disorder in adults: Pharmacotherapy for acute depression".) (See "Bipolar disorder in adults: Pharmacotherapy for acute mania, mixed episodes, and hypomania".) (See "Bipolar disorder in adults: Maintenance treatment".) (See "Bipolar disorder in children and adolescents: Epidemiology, pathogenesis, clinical manifestations, and course".) (See "Bipolar disorder in children and adolescents: Assessment and diagnosis".) (See "Geriatric bipolar disorder: Epidemiology, clinical features, assessment, and diagnosis".) (See "Rapid cycling bipolar disorder: Epidemiology, pathogenesis, clinical features, and diagnosis".) ASSESSMENT The initial clinical evaluation of patients with a possible diagnosis of bipolar disorder includes a psychiatric and general medical history, mental status and physical examination, and focused laboratory tests (eg, thyroid stimulating hormone, complete blood count, chemistries, and urine toxicology to screen for substances of abuse) [3-5]. The psychiatric history and mental status examination should assess patients for [6]: Major depression (table 1) Mania (table 2) Hypomania (table 3) Mixed episodes (concurrent major depression and mania) Suicidal thoughts and behavior Risk factors for suicide attempts and deaths (see "Bipolar disorder in adults: Clinical features", section on 'Suicide') Psychotic features (delusions or hallucinations) (see "Bipolar disorder in adults: Clinical features", section on 'Psychosis') Comorbid psychiatric and general medical disorders (see "Bipolar disorder in adults: Clinical features", section on 'Comorbidity') In addition to current symptoms, it is important to ascertain the number, frequency, intensity, and duration of past mood episodes. Interviewing family members of patients with a possible diagnosis of bipolar disorder is often helpful [6-8]. Patients may not be forthcoming about suicidal ideation, plans, and attempts; in addition, patients may present with major Section Editor Paul Keck, MD Deputy Editor David Solomon, MD

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depression and not recall prior episodes of mania or hypomania, especially if these last occurred several years in the past, were marked by irritability rather than euphoria, or consisted of postpartum mood states. Patients who present with mania, hypomania, or psychosis often have poor insight and difficulty providing a history. Additional testing, such as brain imaging or electroencephalography (EEG), is guided by relevant findings in the history and examination [9-11]. Although neuroimaging studies show abnormalities in different areas of the brain, the only indication for imaging is to rule out disorders that may present with mood symptoms (eg, central nervous system mass) [12,13]. Screening instruments Although screening for bipolar disorder is often recommended and there are many available instruments [14-17], it is not known whether screening improves patient outcomes. Studies in unipolar major depression indicate that screening is beneficial only in settings that can provide follow-up to ensure accurate diagnosis and effective treatment. (See "Screening for depression", section on 'Effectiveness of screening'.) It is also not clear that bipolar screening instruments perform well enough to warrant routine use, particularly in psychiatric outpatients [18]. The most widely used and translated measure that screens for a lifetime history of manic or hypomanic episodes is the 15-item Mood Disorder Questionnaire (table 4) [14,19-21]. A pooled analysis of the questionnaires operating characteristics in mood disorder specialty clinics found that across 11 studies (2052 patients with mood disorders), sensitivity was 65 percent, specificity 81 percent, and positive predictive value 69 percent [22]. In three studies of unselected, heterogeneous psychiatric outpatients (N = 943), sensitivity was 65 percent, specificity was 82 percent, and positive predictive value was 39 percent. The sensitivities indicate that the measure fails to identify approximately 33 percent of bipolar patients. In addition, the positive predictive values indicate that among psychiatric patients who screen positive for bipolar disorder, many do not have the disorder. Thus, the questionnaire should not be used as a diagnostic proxy for case finding; patients who screen positive require a diagnostic interview to make the diagnosis. The Mood Disorder Questionnaire appears to be even less useful in screening for bipolar II disorder than bipolar I disorder [14]. A pooled analysis of 12 studies (N = 613 patients) found that the sensitivity for bipolar I disorder was 66 percent, but for bipolar II disorder was only 39 percent [22]. The long-term reliability of the Mood Disorder Questionnaire is also limited. A study found that the ability of the instrument to detect manic and hypomanic episodes after two years had elapsed was poor [23]. In a primary care setting, the sensitivity of the Mood Disorder Questionnaire was fair (58 percent) and specificity excellent (93 percent) [24]. Thus, many bipolar patients were not identified by the instrument. Diagnostic instruments Structured and semi-structured, interviewer-administered, diagnostic instruments are available for diagnosing bipolar disorder but are rarely used in routine clinical practice. A structured instrument enables the interviewer to clarify ambiguous or contradictory responses, and may help differentiate the diagnosis of unipolar major depression (major depressive disorder) from bipolar disorder. However, structured instruments are labor intensive and generally reserved for specialized evaluation, treatment, or research settings. Validated instruments include the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID), Patient Edition [25]. This instrument systematically assesses each criterion for every psychiatric disorder, and has good to excellent reliability and validity that is mostly a function of interviewer training and experience. A reasonable alternative is the Mini-International Neuropsychiatric Interview, which has good psychometric properties and requires less time to administer than the SCID [26]. DIAGNOSIS Diagnosis of bipolar disorder and its subtypes begins by diagnosing the mood episodes that comprise bipolar disorders, and also requires that the clinician exclude other relevant disorders (see 'Mood episodes' below and 'Bipolar disorders' below and 'Differential diagnosis' below). We suggest diagnosing bipolar mood episodes and disorders according to the American Psychiatric Association's Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) [6]. However, a reasonable alternative is the World Health Organization's International Classification of Diseases-10th Revision (ICD-10) [27]. The two sets of criteria are largely the same; however, DSM-IV-TR includes two subtypes of bipolar disorder that are labelled bipolar I disorder and bipolar II disorder, which in ICD-10 are subsumed by the diagnosis bipolar affective disorder.

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Mood episodes Bipolar mood episodes include mania, hypomania, major depression, and mixed episodes (concurrent mania and major depression) [6]. Mania The diagnostic criteria for manic episodes are described in the table (table 2). Mania is characterized by an elevated or irritable mood lasting at least one week (or any duration if hospitalization is necessary) [6]. During the mood disturbance, three (if elated mood predominates) or four (if irritable mood predominates) of the following symptoms must be present: Inflated self-esteem or grandiosity Decreased need for sleep More talkative than usual or pressured speech Flight of ideas (abrupt changes from one topic to another that are based upon understandable associations) or racing thoughts Distractibility Increase in goal-directed activity or psychomotor agitation Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, buying sprees or sexual indiscretions) In addition, the symptoms impair psychosocial functioning, necessitate hospitalization, or are accompanied by psychotic features (eg, delusions or hallucinations), and are not the direct result of a substance or general medical condition. Additional information about the clinical features of mania is presented separately. (See "Bipolar disorder in adults: Clinical features", section on 'Mania'.) Hypomania The diagnostic criteria for hypomanic episodes are described in the table (table 3). Hypomania is characterized by an elevated or irritable mood lasting at least four consecutive days [6]. During the mood disturbance, three (if elated mood predominates) or four (if irritable mood predominates) of the additional symptoms that characterize mania must be present (see 'Mania' above). One review estimated that 5 to 15 percent of patients with hypomania transition to mania [6]. The distinction between hypomanic and manic episodes is based upon the intensity and duration of symptoms. Hypomanic symptoms are generally less severe than manic symptoms, and the diagnosis of hypomania requires at least four days of symptoms, whereas mania requires at least seven days [6]. In addition, psychosocial functioning in hypomania is either mildly impaired or improved, whereas functioning in mania is markedly impaired. Mania frequently includes psychotic features and leads to hospitalization; by definition, hypomania does not. Additional information about the clinical features of hypomania is presented separately. (See "Bipolar disorder in adults: Clinical features", section on 'Hypomania'.) Hypomanic episodes may occur with bipolar I disorder, bipolar II disorder, cyclothymic disorder, or bipolar disorder not otherwise specified (see 'Bipolar disorders' below). Major depression The diagnostic criteria for major depressive episodes are described in the table (table 1). Major depression is characterized by at least five of the following symptoms for at least two weeks; at least one of the symptoms is either dysphoria or anhedonia [6]: Depressed mood most of the day, nearly every day Diminished interest or pleasure in nearly all daily activities, most of the day, nearly every day Significant weight loss or weight gain (eg, 5 percent within a month) Insomnia or hypersomnia nearly every day Psychomotor agitation or retardation nearly every day Fatigue or loss of energy nearly every day Feelings of worthlessness or inappropriate guilt nearly every day Diminished ability to think or concentrate nearly every day Recurrent thoughts of death or suicidal ideation, or a suicide attempt In addition, the symptoms cause significant distress or psychosocial impairment, and are not the direct result of a substance or general medical condition. Additional information about the clinical features of bipolar major depression is presented separately. (See "Bipolar disorder in adults: Clinical features", section on 'Major depression'.)

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Major depressive episodes may occur with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified (see 'Bipolar disorders' below). Mixed episode Mixed episodes are diagnosed when full criteria for a manic (table 2) and major depressive episode (except duration) (table 1) are met concurrently for at least one week. Mixed episodes occur only with bipolar I disorder (see 'Bipolar I disorder' below). Mood disorder specifiers DSM-IV-TR utilizes several terms to increase the diagnostic specificity of bipolar mood episodes (as well as other mood disorder episodes), including [6]: Psychotic features Psychotic features include delusions (false, fixed beliefs) and hallucinations (false sensory perceptions) (see "Overview of psychosis", section on 'Psychosis') Catatonic features Catatonic features are characterized by prominent psychomotor disturbances (see "Catatonia in adults: Epidemiology, clinical features, assessment, and diagnosis") Postpartum onset Postpartum onset refers to onset of mood episodes within four weeks of childbirth (see "Bipolar disorder in postpartum women: Epidemiology, clinical features, assessment, and diagnosis") Bipolar disorders There are four types of bipolar disorders that are described in DSM-IV-TR [6]: Bipolar I disorder Bipolar II disorder Cyclothymic disorder Bipolar disorder not otherwise specified (NOS) Difficulties in diagnosing bipolar disorder may lead clinicians to under diagnose [28-30] or over diagnose [31-33] the disorder. Misdiagnosis is due in part to the overlap between the symptoms of bipolar disorder and the symptoms of other psychiatric disorders, especially unipolar major depression [30,34]. Distinguishing bipolar disorder from other relevant disorders is discussed elsewhere in this topic (see 'Differential diagnosis' below). It has been suggested that the definition of bipolarity be extended to include "bipolar spectrum disorder [7,35]," which has been defined variously as major depression plus subthreshold bipolar symptoms that do not meet criteria for mania or hypomania [36,37], as well as recurrent major depressive episodes with an early age of onset (eg, <25 years) plus a family history of bipolar disorder [38]. However, the concept of bipolar spectrum disorder is disputed [31,39,40]. Bipolar I disorder Bipolar I disorder is diagnosed in patients with one or more manic (table 2) or mixed (concurrent mania and major depression (table 1)) episodes [6]. Hypomania (table 3) often occurs as well (table 5). DSM-IV-TR stipulates that the mood episodes in bipolar I disorder are not better accounted for by schizoaffective disorder and are not superimposed upon schizophrenia (table 6), schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified [6]. Although the course of illness in bipolar I patients nearly always includes at least one episode of major depression, this is not always the case [41-43]. In a prospective study of 163 bipolar I patients who were followed for 15 to 20 years, manic episodes in the absence of major depression (unipolar mania) was observed in 4 percent [42]. Bipolar II disorder Bipolar II disorder is diagnosed in patients with a history of at least one major depressive episode and at least one hypomanic episode, and no history of manic or mixed episodes (table 5) [6]. DSM-IV-TR stipulates that the mood episodes in bipolar II disorder are not better accounted for by schizoaffective disorder and are not superimposed upon schizophrenia (table 6), schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified [6]. Cyclothymic disorder Cyclothymic disorder is diagnosed in patients with numerous periods of both [6]: Hypomanic symptoms or episodes Depressive symptoms that fall short of meeting criteria for a major depressive episode These symptoms recur over a time interval of two or more consecutive years, during which patients are not symptom-free for more than two months at a time [6]. In addition, the symptoms cause significant distress or

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psychosocial impairment, and are not the direct result of a substance or general medical condition. By definition, there are no major depressive, manic, or mixed episodes during the first two years of cyclothymia [6]. After the initial two years, manic or mixed episodes may occur, in which case patients are diagnosed with both bipolar I disorder and cyclothymic disorder. If major depressive episodes occur after the first two years of cyclothymia, both bipolar II disorder and cyclothymic disorder are diagnosed. Bipolar disorder not otherwise specified (NOS) Bipolar disorder not otherwise specified (NOS) is diagnosed in patients with bipolar features that do not meet criteria for a bipolar I, bipolar II, and cyclothymic disorder [6]. Examples of syndromes that are classified as bipolar disorder NOS include: Patients who alternate for several days between manic/hypomanic and depressive symptoms that meet symptom threshold criteria for manic, hypomanic, or major depressive episodes, but not minimal duration criteria Recurrent hypomanic episodes without intercurrent major depressive episodes or symptoms Manic or mixed episodes that are superimposed upon delusional disorder, residual schizophrenia, or psychotic disorder not otherwise specified Course of illness specifiers DSM-IV-TR utilizes several terms to specify the course of illness in bipolar disorder, including [6]: Rapid cycling Rapid cycling is defined as four or more mood episodes during a 12-month period (see "Rapid cycling bipolar disorder: Epidemiology, pathogenesis, clinical features, and diagnosis") Seasonal pattern Seasonal pattern refers to a regular temporal relationship between the onset and remission of major depressive episodes and a particular time of the year (eg, major depression regularly begins in winter and remits in spring) (see "Seasonal affective disorder") Diagnostic hierarchy and change The bipolar disorders form a hierarchy, and the specific disorder that is diagnosed may change over time, depending upon the course of illness [6]: Bipolar disorder NOS can change to cyclothymic disorder if the symptoms persist for two consecutive years and other criteria for cyclothymia are met. Once cyclothymic disorder is diagnosed, the diagnosis never reverts back to bipolar disorder NOS. Patients with bipolar disorder NOS who suffer episodes of hypomania and major depression are reclassified as bipolar II disorder. Once bipolar II disorder is diagnosed, the diagnosis never reverts back to bipolar disorder NOS. Patients with bipolar disorder NOS or bipolar II disorder who experience manic or mixed episodes are reclassified as bipolar I disorder; patients diagnosed with bipolar I disorder retain this diagnosis indefinitely. There are no established predictors of diagnostic change. As an example, it is not clear which bipolar II patients will incur mania and change diagnosis to bipolar I disorder. In addition, patients who are initially and correctly diagnosed with bipolar disorder may eventually change diagnosis to a different disorder [44]. In an observational study of 95 bipolar patients with psychotic features who were prospectively followed for up to 10 years, the diagnosis changed in 22 percent (primarily to schizophrenia) [45]. DIFFERENTIAL DIAGNOSIS Symptoms of bipolar disorder in adults can overlap with symptoms of other psychiatric disorders, which need to be considered to prevent inappropriate treatment. Some of these other disorders may be comorbid with bipolar disorder (eg substance use disorders, attention deficit hyperactivity disorder, and borderline personality disorder) [46,47]. The differential diagnosis of bipolar disorder in children, adolescents, and geriatric patients is discussed separately. (See "Bipolar disorder in children and adolescents: Assessment and diagnosis", section on 'Differential diagnosis' and "Geriatric bipolar disorder: Epidemiology, clinical features, assessment, and diagnosis", section on 'Differential diagnosis'.).

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Unipolar major depression Episodes of major depression occur in both unipolar major depression (major depressive disorder) and bipolar disorder; however, patients with bipolar disorder have a lifetime history of manic/hypomanic and/or mixed episodes, whereas patients with unipolar major depression do not [6]. Nevertheless, bipolar disorder is often misidentified as unipolar major depression [48-53] because the mood episode at onset of bipolar disorder is often a depressive episode [54-56], multiple episodes of major depression may occur prior to the first lifetime episode of mania or hypomania [57], and depressive symptoms occur more frequently than mood elevated symptoms [58,59]. In addition, clinicians may not recognize mania/hypomania due to the presence of comorbid disorders [60,61], and patients often underreport mania/hypomania (eg, episodes that occurred years earlier may be forgotten) [2]. The diagnostic criteria for bipolar major depression and unipolar major depression are identical and there are no pathognomonic signs that distinguish the two [6,62]. However, replicated findings suggest that the following symptoms may be more common in bipolar depression than unipolar depression [62-67]: Psychotic features (eg, delusions and hallucinations) Atypical depressive features such as hypersomnia, hyperphagia, and leaden paralysis (limbs feel heavy as though made of lead and are difficult to move) Subthreshold manic/hypomanic symptoms (ie, mood elevated symptoms not meeting syndromal criteria for mania or hypomania) In addition, multiple studies have found that the following clinical features may be more common in patients with unipolar major depression who eventually experience mania/hypomania and change diagnosis to bipolar disorder, compared with unipolar depressed patients who do not change diagnosis [36,62,68,69]: Younger age of onset of first lifetime episode of major depression (eg, age <25 years) Family history of bipolar disorder Multiple (eg, at least three to five) recurrences of major depression Poor response to antidepressants (eg, failure to respond to at least two treatment trials) An epidemiologic study that compared bipolar disorder (N = 1429 individuals) with unipolar major depression (N = 5695 individuals) found that [65]: The first lifetime depressive episode occurred six years earlier in bipolar disorder than in unipolar depression (age 24 versus 30 years). Prevalence of comorbid anxiety, substance use, and personality disorders was greater in bipolar disorder than in unipolar depression. Social functioning was poorer in bipolar disorder than in unipolar depression. The diagnosis of unipolar major depression is discussed separately. (See "Clinical manifestations and diagnosis of depression", section on 'Major depression'.) Schizoaffective disorder Schizoaffective disorder and bipolar I disorder are both characterized by manic, major depressive, and mixed episodes, as well as psychotic symptoms (eg, delusions and hallucinations), agitation, irritability, and catatonia [6]. However, the two disorders differ in the timing of psychotic symptoms. In bipolar I disorder, psychosis occurs only in the context of mood episodes; by contrast, psychosis in schizoaffective disorder can and does occur in the absence of mood episodes. Schizophrenia Schizophrenia (table 6) and bipolar disorder may both manifest psychosis as well as episodes of major depression [6]. The primary distinguishing feature is that in schizophrenia, psychotic symptoms occur in the absence of prominent mood symptoms; in bipolar disorder, psychosis occurs only during manic, major depressive, or mixed episodes. The diagnosis of schizophrenia is discussed separately. (See "Schizophrenia: Clinical manifestations, course, assessment, and diagnosis", section on 'Diagnosis'.) Substance induced mood disorder Mood disturbances that are limited to intoxication or withdrawal from a drug of abuse, or to treatment with an antidepressant, and are judged to be etiologically related to the mood disturbance, are classified as a substance induced mood disorder rather than a mood disorder such as bipolar disorder [6]. These mood disturbances can manifest as an elevated, expansive, irritable or depressed mood, or as

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anhedonia. Evidence that mood disturbances may be better accounted for by a mood disorder, such as bipolar disorder, includes the following clinical features: The mood disturbance precedes onset of the substance use The symptoms persist for a substantial period of time (eg, one month) after intoxication or withdrawal from the substance History of recurrent mood episodes Family history of mood disorders Attention deficit hyperactivity disorder Symptoms that are common to both attention deficit hyperactivity disorder (ADHD) and mania/hypomania include impaired attention and concentration; distractibility and frequent changes in activity or plans; difficulty with task completion; increased activity, restlessness, and talking; and disinhibited and inappropriate behavior [70-72]. However, mania is accompanied by inflated self esteem and grandiosity, flight of ideas (abrupt changes from one topic to another that are based upon understandable associations), decreased need for sleep, and excessive involvement in pleasurable activities; these symptoms do not occur in ADHD [6]. In addition, major depression nearly always occurs in bipolar disorder, but is absent in ADHD. The diagnosis of ADHD is discussed separately. (See "Adult attention deficit hyperactivity disorder", section on 'Differential diagnosis'.) Borderline personality disorder The alternating mood syndromes ("mood swings") and irritability of bipolar disorder can resemble the affective instability and uncontrolled anger of borderline personality disorder [73,74]. Recurrent suicidal ideation and behavior, problematic impulsive behaviors (eg, excessive spending sprees, sexual promiscuity, substance abuse, and reckless driving), and poor psychosocial functioning are also common to bipolar disorder and borderline personality disorder [6]. One distinguishing feature is that the depressive or mood elevated syndromes in bipolar disorder are longer in duration (eg, lasting days to weeks) compared with the labile affective states of borderline personality disorder (eg, lasting minutes to hours). In addition, bipolar mood syndromes are less connected to events in the environment; by contrast, the mood lability of borderline personality disorder is often triggered by stressors such as perceived rejection or failure. Borderline personality disorder is also marked by unstable and intense interpersonal relationships, identity disturbance (fluctuating self-image or sense of self), chronic feelings of emptiness, and frantic efforts to avoid abandonment; these features are not characteristic of bipolar disorder. The diagnosis of borderline personality disorder is discussed separately. (See "Borderline personality disorder: Epidemiology, clinical features, diagnosis, and differential diagnosis", section on 'Diagnosis'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient information: Bipolar disorder (The Basics)") Beyond the Basics topics (see "Patient information: Bipolar disorder (manic depression) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Difficulties in diagnosing bipolar disorder often leave patients waiting for years to receive the correct diagnosis after onset of symptoms. (See 'Introduction' above.) The initial clinical evaluation of patients with a possible diagnosis of bipolar disorder includes a psychiatric and general medical history, mental status and physical examination, and focused laboratory tests. The

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psychiatric history and mental status examination should include questions about major depression (table 1), mania (table 2), hypomania (table 3), mixed episodes (major depression concurrent with mania), suicidal ideation and behavior, psychotic features (delusions or hallucinations), and comorbid psychiatric and general medical disorders. (See 'Assessment' above.) Although screening for bipolar disorder is often recommended, it is not known whether screening improves patient outcomes. It is also not clear that bipolar screening instruments perform well enough to warrant routine use. (See 'Screening instruments' above.) The American Psychiatric Association's Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) is used to diagnose bipolar mood episodes, which include (see 'Mood episodes' above): Mania (table 2) Hypomania (table 3) Major depression (table 1) Mixed episodes Bipolar I disorder is diagnosed in patients with one or more manic or mixed episodes. Nearly all patients suffer at least one episode of major depression, and hypomania often occurs as well. (See 'Bipolar I disorder' above.) Bipolar II disorder is diagnosed in patients with a history of at least one major depressive episode and at least one hypomanic episode, and no history of manic or mixed episodes. (See 'Bipolar II disorder' above.) Cyclothymic disorder is diagnosed in patients with numerous periods of both hypomanic symptoms/episodes, and depressive symptoms that fall short of meeting criteria for a major depressive episode. Symptoms recur over a time interval of two or more consecutive years, during which the patient is not symptom-free for more than two months at a time. (See 'Cyclothymic disorder' above.) Bipolar disorder not otherwise specified (NOS) is diagnosed in patients with bipolar features that do not meet criteria for a bipolar I, bipolar II, and cyclothymic disorder. As an example, bipolar disorder NOS includes patients who alternate for several days between manic/hypomanic and depressive symptoms that meet symptom threshold criteria for manic, hypomanic, or major depressive episodes, but not minimal duration criteria. (See 'Bipolar disorder not otherwise specified (NOS)' above.) The differential diagnosis of bipolar disorder includes unipolar major depression, schizoaffective disorder, schizophrenia, substance induced mood disorder, attention deficit hyperactivity disorder, and borderline personality disorder. (See 'Differential diagnosis' above.) Use of UpToDate is subject to the Subscription and License Agreement. Topic 86602 Version 4.0

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GRAPHICS DSM-IV-TR diagnostic criteria for major depression

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 depressed mood or loss of interest or pleasure.
(Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.) Depressed mood most of the day, nearly every day (or alternatively can be irritable mood in children and adolescents) Markedly diminished interest or pleasure in all, or almost all, activities, nearly every day Significant weight loss while not dieting, weight gain, or decrease or increase in appetite Insomnia or hypersomnia nearly every day Psychomotor agitation or retardation nearly every day Fatigue or loss of energy nearly every day Feelings of worthlessness or excessive or inappropriate guilt nearly every day Diminished ability to think or concentrate, or indecisiveness, nearly every day 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 do not meet criteria for a Mixed Episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of substance or a general medical condition. E. The symptoms are not better accounted for by Bereavement, ie, after the loss of a loved one, the symptoms persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. American Psychiatric Association, Washington, DC 2000.

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DSM-IV-TR diagnostic criteria for mania

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary). B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1) Inflated self-esteem or grandiosity 2) Decreased need for sleep (eg, 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 (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7) Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The symptoms do not meet criteria for a mixed episode. D. The mood disturbance 1) is sufficiently severe to cause marked impairment in occupational functioning, usual social activities, or relationships with others, 2) necessitates hospitalization to prevent harm to self or others, or 3) has psychotic features. E. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000). American Psychiatric Association.

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DSM-IV-TR diagnostic criteria for hypomania

A. A distinct period of persistently elevated, expansive, or irritable mood, lasting at least 4 days, that is clearly different from the usual nondepressed mood. B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1) Inflated self-esteem or grandiosity 2) Decreased need for sleep (eg, 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 (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7) Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, 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 person when not symptomatic. D. The disturbance in mood and the change in functioning are observable by others. E. The episode 1) is not severe enough to cause marked impairment in social or occupational functioning, 2) does not necessitate hospitalization, and 3) does not have psychotic features. F. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism). Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, ECT, light therapy) should not count toward a diagnosis of bipolar II disorder.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000). American Psychiatric Association.

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Mood disorder questionnaire

1. Has there ever been a period of time when you were not your usual self and... ...you felt so good or so hyper that other people thought you were not your normal self or you were so hyper that you got into trouble? ...you were so irritable that you shouted at people or started fights or arguments? ...you felt much more self-confident than usual? ...you got much less sleep than usual and found you didn't really miss it? ...you were much more talkative or spoke faster than usual? ...thoughts raced through your head or you couldn't slow your mind down? ...you were so easily distracted by things around you that you had trouble concentrating or staying on track? ...you had much more energy than usual? ...you were much more active or did many more things than usual? ...you were much more social or outgoing than usual, for example, you telephoned friends in the middle of the night? ...you were much more interested in sex than usual? ...you did things that were unusual for you or that other people might have thought were excessive, foolish, or risky? ...spending money got you or your family into trouble? 2. If you checked YES to more than one of the above, have several of these ever happened during the same period of time? Please circle one response only. 3. How much of a problem did any of these cause you - like being unable to work; having family, money, or legal troubles; getting into arguments or fights? Please circle one response only. No problem Minor problem Moderate problem Serious problem Yes No Yes No

Patients screen positively for bipolar disorder if they answer "yes" to seven or more items in section 1, "yes" in section 2, and "moderate problem" or "serious problem" in section 3. The mood disorder questionnaire should not be used to diagnose bipolar disorder. Patients who screen positive should be interviewed to establish the diagnosis; including family members is often helpful.
Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry 2000; 157:1873. Reprinted with permission from the American Journal of Psychiatry (Copyright 2000). American Psychiatric Association.

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Comparison of DSM-5 criteria for bipolar I disorder and bipolar II disorder

Bipolar I disorder
Manic episode(s) Hypomanic episode(s) Major depressive episode(s) Mixed features Anxious distress Rapid cycling Psychotic features Catatonia Yes Commonly occur, but not required Usually occur, but not required May occur May occur May occur May occur May occur Yes May occur May occur May occur May occur May occur

Bipolar II disorder
No Yes

Data from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifrth Edition, American Psychiatric Association, Arlington, VA, 2013.

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DSM-5 diagnostic criteria for schizophrenia

A. Two (or more) of the following, each present for a significant portion of time during a one-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 (eg, frequent derailment or incoherence) 4. Grossly disorganized or catatonic behavior 5. Negative symptoms (ie, 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 six-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (ie, 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 (eg, 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 active0phase 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 direct physiological effects of a substance (eg, 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 one 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 (ie, 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

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Specify if:
With 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 seven days) on a 5-point scale ranging from 0 (not present) to 4 (present and severe). Note: Diagnosis of schizophrenia can be made without using this severity specifier.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All Rights Reserved.

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