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Am Fam Physician. 2021;103(4):227-239

Patient information: A handout on this topic is available at https://familydoctor.org/condition/bipolar-disorder.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Bipolar disorders are common, recurrent mental health conditions of variable severity that are difficult to diagnose. Affected individuals have higher rates of other mental health disorders, substance use disorders, and comorbid chronic medical illnesses. New diagnostic criteria and specifiers with attention on mixed features and anxious distress aid the physician in recognizing episode severity and prognosis. Physicians should consider bipolar disorder in any patient presenting with depression. Pharmacotherapy with mood stabilizers, such as lithium, anticonvulsants, and antipsychotics, is a first-line treatment that should be continued indefinitely because of the risk of patient relapse. Active lifestyle approaches include good nutrition, exercise, sleep hygiene, and proper weight management. Monotherapy with antidepressants is contraindicated during episodes with mixed features, manic episodes, and in bipolar I disorder. Ongoing management involves monitoring for suicidal ideation, substance use disorders, treatment adherence, and recognizing medical complications of pharmacotherapy. Psychotherapy is a useful adjunct to pharmacotherapy. Patients and their support systems should be educated about the chronic nature of this illness, possible relapse, suicidality, environmental triggers (e.g., seasonal light changes, shift work, other circadian disruption), and the effectiveness of early intervention to reduce complications.

Bipolar disorders comprise recurrent episodes of elevated mood and depression.1 The relapse rate is more than 70% over five years.2 Definitions of the various types of bipolar disorders are provided in Table 13,4; diagnostic criteria are listed in Table 2.3 Hypomania can occur in bipolar I and II disorders, whereas mania, which may include psychosis, appears only in bipolar I disorder. The nature and prognosis of the current episode and the likelihood of future ones can be described with specific attributes3 (Table 335 ).

DisorderDefinitions
Bipolar I disorderManic or mixed feature episode with or without psychosis and/or major depression
Bipolar II disorderHypomanic episode with major depression; no history of mania, but can have a history of hypomania
CyclothymiaHypomanic and depressive symptoms that do not meet bipolar II disorder criteria, no major depressive episodes, occurring over two years, with no more than two months free of symptoms
Bipolar disorder, not otherwise specifiedDoes not meet criteria for major depression, bipolar I disorder, bipolar II disorder, or cyclothymia (e.g., less than one week of manic symptoms, without psychosis or hospitalization)
Bipolar disorder, mixed features type or major depressive disorder, mixed features typeMixed type, also known as mixed features, is a recent specifier that includes concurrent features of hypomania or mania and depression; patients who do not meet full criteria for bipolar disorders remain categorized as having unipolar depression
Substance-induced mania (include name of substance)Examples include steroids, alcohol, cocaine, or prescription antidepressants
UnspecifiedUsed for suspicion (e.g., in emergency department)
Diagnostic criteria
For a diagnosis of bipolar I disorder, it is necessary to meet the 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
  1. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least one week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

  2. 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:

    Inflated self-esteem or grandiosity.

    Decreased need for sleep (e.g., feels rested after only three hours of sleep).

    More talkative than usual or pressure to keep talking.

    Flight of ideas or subjective experience that thoughts are racing.

    Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

    Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., purposeless non–goal-directed activity).

    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).

  3. 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.

  4. The episode is not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication, other treatment) or 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 physiologic 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.
Hypomanic episode
  1. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least four consecutive days and present most of the day, nearly every day.

  2. 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:

    Inflated self-esteem or grandiosity.

    Decreased need for sleep (e.g., feels rested after only three hours of sleep).

    More talkative than usual or pressure to keep talking.

    Flight of ideas or subjective experience that thoughts are racing.

    Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

    Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.

    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).

  3. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

  4. The disturbance in mood and the change in functioning are observable by others.

  5. 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.

  6. The episode is not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition.


Note: A full hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiologic effect of that treatment is sufficient evidence for a hypomanic 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 hypomanic episode, nor necessarily indicative of a bipolar diathesis.
Note: Criteria A–F constitute a hypomanic episode. Hypomanic episodes are common in bipolar I disorder but are not required for the diagnosis of bipolar I disorder.
Major depressive episode
  1. A. Five (or more) of the following symptoms have been present during the same two-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.

    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.)

    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).

    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.)

    Insomnia or hypersomnia nearly every day.

    Psychomotor agitation or retardation nearly every day (observable by others; not merely subjective feelings of restlessness or being slowed down).

    Fatigue or loss of energy nearly every day.

    Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

    Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

    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.

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

  3. The episode is not attributable to the physiologic 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.
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.
Specify:
With anxious distressWith melancholic featuresWith mood-incongruent psychotic featuresWith seasonal pattern
With mixed featuresWith atypical featuresWith catatonia
With rapid cyclingWith mood-congruent psychotic featuresWith peripartum onset
DSM-5 specifiersBipolar I disorderBipolar II disorderMajor depressive disorder
Anxious distress
 Associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse. It requires two or more of the following:
Feeling keyed up or on edge, feeling restless, difficulty concentrating because of worry, fear that something awful might happen, feeling of losing control
YesYesYes
Atypical features
 Sleeps more, eats more, feels “heavy” or “leaden”
Possible, when depressedPossible, when depressedPossible, depending on type of depression
CatatonicYesYes, when depressed only; otherwise, bipolar I disorderYes
Current episode severity
 Mild: symptoms sufficient to meet only criteria for diagnosis with mild functional impairment
 Moderate: between mild and severe
 Severe: symptoms causing severe distress and functional impairment
YesYesYes
MelancholiaYes, if depressedYes, if depressedYes
Mixed features state
 Symptoms of depressed mood and mania or hypomania within the same episode
Yes, can be triggered or worsened by the use of antidepressantsYesYes, recovery from depression can manifest first with return of energy before mood improvement, which can look similar and is a vulnerable time for patients
Peripartum onsetYesYesYes
Psychotic features
 Mood congruent or incongruent, which is defined as mood state consistent with depressed mood or manic state or inconsistent with state
YesYes, when depressed only; otherwise, bipolar I disorderYes
Rapid cycling
 Can be applied to bipolar I disorder if the patient has had at least four mood episodes in the previous 12 months and if the episodes were demarcated by partial or full remission for at least two months or a switch to an episode of opposite polarity (e.g., major depressive episode to manic episode)*
YesNoNo
Seasonal component
 Specifier for course of illness
Yes, often hypomania or mania triggered in the spring or with change in light or shift workYes, often hypomania triggered in the spring or with change in light or shift workYes, if it has a component of seasonal affective disorder

Epidemiology

Bipolar disorders, affecting more than 1% of the world's population, have no predilection for race, sex, ethnicity, or socioeconomic status.4 Bipolar I disorder has a higher lifetime incidence than bipolar II disorder (0.6% and 0.4%, respectively).6 The mean age at onset is 18 years in bipolar I disorder and 22 years in bipolar II disorder.7

One-fourth of patients presenting with depression or anxiety in a primary care setting have been diagnosed with a bipolar disorder.8 Three-fourths of patients with bipolar disorder have a history of three additional and concurrent mental health conditions, most commonly anxiety disorders, impulse control and attention-deficit/hyperactivity disorders, and substance use disorders, which are associated with worse outcomes.9,10 One-third of patients who have been diagnosed with bipolar disorder will attempt suicide in their lifetime, 16% will have attempted suicide within the past year, and 6% to 7% complete suicide.11,12 Twenty-six percent of suicides occur within six weeks of a hospital discharge.11,12 Patients who have anxious distress have a higher risk of suicide, longer illness duration, and poorer response to medication.13

Etiology

Bipolar disorders are multifactorial conditions with a genetic predisposition affected by stress and the environment. Children of parents with bipolar disorders have a 4% to 15% risk of being affected, compared with a less than 2% risk in children of parents without bipolar disorder.12 Acute stressors are often associated with the initial onset of illness and sometimes with recurrence.5 These include stressful life events, adverse childhood events and trauma, suicide of a family member, and disruptions in the sleep cycle.14 Biologic susceptibility, central and peripheral nervous system inflammation, abnormal endocrine and neuronal pathways, and mitochondrial dysfunction inheritance patterns have been implicated in bipolar disorders.15,16

Clinical Presentation

Patients typically present for treatment with depression or anxiety or with mixed features, which include concurrent mania and depression.2,8 This depression may be indistinguishable from unipolar depression12 (Table 412,17,18 ) and often starts in early childhood.19 Women are more susceptible during hormonal fluctuations, such as during menses, childbirth, and menopause.20 Diagnosis may be delayed because a series of depressive episodes may occur before a mixed features, manic, or hypomanic episode manifests. Patients typically do not present for care with hypomania because, despite possible negative consequences, it is often seen as a desirable state by the patient.21 Physicians should specifically ask patients who are depressed about symptoms of mania or hypomania (Table 4).12,17,18 Shift work, travel across time zones, and seasonal light changes such as during daylight savings time can trigger hypomania and mania. As many as 25% of patients may present with a seasonal pattern.22,23

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