Bipolar Disorder

Background

• Bipolar disorder is characterized by recurrent episodes of elevated or irritable mood and depression, accompanied by changes in sleep and energy and associated with cognitive, physical, and behavioral symptoms.
• Bipolar I disorder is characterized by at least 1 episode of mania, and usually episodes of depression and/or hypomania.
• Bipolar II disorder is characterized by a history of major depressive episodes and hypomanic episodes only, without episodes of mania.
• There are a number of clinical diagnostic features (specifiers) for bipolar disorder, for example:
  • rapid cycling, transitory state characterized by at least 4 episodes of mania, hypomania, and/or depression over the past year
  • mixed features, which includes combined features of mood episodes of opposite polarity
  • mania with psychotic features
• Bipolar I and II are reported to affect 2% of the world population; the initial episode is most common in persons who are < 25 years old.
• Heritability is high and bipolar disorder may share susceptibility genes and inheritance patterns with schizophrenia and major depressive disorder. Environment plays a role as well, as life events and chronic stressors may precipitate and perpetuate mood episodes.
• Comorbid psychiatric disorders are common, especially anxiety disorders, impulse control disorders, attention deficit hyperactivity disorders, borderline personality disorder, and substance use disorders.
• The prognosis is associated with an increased risk of premature all-cause and cause-specific death; 25%-50% of patients with bipolar disorder attempt suicide at least once, and approximately 4%-15% of bipolar patients die as a result of a suicide attempt.

Evaluation

• The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) provides diagnostic criteria for bipolar disorder.
  • Mania is defined as at least 1 week (or any duration if hospitalization is necessary) of abnormally and persistently elevated, expansive, or irritable mood, and abnormally and persistently increased goal-directed activity or energy along with at least 3-4 other manic symptoms, such as, grandiosity, decreased need for sleep, or pressured speech, which result in marked impairment in functioning, hospitalization, or psychosis.
  • Hypomania has the same elements as mania except that the symptoms need only be present for 4 days and while they represent a noticeable change from usual behavior, they do not cause marked impairment in functioning, hospitalization, or psychosis.
  • A major depressive episode is defined as having at least 5 depressive symptoms within the same 2-week period which cause clinically significant distress or impairment in functioning, such as:
    • depressed mood
    • pervasive loss of interest or pleasure in activities (either this symptom or depressed mood must be present)
    • decreased ability to think or concentrate, or indecisiveness
    • fatigue or loss of energy
    • feelings of worthlessness or excessive or inappropriate guilt
    • insomnia or hypersomnia
    • psychomotor agitation or retardation observable by others
    • recurrent thoughts of death, recurrent suicidal ideation, suicide attempt, or specific plan for committing suicide
    • significant weight change (5% in 1 month, not dieting) or change in appetite
    • see also Major Depressive Disorder (MDD) for additional information
  • Cyclothymic Disorder is characterized by episodes of hypomanic and depressive experiences occurring over at least 2 years that do not meet the full DSM-5 diagnostic criteria for hypomania or major depressive disorder.
• Consider bipolar disorder in all patients presenting with depression, particularly if the symptoms first occurred before age 25 years, and in all patients with symptoms of mania. It is not possible to distinguish unipolar from bipolar depression in the absence of a history of a prior manic or hypomanic episode, but some characteristics that may suggest bipolar depression include:
  • atypical depressive features, such as, hypersomnia, increased appetite, feelings of heaviness, and difficulty moving limbs or body
  • family history of bipolar disorder
  • labile moods
  • multiple episodes of depression
  • onset of depression at ≤ 13 years old
  • psychotic features or feelings of pathological guilt
  • psychomotor retardation
• Consider basing the diagnosis of bipolar disorder upon a careful history and physical, a mental state exam, and the exclusion of other causes for manic or depressive symptoms, such as, substance abuse, thyroid disorder, neurological disease, dementia, and metabolic disturbance.
  • Suspect secondary mania especially in patients presenting with first episode in prepuberty or after age ≥ 40 years.
  • Consider testing with a baseline complete blood count, a basic metabolic panel, liver function tests, thyroid function studies, and a urine toxicology screen.
  • For patients with new-onset psychosis, consider adding a brain magnetic resonance imaging (MRI), an electroencephalogram (EEG), and specific testing for heavy metals, urine porphyrins, hepatitis C, and syphilis.

Management

• Consider mood stabilizers, such as, lithium or valproate, and second-generation antipsychotics for the primary treatment of bipolar disorder.
  • For acute mania with mixed features, consider a second-generation antipsychotic, such as, quetiapine; add valproate or lithium if the response is unsatisfactory.
  • For acute nonmixed mania, consider lithium, quetiapine, and/or valproate or other second-generation antipsychotics. If there is an unsatisfactory response, consider a switch to another second-generation antipsychotic, or a switch to valproate if the patient was started on lithium and is not pregnant or likely to become pregnant. For patients with rapid cycling, consider aripiprazole or quetiapine as first-line options in patients without current psychoses.
  • For acute bipolar depression, options include second-generation antipsychotics (such as quetiapine, lurasidone, cariprazine, or olanzapine plus fluoxetine), lithium, or lamotrigine. Second-generation antipsychotics should be considered over lithium or lamotrigine if patient has psychotic symptoms or mixed features.
  • For patients with rapid cycling bipolar depression, consider quetiapine or lurasidone as the first-line options with or without cognitive behavioral therapy.
• For maintenance monotherapy in patients with bipolar disorder, consider lithium or valproate. If the patient is unable or unwilling to take lithium or valproate, consider lamotrigine or a second-generation antipsychotic.
• For patients currently on maintenance treatment who experience acute symptoms:
  • Assess the medication adherence and optimize the medication dose if possible before adding or changing therapy.
  • For patients with a history of mania or with mixed features, consider stopping the antidepressant.
  • In patients with psychotic features, add a second-generation antipsychotic to the regimen.
  • Consider adding a second agent from another class; for example, if on an antipsychotic, add a mood stabilizer, or if on a mood stabilizer, consider the addition of a second-generation antipsychotic.
• Consider electroconvulsive therapy (ECT):
  • for severe manic episodes
    • to achieve a rapid and short-term improvement in patients resistant to medication
    • with a history of a good response to ECT
    • if the medication adverse effects are intolerable
  • for severe depressive episodes if there are urgent indications, such as
    • severe suicidality
    • catatonia
    • insufficient oral intake
    • limited ability to use psychotropics, such as, pregnancy
    • if rapid response essential
• When discontinuing an antipsychotic, antidepressant, or mood stabilizer, slowly reduce the dose over time.
• For older patients (≥ 60 years old), consider the higher incidence of potential comorbidities and drug interactions in this patient population. Consider starting with lower doses of medications and avoid antipsychotics, if possible, to reduce adverse effects.
• In pregnant women or women of childbearing age, several agents may have adverse or teratogenic effects on a fetus. Low-dose first- or second-generation antipsychotics may be preferred over the following:
  • carbamazepine
  • lithium (may be continued during pregnancy with close monitoring of levels)
  • paroxetine
  • valproate
  • long-term treatment with benzodiazepines
• Consider adjunctive psychosocial and psychotherapeutic interventions for 6-9 months following an acute manic or depressive episode to help prevent a relapse.
  • Patients with mania and mixed features may benefit from psychosocial treatments that emphasize consistency with medicine but may not respond well to intensive psychotherapy due to a lack of insight into the disease and a rejection of intervention.
  • Patients with depression may benefit from cognitive behavioral therapy, family focused therapy, or interpersonal and social rhythm therapy.
• Provide close monitoring with at least yearly evaluations, and periodic lab work depending on the medication(s).