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Bipolar disorder

Last updated: September 23, 2021

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Bipolar disorder is a psychiatric condition characterized by episodes of mania (or hypomania) and major depression, interspersed with periods of normal mood and functioning. Men and women are equally affected, and there is a strong genetic component to the disease. During manic episodes, patients may experience elevated mood, talkativeness, racing thoughts, and psychosis, and can endanger themselves or others. Depressive episodes are characterized by sadness, anhedonia, and hopelessness. Although episodes of mania or depression can occur at any time, they are especially triggered by environmental factors, such as lack of sleep or psychosocial stress. Manic episodes are treated acutely with lithium, antipsychotics, and benzodiazepines. Lithium is also commonly used for long-term treatment, as is valproic acid.

  • Sex: = [1]
  • Age of onset [2]
    • The average age of onset is 20 years
    • The frequency of depressive and manic episodes increases with age.
  • Lifetime prevalence
    • General population: 1–3%
    • First-degree relative with bipolar disorder: up to 10%
    • Monozygotic twin: 40–70%

Patients with bipolar disorder have a very high risk of suicide!

Epidemiological data refers to the US, unless otherwise specified.

  • Multifactorial origin
    • Strong genetic componentincreased risk if first-degree relative is affected (see “Epidemiology” above)
    • ↑ Paternal age → ↑ mutations during spermatogenesis ↑ risk of bipolar disorder in offspring
  • Triggers [2]
    • Medications (e.g., dexamethasone)
    • Childhood traumatic experiences
    • Psychosocial stress
    • Sleep disturbances
    • Physical illness

Bipolar disorder is characterized by recurring periods featuring symptoms of mania/hypomania and/or depression, interspersed with asymptomatic periods. See “DSM-5 criteria for bipolar disorder” for details. [3]

To remember the features of a manic episode, think: “DIG FAST” (Distractibility, Irresponsibility, Grandiosity, Flight of ideas, Activity increase, Sleep deficit, Talkativeness).

To remember the features of major depressive episode, think: “SIG E CAPS” (Sleep (insomnia or hypersomnia), Interest loss (anhedonia), Guilt (low self-esteem), Energy (low energy or fatigue), Concentration (poor concentration or difficulty making decisions), Appetite (decreased appetite or overeating), Psychomotor agitation or retardation, and Suicidality).

Types of bipolar disorder [4][5]

  • Bipolar I disorder: at least one episode of mania. Major depressive or hypomanic episodes usually occur but are not required for diagnosis.
  • Bipolar II disorder: at least one episode of hypomania and one major depressive episode; no previous episodes of mania (distinguishing feature from bipolar I)

In contrast to bipolar II disorder, a history of major depressive episodes is not required for the diagnosis of bipolar I disorder.

Rapid cycling [4][5]

Cyclothymia [4][5]

  • Persistent instability of mood involving numerous periods of depression and periods of hypomania
  • Symptoms are not sufficiently severe or persistent enough to diagnose bipolar disorder.
  • Symptoms last at least 2 years, are present at least half of the time, and are never absent for more than 2 months at a time.

Substance/medication-induced bipolar and related disorder [4][5]

Always do a urine drug screening in patients presenting with mania.

Approach [6][7]

The diagnosis is clinical and based on the DSM-5 criteria for bipolar disorder. Patients presenting with features of an acute episode should prompt a psychiatry consult and, depending on the severity of the episode, an urgent referral for management.

Suspected bipolar disorder [3][6][7]

  • Suspect bipolar disorder in patients presenting with current or previous features of mania/hypomania and/or major depression.
  • Consider using screening tools [3][6]
    • Mood Disorder Questionnaire for manic episodes
    • Patient Health Questionnaire-9 (PHQ-9) for depressive episodes
  • Identify associated features that support the diagnosis, including:
    • Suicide attempt
    • Onset at an early age
    • First-degree relatives with bipolar disorder
  • Obtain a detailed clinical history and physical examination; request laboratory studies based on clinical suspicion.
  • Assess the risk of self-injury and consult psychiatry early for a specialized evaluation.

Patients with known bipolar disorder [6][8]

  • Symptoms suggest an acute episode
    • Assess for suicidal ideation.
    • Identify potential substance misuse as the trigger for the acute episode.
    • Obtain urgent psychiatry consult for management.
  • Follow-up visits or visits not related to bipolar disorder
    • Ask about frequency and severity of acute episodes, symptom control, and medication history
    • Screen for related medical comorbidities (e.g., migraine, metabolic syndrome, type 2 diabetes mellitus). [6][8]

Patients with bipolar disorder have the highest suicide rate among patients with affective disorders. All patients with suspected or confirmed bipolar disorder should be assessed promptly for suicide risk (especially during acute episodes) and evaluated by a psychiatrist. [3]

Patients with bipolar disorder are often misdiagnosed with major depressive disorder because the first presentation is usually a major depressive episode. [6]

Diagnostic studies [6][7]

Studies help rule out differential diagnoses and detect conditions that may affect management. A complete history and physical examination should guide the requested studies.

DSM-5 diagnostic criteria for bipolar disorder [8]

Manic and hypomanic episodes

DSM-5 criteria for manic and hypomanic episodes [8]

Manic episode Hypomanic episode
Definition
  • Abnormally and persistently elevated, expansive, or irritable mood alongside increased goal-directed behavior, activity, or energy that are unattributable to an organic psychic disorder or psychotropic substances
Duration
  • Most of the day for at least ≥ 7 consecutive days
  • Most of the day for ≥ 4 consecutive days
Criteria
  • ≥ 3 of the following:
    • Increased goal-directed activity (sexually, at work, and/or socially ) or psychomotor agitation
    • Increased talkativeness or pressure to keep talking
    • Flight of ideas or racing thoughts
    • Excessive involvement in risky activities that can potentially lead to negative consequences (e.g., compulsive shopping, indiscreet sexual behavior, impulsive financial investments)
    • Decreased need for sleep
    • Heightened self-esteem or grandiosity
    • Distractibility
Extent of dysfunction
  • One of the following:
    • Significant professional/social dysfunction
    • The patient requires hospitalization (risk of harm to self or others).
    • Psychotic features may be present.
  • There is an unequivocal change from baseline that:
    • Is observable by others
    • Does not result in significant professional/social dysfunction or hospitalization
  • Psychotic features are not present.

A key difference between mania and hypomania is the intensity of the symptoms. Symptoms of mania are much more intense than those of hypomania, result in significant dysfunction, and manic patients often require hospitalization.

If psychotic symptoms are present, the episode is by definition manic, not hypomanic.

Major depressive episodes

DSM-5 diagnostic criteria for major depressive episode [8]

Definition

  • A change in usual function that is characterized by depressed mood and/or anhedonia, accompanied by other related symptoms, and not attributable to psychoactive substances, organic disease, or significant loss
Duration
  • Symptoms are present almost every day, for at least 2 weeks.
Criteria
  • ≥ 5 of the following:
    • Depressed mood lasting for most of the day
    • Sleep disturbance (insomnia or hypersomnia)
    • Loss of interest or anhedonia
    • Feelings of worthlessness or guilt
    • Fatigue or loss of energy
    • Diminished concentration or ability to make decisions
    • Significant change in weight (not associated with dieting) or appetite
    • Psychomotor changes (agitation or retardation)
    • Recurrent suicidal ideation or thoughts of death
  • At least one of the symptoms must be depressed mood or anhedonia.
Extent of dysfunction
  • Clinically significant distress or impaired functioning in important areas of life (e.g., work, school)
Bipolar I disorder Bipolar II disorder Cyclothymia Substance/medication-induced bipolar and related disorder [9]
Main features
  • Persistent instability of mood involving numerous periods of depression and periods of hypomania
  • Manic or depressive episodes associated with substances/medications

Duration

  • ≥ 2 years
  • Remissions last ≤ 2 months
  • During or soon after substance intoxication/withdrawal, or after exposure to a medication
(Hypo)mania
Depressive episodes
  • May be present or absent
  • Depressive symptoms
  • May be present or absent
Psychotic symptoms
  • May be present or absent
  • Absent
  • Absent
  • May be present or absent
Function
  • Significant social or occupational dysfunction
  • May cause significant social or occupational dysfunction during depressive episodes
  • Significant social or occupational dysfunction
  • Significant social or occupational dysfunction

The differential diagnoses listed here are not exhaustive.

General principles [6][7][10]

Mood stabilizers are a type of drug used as part of the treatment and prevention of episodes of acute mania, hypomania, and depression.

Acute management for mania, hypomania, and depressive episodes [7][10][11]

Pharmacotherapy for patients with acute bipolar disorder episodes [7]
Acute mania [6] Mild to moderate [8]
Severe [8]
Special cases
Acute depression

Antipsychotics are the preferred initial therapy in agitated patients because of their rapid onset of action.

Patients with suicidal ideation should be admitted immediately for emergency management and monitoring by a specialist.

Acute mania is a psychiatric emergency that requires immediate management.

Lithium has a narrow therapeutic index and doses should be individualized according to serum levels and clinical response; an overdose may result in life-threatening lithium toxicity. Lithium is contraindicated in patients with renal dysfunction. [6]

Long-term maintenance treatment [3][7][10][11]

Maintenance treatment of bipolar disorder combines pharmacotherapy with nonpharmacological interventions. Most patients need lifelong maintenance therapy to prevent relapses.

Avoid prescribing antidepressants to patients with bipolar disorder before initiating therapy with mood stabilizers, as antidepressants can precipitate a manic episode. [10]

Lithium is the only maintenance drug shown to lower the risk of suicide. [14]

  1. Sit D. Women and bipolar disorder across the life span. J Am Med Womens Assoc. 2004; 59 (2): p.91-100.
  2. Stovall J. Bipolar Disorder in Adults: Epidemiology and Pathogenesis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/bipolar-disorder-in-adults-epidemiology-and-pathogenesis.Last updated: September 26, 2017. Accessed: December 15, 2017.
  3. Vieta E, Berk M, Schulze TG, et al. Bipolar disorders. Nature Reviews Disease Primers. 2018; 4 (1). doi: 10.1038/nrdp.2018.8 . | Open in Read by QxMD
  4. Bipolar and Related Disorders. http://dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596.dsm03. . Accessed: May 15, 2017.
  5. Suppes T . Bipolar Disorder in Adults: Assessment and Diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/bipolar-disorder-in-adults-assessment-and-diagnosis.Last updated: November 1, 2016. Accessed: May 15, 2017.
  6. Quello SB et al.. Mood disorders and substance use disorder: a complex comorbidity.. Science & practice perspectives. 2005; 3 (1): p.13-21.
  7. Practice guideline for the treatment of patients with bipolar disorder . http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf%20. Updated: April 1, 2002. Accessed: July 11, 2017.
  8. Marzani G, Price Neff A. Bipolar Disorders: Evaluation and Treatment. Am Fam Physician. 2021; 103 (4): p.227-239.
  9. Carvalho AF, Firth J, Vieta E. Bipolar Disorder. N Engl J Med. 2020; 383 (1): p.58-66. doi: 10.1056/nejmra1906193 . | Open in Read by QxMD
  10. Guideline watch: Practice guideline for the treatment of patients with bipolar disorder.
  11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM–5). undefined. 2013 . doi: 10.1176/appi.books.9780890425596 . | Open in Read by QxMD
  12. Yonkers KA et al.. Management of Bipolar Disorder During Pregnancy and the Postpartum Period. Am J Psychiatry. 2004; 161 (4): p.608-620. doi: 10.1176/appi.ajp.161.4.608 . | Open in Read by QxMD
  13. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. The Lancet. 2014; 384 (9956): p.1789-1799. doi: 10.1016/s0140-6736(14)61278-2 . | Open in Read by QxMD
  14. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020; 4 (12): p.2656-2701. doi: 10.1182/bloodadvances.2020001851 . | Open in Read by QxMD
  15. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018; 20 (2): p.97-170. doi: 10.1111/bdi.12609 . | Open in Read by QxMD