Summary
Bipolar disorder is a psychiatric illness 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 often endanger themselves or others. Depressive episodes are characterized by sadness, anhedonia, and hopelessness. Although episodes of mania or depression can occur anytime, they are especially triggered by environmental factors (eg, lack of sleep, 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.
Epidemiology
- Sex: ♀ = ♂ [1]
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Age of onset [2]
- The average age of onset is 20 years
- The frequency of depressive and manic episodes increases with age.
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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.
Etiology
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Multifactorial origin
- Strong genetic component → increased risk if first-degree relative is affected (see “Epidemiology” above)
- ↑ Paternal age → ↑ mutations during spermatogenesis → ↑ risk of bipolar disorder in offspring
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Triggers [2]
- Childhood traumatic experiences
- Psychosocial stress
- Sleep disturbances
- Physical illness
Clinical features
Features of a manic episode, hypomanic episode, or a major depressive episode interspersed with periods of normal mood and functioning
Features of manic and hypomanic episodes [3][4][5]
| Diagnostic criteria according to DSM-V | ||
|---|---|---|
| Manic episode | Hypomanic episode | |
| Core definition |
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| Duration |
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| Criteria |
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| Extent of dysfunction |
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The main 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 and not hypomanic.
To remember the features of a manic episode, think: “DIG FAST” (Distractibility, Irresponsibility, Grandiosity, Flight of ideas, Activity increase, Sleep deficit, Talkativeness).
Major depressive episode [3][4][5]
| Diagnostic criteria according to DSM-V | |
|---|---|
| A |
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| B |
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| C |
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In some patients, the initial diagnosis may be a recurrent depressive disorder, as depressive symptoms might be the only symptoms for several years.
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).
Subtypes and variants
Types of bipolar disorder [3][6]
- 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 [3][6]
- Patients affected by rapid cycling have 4 or more episodes of depression, mania, or hypomania occurring in a single year.
Cyclothymia [3][6]
- 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 [3][6]
- Elevated, disinhibited, or irritable mood with/without depressed mood or anhedonia that develops during or soon after substance intoxication or withdrawal, or after exposure to a medication.
- Common precipitants
Always do a urine drug screening in patients presenting with mania.
Diagnostics
- Screening: structured questionnaires (e.g., the Mood Disorder Questionnaire for manic episodes and Patient Health Questionnaire-9 (PHQ-9) for depressive episodes)
- Clinical diagnosis: See “Clinical features” above.
All patients must be assessed for suicide risk.
Differential diagnoses
| Bipolar I disorder | Bipolar II disorder | Cyclothymia | Substance/medication-induced bipolar and related disorder [7] | |
|---|---|---|---|---|
| Main features |
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| Duration |
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| (Hypo)mania |
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| Depressive episodes |
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| Psychotic symptoms |
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| Function |
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The differential diagnoses listed here are not exhaustive.
Treatment
Acute treatment for mania and hypomania [8][9][10]
Acute mania is considered a psychiatric emergency and requires immediate management. The goal of acute treatment is resolution of mania and psychosis (if present) as well as preventing any harm to the patient or others. Mood stabilizers are a type of drug used to treat acute mania and/or to prevent relapses of manic or hypomanic episodes.
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General principles
- Reduce external stimuli.
- Assess for possible contributing substances (e.g., cocaine, alcohol, phencyclidine).
- Limit access to cars, bank accounts/credit cards, cell phones, etc., because of the potential for reckless behavior.
- Mild to moderate mania: lithium monotherapy or atypical antipsychotics (olanzapine, quetiapine)
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Severe mania: mood stabilizer (lithium or valproate) PLUS antipsychotic
- If a patient does not respond to medication within 1–3 weeks, continue with the antipsychotic and switch lithium to valproate or vice versa.
- If a patient is still not responsive, switch the antipsychotic to another antipsychotic drug.
- If a patient has refractory mania, discontinue pharmacotherapy and switch to ECT.
- Mania/hypomania in pregnancy: typical antipsychotics (e.g., haloperidol) or ECT (if severe or refractory mania) [11]
- Management of agitation: rapid-acting intramuscular atypical antipsychotics (e.g., olanzapine, aripiprazole) or benzodiazepines (e.g., lorazepam) [12]
Antipsychotics are the preferred initial therapy in agitated patients because of their rapid onset of action.
Suicidal patients require immediate management and monitoring to ensure their safety.
Long-term maintenance treatment [8][9]
The goal of maintenance therapy is to prevent future manic episodes, reduce the risk of suicide, and improve social functioning.
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Duration of therapy
- Maintenance therapy is indicated following even a single manic episode.
- Treat for at least 1 year following an acute manic episode.
- In patients who experience 2 or more episodes, long-term or lifetime therapy should be considered.
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Medication
- First-line: the drug(s) that resolved the acute manic episode
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Second-line
- Lithium (first choice)
- Valproic acid (useful for patients with renal dysfunction)
- Lamotrigine
- Quetiapine
- Third-line
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Refractory or severe bipolar episodes
- Combination therapy with lithium; or valproic acid PLUS atypical antipsychotics (e.g., quetiapine, aripiprazole, olanzapine, risperidone)
- Carbamazepine
- Oxcarbazepine
- Asenapine
- Lurasidone
- Paliperidone
- Severe depression or predominantly depressive bipolar II disorder: Antidepressants may be started after initiating mood stabilizers.
In a patient with bipolar disorder, antidepressants should not be used before initiating therapy with mood stabilizers because antidepressants can precipitate a manic episode!
Lithium should not be administered to patients with renal dysfunction! An overdose may result in life-threatening lithium toxicity.
Lithium is the only maintenance drug shown to lower suicide risk.