At least one lifetime manic episode; depressive and hypomanic episodes common but not required for diagnosis.
Also known as: bipolar disorder, bipolar I, mania, manic-depressive illness
Overview
A chronic mood disorder defined by at least one lifetime manic episode — a distinct period of abnormally elevated, expansive, or irritable mood and increased goal-directed activity lasting >=7 days (or any duration if hospitalization is required) with associated DIG FAST symptoms. Most patients also experience major depressive episodes and hypomania, but neither is required for diagnosis.
Epidemiology
Lifetime prevalence ~1% (bipolar I); ~2.4% for bipolar spectrum. Equal sex distribution. Mean onset late teens to early 20s. High familial loading — heritability ~70-85%.
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Substance use, especially stimulants and cannabis in adolescence
Sleep disruption, jet lag, shift work — common precipitants
Childhood trauma associated with earlier onset and worse course
Pathophysiology
Polygenic risk with dysregulation of monoaminergic and glutamatergic systems, circadian rhythm instability, mitochondrial dysfunction, and altered intracellular signaling (GSK-3, inositol pathways — targets of lithium and valproate). Neuroimaging shows amygdala hyperactivity and reduced prefrontal regulation during mood episodes.
Clinical presentation
Symptoms
Manic episode: elevated, expansive, or irritable mood >=1 week with increased energy/activity
DIG FAST: Distractibility, Indiscretion (risky behaviors), Grandiosity, Flight of ideas, decreased need for Sleep, increased goal-directed Activity, increased Talkativeness/pressured speech
Psychotic features in severe mania — grandiose or persecutory delusions, mood-congruent hallucinations
Depressive episodes often predominate over a patient's lifetime
Mixed features — manic and depressive symptoms co-occurring; high suicide risk
Signs / physical exam
Pressured rapid speech, flight of ideas, tangential thought process
Hyperactivity, irritability, poor insight
Disheveled appearance with flamboyant dress in some cases
Cognitive impairment during acute episodes
Classic findings
Manic patient with reduced need for sleep (e.g., sleeping 2-3 hours and feeling rested), spending sprees, hypersexuality, and grandiose business plans.
Differential diagnosis
Major depressive disorder — No lifetime mania/hypomania; antidepressant monotherapy appropriate
Bipolar II disorder — Hypomania (>=4 days, no marked impairment, no psychosis, no hospitalization) plus MDE — never met full mania
Cyclothymic disorder — Chronic (>=2 years) subthreshold mood fluctuations not meeting MDE or hypomania criteria
Schizoaffective disorder — Psychotic symptoms >=2 weeks in the absence of mood symptoms
DSM-5-TR Bipolar I: At least one lifetime manic episode — distinct period (>=7 days, or any duration if hospitalized) of elevated/expansive/irritable mood AND increased goal-directed activity/energy, with >=3 DIG FAST symptoms (>=4 if mood is only irritable), causing marked impairment or psychotic features. The episode is not attributable to a substance or medical condition. MDE and hypomanic episodes are common but not required. Mood Disorder Questionnaire (MDQ) is a useful screening tool.
Labs
TSH, BMP, CBC, LFTs, urine drug screen, pregnancy test (women of reproductive age)
Lithium therapeutic range 0.6-1.2 mEq/L; toxicity >1.5 (tremor, ataxia, confusion); narrow therapeutic index — avoid NSAIDs, thiazides, ACEi (raise lithium).
Valproate teratogen — neural tube defects, autism, lower IQ. Contraceptive counseling essential; avoid in pregnancy and women of reproductive age unless no alternative.
Lamotrigine titration: increase no faster than every 2 weeks to prevent Stevens-Johnson syndrome.
Antidepressant-induced mania during treatment of an apparent unipolar depression is itself diagnostic of bipolar disorder.
Sleep deprivation reliably precipitates mania — sleep regularity is a core therapeutic target.
References
APA 2002 + guidance updates — American Psychiatric Association Practice Guideline for the Treatment of Patients with Bipolar Disorder, 2nd ed., with subsequent guidance
CANMAT/ISBD 2018 — Yatham LN et al. CANMAT and ISBD 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord 2018
DSM-5-TR — American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (2022)
BALANCE Trial — Geddes JR et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE). Lancet 2010
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