Bipolar I Disorder
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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Risk factors
- First-degree relative with bipolar disorder (10x population risk)
- Early-onset depression, postpartum onset, antidepressant-induced mania
- 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
- Substance/medication-induced — Stimulants, cocaine, corticosteroids, levodopa — symptoms resolve with discontinuation
- ADHD — Chronic, non-episodic; no euphoria, no decreased need for sleep, no grandiosity
- Borderline personality disorder — Mood reactivity in minutes-hours triggered by interpersonal events; chronic identity disturbance
- Hyperthyroidism — Tremor, tachycardia, weight loss, suppressed TSH
Diagnostic workup
Diagnostic criteria
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 baseline: BUN/Cr, TSH, calcium, ECG (age >40 or cardiac history)
- Valproate baseline: LFTs, CBC, pregnancy test
- Lamotrigine baseline: skin assessment
Imaging
- Neuroimaging not routine; consider MRI if atypical features or first episode after age 50
Diagnostic algorithm
| Episode | Duration | Severity Clue | Psychosis? |
|---|---|---|---|
| Mania (Bipolar I) | >=7 days (or any if hospitalized) | Marked impairment / hospitalization | Possible |
| Hypomania (Bipolar II) | >=4 days | No marked impairment | Never |
| Major depressive episode | >=2 weeks | Variable | Possible |
| Mixed features | Concurrent mania + depression sx | High suicide risk | Possible |
| Cyclothymia | >=2 years subthreshold | Chronic mood instability | No |
Treatment
First-line
- Mood stabilizer — lithium (gold standard, anti-suicide effect), valproate, or lamotrigine (bipolar depression and maintenance)
- Atypical antipsychotic — quetiapine, olanzapine, risperidone, aripiprazole, lurasidone, cariprazine
- Acute mania: lithium OR valproate + atypical antipsychotic; add benzodiazepine for agitation
- Bipolar depression: quetiapine, lurasidone, cariprazine, lumateperone, olanzapine-fluoxetine combination, or lamotrigine
- AVOID antidepressant monotherapy — risk of mania induction or rapid cycling
Acute mania (severe)
- Hospitalize if dangerous behavior, psychosis, or inability to care for self
- Lithium or valproate + atypical antipsychotic
- Short-course benzodiazepine for sleep restoration and agitation
- ECT for treatment-refractory mania, pregnancy, or catatonia
Maintenance
- Lithium first-line — unique anti-suicide effect demonstrated in meta-analyses
- Valproate alternative; avoid in pregnancy (neural tube defects, neurodevelopmental harm)
- Lamotrigine for predominant depressive polarity; titrate slowly to avoid Stevens-Johnson syndrome
- Psychoeducation, sleep regularity, substance use treatment, family-focused therapy
Bipolar depression
- Quetiapine, lurasidone, cariprazine, lumateperone monotherapy
- Olanzapine-fluoxetine combination
- Lamotrigine if depressive polarity predominates
- If antidepressant used, always with mood stabilizer cover and stop promptly after remission
Second-line / adjunct
- Carbamazepine, oxcarbazepine — alternative mood stabilizers
- Clozapine for treatment-resistant disease
- Combination therapy (lithium + valproate, lithium + atypical antipsychotic) for breakthrough episodes
- ECT for severe or pregnancy-related episodes
Complications
- Suicide — lifetime risk 10-15%; highest in mixed and depressive episodes
- Substance use disorders in ~40-60%
- Functional decline, occupational disability, marital instability
- Lithium: nephrogenic DI, chronic kidney disease, hypothyroidism, hyperparathyroidism
- Valproate: hepatotoxicity, pancreatitis, thrombocytopenia, polycystic ovaries, teratogenicity
- Metabolic syndrome from atypical antipsychotics
PANCE pearls
- 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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