Psychiatry · Mood Disorders
The facts most likely to be tested
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Bipolar disorder has the greatest genetic linkage of any psychiatric illness, with onset typically in young adults.
Bipolar I requires a manic episode lasting >= 1 week (or any duration if hospitalization is required) with elevated/irritable mood, grandiosity, decreased need for sleep, pressured speech, and risky behavior.
Always exclude substance-induced mania with a urine drug screen for cocaine and amphetamines before diagnosis.
Lithium is the single best answer to most bipolar questions and uniquely reduces suicide risk.
Acute mania is treated with lithium, valproic acid, or an atypical antipsychotic; atypicals (olanzapine) are preferred for rapid control of severe agitation.
Bipolar depression uses lithium, quetiapine, lurasidone, or lamotrigine; avoid lithium with renal impairment and watch lamotrigine for Stevens-Johnson syndrome.
Hypomania (bipolar II) is briefer, less severe, and not functionally impairing, distinguishing it from full mania.
Vignette unlocked
A 21-year-old college student is brought in by his roommates after a week of unusual behavior. He has not slept in four days, talks rapidly and is difficult to interrupt, claims he will revolutionize physics, and has run up thousands of dollars in credit card charges. He is irritable and has had multiple new sexual partners this week. A urine drug screen is negative.
Which of the following is the most appropriate first-line treatment?
Lithium
A manic episode lasting at least one week with grandiosity, decreased need for sleep, pressured speech, and risky behavior, after excluding substance use, confirms bipolar I disorder. Lithium is the single best answer for most bipolar questions and additionally reduces suicide risk.
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High yield triage
Etiology / Epidemiology
Mood disorder with the greatest genetic linkage of any psychiatric illness; onset typically in young adults.
Clinical Manifestations
Mania >=1 week (elevated mood, grandiosity, decreased need for sleep, pressured speech, risky behavior); often begins with depression.
Diagnosis
Clinical; always exclude cocaine/amphetamine use with urine drug screen before diagnosis.
Treatment
Lithium is the answer to most bipolar questions; acute mania uses lithium, valproate, or atypical antipsychotics.
Prognosis
Chronic and recurrent with high suicide risk; lithium reduces suicidality.
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Epidemiology & Etiology
Bipolar disorder is a recurrent mood disorder that is regarded as the psychiatric illness with the greatest genetic linkage, with high heritability and frequent family history. It typically presents in young adults and is associated with increased central norepinephrine and dopamine activity. The illness often begins with a depressive episode plus paradoxically increased energy and decreased sleep, which can delay correct diagnosis. Cocaine and amphetamine use can precipitate or mimic mania, so substance use must always be considered.
Pertinent Anatomy
Bipolar disorder involves dysregulation of monoaminergic circuits linking the prefrontal cortex, limbic system (amygdala), and basal ganglia that govern mood and reward. Manic states are associated with excessive central norepinephrine and serotonin and dopaminergic signaling, while depressive phases reflect monoamine deficiency. Mood stabilizers such as lithium act on intracellular second-messenger systems (inositol and glycogen synthase kinase-3) within these neurons.
Pathophysiology
The disorder reflects unstable regulation of monoamine neurotransmission across limbic-cortical circuits, producing oscillation between pathologically elevated and depressed mood states. Mania is characterized by excess norepinephrine and serotonin with heightened dopaminergic reward drive, explaining grandiosity, impulsivity, and decreased need for sleep, whereas the depressive pole mirrors the monoamine deficiency of major depression. Lithium and anticonvulsant mood stabilizers are thought to dampen this neuronal hyperexcitability and stabilize signal-transduction pathways.
Clinical Manifestations
The hallmark is a manic episode lasting at least 1 week with abnormally elevated or irritable mood plus symptoms such as inflated self-esteem/grandiosity, decreased need for sleep, pressured speech, racing thoughts, distractibility, increased goal-directed activity, and excessive involvement in pleasurable risky activities (spending sprees, hypersexuality). A classic vignette is a young college student talking fast, giggling, sleepless for days, drinking heavily, and having numerous sexual contacts. Mania severely impairs functioning and may warrant hospitalization, whereas hypomania (bipolar II) is briefer, less severe, and not impairing. Episodes alternate with major depression.
Diagnosis
Bipolar I is diagnosed clinically by a history of at least one manic episode (>=1 week, or any duration if hospitalization is required); bipolar II requires hypomania plus major depression without full mania. Before making the diagnosis, always rule out substance-induced mood disorder by history and a urine drug screen for cocaine and amphetamines. The distinction between mania and hypomania rests on severity, functional impairment, and duration. Cyclothymia involves >=2 years of hypomanic symptoms and mild depression.
Treatment
Distinguish acute mania from bipolar depression. For acute mania, use lithium, valproic acid, or an atypical antipsychotic; in severe agitation, atypical antipsychotics (e.g., olanzapine) are preferred for their rapid onset. For bipolar depression, use lithium, quetiapine, lurasidone, or lamotrigine; lurasidone is relatively safe in pregnancy. Lithium is the single best answer to most bipolar questions and reduces suicide risk, but avoid lithium if renal function is compromised. Monitor lithium levels (toxicity: confusion, ataxia, tremor) and valproate (hepatotoxicity, teratogenicity); lamotrigine carries a risk of Stevens-Johnson syndrome.
Prognosis
Bipolar disorder is a chronic, recurrent illness with episodes that tend to become more frequent over time without maintenance therapy. It carries a high lifetime risk of suicide, and lithium uniquely reduces suicidality. Long-term adherence to mood stabilizers improves the course, but nonadherence, comorbid substance use, and rapid cycling worsen outcomes. Antidepressant monotherapy should be avoided as it can precipitate a manic switch.
Differential Diagnosis
Major Depression with Psychotic Features: depression and psychosis occur together without any history of mania; presence of a prior manic episode defines bipolar.
Substance-induced mood disorder: cocaine or amphetamine intoxication mimics mania; urine drug screen positive and symptoms resolve with abstinence.
Schizoaffective Disorder: psychotic symptoms persist for >=2 weeks in the absence of a mood episode, unlike bipolar where psychosis is confined to mood episodes.
Cyclothymic Disorder: >=2 years of fluctuating hypomanic and mild depressive symptoms that never meet full criteria for mania or major depression.
Borderline Personality Disorder: mood lability is rapid (hours-days) and reactive to interpersonal stress rather than sustained episodes lasting days to weeks.