Notes · Psychiatry · 30 October 2026

Bipolar disorder – diagnosis and management

Definition

• Bipolar disorder (BD) is a chronic mood disorder characterised by recurrent episodes of abnormally elevated (mania/hypomania) and depressed mood, often interspersed with periods of euthymia (normal mood).
• The term “bipolar” reflects the two poles of mood disturbance: mania (or hypomania) and depression.

Epidemiology

• Lifetime prevalence of BD worldwide is about 1–2 % (≈1.5 % in most epidemiological surveys).
• The disorder has a roughly equal gender distribution, although women are slightly more prone to rapid cycling and mixed states.
• Onset typically occurs in late adolescence or early adulthood, with a mean age of first episode around 20 years.
• Family history is a strong risk factor; first‑degree relatives have a 10‑fold increased risk compared with the general population.

Aetiology

• Genetic factors: Heritability estimates range from 60–80 %; multiple susceptibility loci have been identified (e.g., CACNA1C, ANK3).
• Neurobiological factors: Dysregulation of monoamine neurotransmitters (dopamine, serotonin, norepinephrine), altered glutamatergic signaling, and abnormalities in intracellular calcium channels.
• Neuroanatomical changes: Reduced volume of prefrontal cortex and amygdala hyper‑reactivity on functional imaging.
• Environmental triggers: Childhood trauma, substance misuse (especially cannabis and stimulants), sleep deprivation, and stressful life events can precipitate episodes.

Pathophysiology (step‑by‑step)

1. Genetic predisposition leads to altered expression of ion channel and neurotransmitter‑related genes.
2. Neurotransmitter imbalance results in excessive dopaminergic activity during mania and reduced serotonergic/noradrenergic tone during depression.
3. Neurocircuitry dysfunction: Hyperactive limbic system (amygdala) drives emotional reactivity, while hypoactive prefrontal regulatory circuits fail to inhibit mood swings.
4. Neuroendocrine dysregulation: Abnormal hypothalamic‑pituitary‑adrenal (HPA) axis activity contributes to stress‑related mood destabilisation.
5. Neuroinflammation and oxidative stress have been implicated in progressive brain changes and cognitive deficits observed in chronic BD.

Clinical Features

Manic Episode (per DSM‑5)

• Abnormally elevated, expansive, or irritable mood lasting ≥1 day (hospitalisation required) or ≥4 days (outpatient).
• At least three (or four if mood is only irritable) of the following: inflated self‑esteem, decreased need for sleep, pressured speech, flight of ideas, distractibility, increase in goal‑directed activity, risky behaviour (e.g., spending sprees).

Hypomanic Episode

• Same symptom cluster as mania but duration ≥4 days, no marked functional impairment, and no psychotic features.

Depressive Episode

• Depressed mood or anhedonia (loss of interest) for ≥2 weeks, plus ≥5 of: weight change, sleep disturbance, psychomotor agitation/retardation, fatigue, feelings of worthlessness/guilt, diminished concentration, recurrent thoughts of death.

Mixed Features

• Simultaneous presence of ≥3 depressive symptoms during a manic/hypomanic episode, or vice‑versa.

Course Patterns

• Type I BD: At least one manic episode (may have depressive episodes).
• Type II BD: At least one hypomanic episode and one major depressive episode, never a full manic episode.
• Cyclothymia: Chronic fluctuating mood with numerous hypomanic and depressive symptoms that do not meet full episode criteria.

Investigations

Management (Current Guidelines – NICE 2023, APA 2023, Indian Psychiatric Society 2022)

Acute Mania

• First‑line: Lithium (target serum level 0.8–1.2 mmol/L) or atypical antipsychotic (e.g., risperidone 2–6 mg/day, olanzapine 10–20 mg/day, quetiapine 400–800 mg/day).
• Second‑line: Valproate (serum level 50–100 µg/mL) or carbamazepine (4–12 µg/mL).
• Adjunctive: Benzodiazepines (lorazepam 1–2 mg q6h PRN) for severe agitation.

Acute Depressive Episode

• First‑line: Lithium or lamotrigine (starting 25 mg/day, titrating to 200 mg/day) – effective for depressive polarity.
• Second‑line: Quetiapine 300 mg/day or lurasidone 20–60 mg/day.
• Avoid: Antidepressant monotherapy due to risk of switching to mania; if needed, combine with mood stabiliser.

Maintenance/Prophylaxis

• Lithium remains gold standard (reduces suicide risk). Target serum 0.6–0.8 mmol/L for prophylaxis.
• Lamotrigine preferred for patients with predominant depressive episodes.
• Atypical antipsychotics (e.g., aripiprazole, olanzapine, risperidone) are useful when lithium is contraindicated or not tolerated.
• Psychosocial interventions: Psycho‑education, cognitive‑behavioural therapy (CBT), family‑focused therapy, and regular sleep‑wake scheduling.

Monitoring

• Lithium: Serum level every 3 months after stabilization; check renal function (eGFR) and thyroid (TSH) every 6 months.
• Valproate: Liver enzymes and platelet count every 3 months.
• Atypical antipsychotics: Metabolic monitoring (weight, BMI, fasting glucose, lipids) quarterly.

Special Populations

• Pregnancy: Avoid valproate and carbamazepine (teratogenic). Lithium can be continued with close monitoring; switch to haloperidol if severe mania.
• Elderly: Start low, go slow; prefer atypical antipsychotics with lower anticholinergic burden.

Complications

• Suicide: Lifetime risk up to 15 %; highest during depressive or mixed states.
• Medical comorbidities: Cardiovascular disease, diabetes, obesity, and metabolic syndrome (often medication‑related).
• Neurocognitive decline: Impaired executive function, memory deficits, especially with repeated episodes.
• Substance use disorder: High prevalence; worsens prognosis.
• Medication toxicity: Lithium toxicity (≥1.5 mmol/L) can cause tremor, ataxia, renal impairment; valproate hepatotoxicity; antipsychotic‑induced tardive dyskinesia.

High‑Yield Exam Points

• Diagnostic criteria: Remember the minimum duration for mania (1 day inpatient, 7 days outpatient) and hypomania (4 days).
• Lithium: Gold‑standard mood stabiliser; reduces suicide; therapeutic range 0.6–1.2 mmol/L; monitor renal & thyroid function.
• Distinguish Type I vs Type II: Presence of full mania = Type I; hypomania + depression = Type II.
• Mixed features: ≥3 depressive symptoms during a manic episode (or vice‑versa); treat with mood stabiliser + atypical antipsychotic, avoid antidepressant monotherapy.
• Rapid cycling: ≥4 mood episodes in 12 months; often requires combination therapy (e.g., lithium + valproate) and careful monitoring.
• Pregnancy considerations: Valproate contraindicated; lithium may be used with caution; avoid carbamazepine if possible.
• First‑line acute mania: Lithium or atypical antipsychotic; if severe, combine both.
• First‑line acute depression: Lithium or lamotrigine; avoid antidepressant monotherapy.
• Metabolic monitoring: Essential for all patients on atypical antipsychotics (weight, glucose, lipids).

Practice questions

1. A 24‑year‑old man presents with a 6‑day history of elevated mood, decreased need for sleep, pressured speech, and spending sprees. He has no psychotic symptoms. Which DSM‑5 diagnosis best fits?
Answer: Hypomanic episode — duration ≥4 days, ≥3 symptoms, no marked functional impairment, and no psychosis.

2. Which mood stabiliser is most strongly associated with a reduction in suicide risk in bipolar disorder?
Answer: Lithium — meta‑analyses show a significant suicide‑protective effect compared with other agents.

3. A pregnant woman with bipolar I disorder experiences a severe manic episode. Which medication is preferred according to current guidelines?
Answer: Haloperidol — safe in pregnancy and effective for acute mania when lithium is contraindicated.

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