A 32-year-old woman with bipolar I disorder presents with acute mania characterized by grandiosity, decreased need for sleep, and pressured speech. She has failed to respond to adequate trials of two atypical antipsychotics. Which mood stabilizer is the drug of choice for acute mania in this treatment-resistant case?

Explanation

## Drug of Choice for Acute Mania **Key Point:** Lithium carbonate remains the gold-standard mood stabilizer for acute mania, particularly when antipsychotics have failed or are contraindicated. It has the strongest evidence base and longest clinical track record in bipolar disorder. ## Mechanism & Clinical Efficacy Lithium's antimanic effect is thought to involve: - Inhibition of inositol monophosphatase (affecting phosphatidylinositol signalling) - Inhibition of glycogen synthase kinase-3β (GSK-3β), a key regulator of mood-relevant neurotransmitter systems - Modulation of monoamine neurotransmission **High-Yield:** Lithium has the most robust evidence for efficacy in acute mania (response rate 60–70%) and is superior for long-term maintenance and suicide prevention in bipolar disorder. ## Comparison with Other Mood Stabilizers | Feature | Lithium | Valproate | Carbamazepine | Lamotrigine | |---------|---------|-----------|---------------|-------------| | **Acute mania** | ★★★★★ | ★★★★ | ★★★ | ★ (poor) | | **Maintenance** | ★★★★★ | ★★★★ | ★★★ | ★★★★ | | **Depression** | ★★★ | ★★ | ★★ | ★★★★★ | | **Onset** | 5–7 days | 2–4 days | 3–7 days | Slow (weeks) | | **Narrow therapeutic index** | Yes (0.6–1.2 mEq/L) | No | No | No | **Clinical Pearl:** Valproate is faster-acting than lithium in acute mania but lacks lithium's superior long-term mood stabilization and anti-suicide benefits. Lamotrigine is ineffective for acute mania and is reserved for bipolar depression. ## Therapeutic Monitoring **Key Point:** Lithium requires: - Baseline renal function, thyroid function, and ECG - Serum levels checked 5 days after initiation, then at steady state (7–10 days) - Target level: 0.6–1.2 mEq/L for acute mania; 0.4–0.8 mEq/L for maintenance - Regular monitoring of renal and thyroid function (every 6–12 months) **Warning:** Lithium has a narrow therapeutic window. Toxicity (tremor, confusion, ataxia, seizures, cardiac arrhythmias) can occur at levels >1.5 mEq/L. Risk increases with dehydration, NSAIDs, ACE inhibitors, and thiazide diuretics.