What is the best medication to treat a patient with bipolar disorder, characterized by manic episodes with excitement, hyperactivity, impulsivity, disinhibition, aggression, and decreased need for sleep, followed by severe depression?

Lithium is the Best Treatment for Bipolar Disorder

Lithium is the optimal medication for this patient presenting with classic bipolar disorder symptoms (manic episodes with excitement, hyperactivity, impulsivity, disinhibition, aggression, decreased need for sleep, followed by severe depression). 1, 2

Why Lithium is the Clear Choice

Lithium is the only FDA-approved medication that treats both acute mania AND provides maintenance therapy to prevent both manic and depressive episodes in bipolar disorder. 2 The FDA label explicitly states that lithium is indicated for manic episodes of Bipolar Disorder and as maintenance treatment to reduce the frequency and intensity of episodes. 2

Superior Evidence Base

• Lithium has more evidence for prophylaxis of bipolar episodes than any other agent, making it the gold standard for long-term management. 3, 4
• Lithium is the only drug effective in preventing manic, depressive, AND suicidal symptoms, a unique profile not shared by other mood stabilizers. 4
• The American Academy of Child and Adolescent Psychiatry recommends lithium as first-line treatment for both acute mania and maintenance therapy, with superior evidence for long-term efficacy compared to alternatives. 1

Clinical Efficacy

• Response rates for lithium in acute mania range from 38-62%, with symptom normalization typically occurring within 1-3 weeks. 1, 2
• Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties. 1
• For maintenance therapy, lithium significantly reduces both the frequency and intensity of mood episodes. 2, 4

Why the Other Options Are Incorrect

• Diazepam (benzodiazepine): Only treats acute anxiety/agitation symptoms, has no mood-stabilizing properties, and carries risks of tolerance, dependence, and paradoxical agitation. 1
• Modafinil (wakefulness-promoting agent): Used for narcolepsy/sleep disorders, not bipolar disorder, and could potentially worsen manic symptoms. [General Medicine Knowledge]
• Pentobarbital (barbiturate): Sedative with no mood-stabilizing properties, high abuse potential, and dangerous in overdose. [General Medicine Knowledge]
• Selegiline (MAO-B inhibitor): Used for Parkinson's disease and depression, not indicated for bipolar disorder and could trigger mania. [General Medicine Knowledge]

Practical Implementation

Dosing Strategy

• For acute mania: Start with 600 mg three times daily (1800 mg/day total), targeting serum levels of 1.0-1.5 mEq/L. 2
• For maintenance therapy: Typically 300 mg three times or four times daily, targeting serum levels of 0.6-1.2 mEq/L. 2
• Draw lithium levels 8-12 hours after the previous dose for accurate measurement. 2

Monitoring Requirements

• During acute phase: Check serum lithium levels twice weekly until stable. 2
• During maintenance: Monitor lithium levels, renal function, and thyroid function every 3-6 months. 1
• Baseline assessment should include complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females. 1

Critical Clinical Considerations

• Elderly patients often require reduced doses and may exhibit toxicity at levels normally tolerated by younger patients. 2
• Maintenance therapy must continue for at least 12-24 months after stabilization; premature discontinuation leads to >90% relapse rates. 1
• Lithium withdrawal is associated with dramatically increased relapse risk, especially within 6 months of discontinuation. 1
• Some patients will require lifelong therapy when benefits outweigh risks. 1

Common Pitfalls to Avoid

• Do not rely solely on serum levels—accurate patient evaluation requires both clinical assessment and laboratory analysis. 2
• Avoid antidepressant monotherapy for the depressive episodes, as this can trigger mania or rapid cycling; always combine with a mood stabilizer like lithium. 1
• Do not discontinue lithium prematurely during maintenance phase, as this is associated with relapse rates exceeding 90% in noncompliant patients. 1
• Monitor for lithium toxicity, especially with dehydration, NSAIDs, ACE inhibitors, or thiazide diuretics that can increase lithium levels. [General Medicine Knowledge]