What is the treatment for bipolar disorder (manic depression)?

Treatment of Bipolar Disorder (Manic Depression)

For acute mania, start with lithium, valproate, or an atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine) as first-line monotherapy, with lithium being the only FDA-approved agent for patients age 12 and older. 1, 2

Acute Mania/Mixed Episodes

First-line medication options:

• Lithium 5-10 mg once daily (adults) or 2.5-5 mg once daily (adolescents), targeting 10 mg/day within several days 3
• Valproate with systematic 6-8 week trial using adequate doses before considering changes 1
• Atypical antipsychotics (olanzapine 10-15 mg daily, risperidone, quetiapine, aripiprazole, ziprasidone) provide more rapid symptom control than mood stabilizers alone 1, 3

Response rates favor valproate (53%) over lithium (38%) in children and adolescents with mania and mixed episodes, though lithium remains the only FDA-approved option for ages 12+ 1, 4, 2

For severe presentations, combine lithium or valproate with an atypical antipsychotic rather than continuing monotherapy 1

Maintenance Therapy

Continue the regimen that successfully treated the acute episode for at least 12-24 months, with some patients requiring lifelong treatment 1, 4

Lithium demonstrates superior evidence for preventing both manic and depressive episodes in long-term trials 1

Critical pitfall: Withdrawal of maintenance lithium increases relapse risk dramatically, especially within 6 months of discontinuation, with >90% of non-compliant adolescents relapsing compared to 37.5% of compliant patients 1, 4

Bipolar Depression

Start with olanzapine-fluoxetine combination (5 mg olanzapine + 20 mg fluoxetine daily in adults; 2.5 mg olanzapine + 20 mg fluoxetine in adolescents) as first-line treatment 1, 4, 3

Never use antidepressant monotherapy—this triggers manic episodes, rapid cycling, and mood destabilization 1, 4, 5

Lamotrigine is particularly effective for preventing depressive episodes during maintenance, though it requires slow titration to minimize risk of Stevens-Johnson syndrome 1, 4

Required Monitoring

For lithium:

• Baseline: Complete blood count, electrolytes, blood urea nitrogen, creatinine, serum calcium, thyroid function, urinalysis, pregnancy test in females 6
• Ongoing: Lithium levels, renal and thyroid function, urinalysis every 3-6 months 6, 1

For valproate:

• Baseline: Liver function tests, complete blood count, pregnancy test 6, 7
• Ongoing: Serum drug levels, hepatic and hematological indices every 3-6 months 6, 7

For atypical antipsychotics:

• Baseline: Body mass index, waist circumference, blood pressure, fasting glucose, fasting lipid panel 6
• Ongoing: Body mass index monthly for 3 months then quarterly; blood pressure, fasting glucose, lipids at 3 months then yearly 6, 1
• Monitor for extrapyramidal side effects and tardive dyskinesia 6

Psychosocial Interventions

Combine pharmacotherapy with psychoeducation, cognitive-behavioral therapy, and family interventions—medication alone provides only partial relief with high recurrence rates 6, 1, 8

Psychotherapy added to medication consistently shows advantages over medication alone for symptom burden and relapse prevention 8

Electroconvulsive Therapy

For severely impaired adolescents with bipolar I disorder who fail medication trials or cannot tolerate them, consider ECT 6, 4

ECT is the treatment of choice during pregnancy, for catatonia, neuroleptic malignant syndrome, or when standard medications are contraindicated 6

Critical Pitfalls to Avoid

Inadequate trial duration: Complete 6-8 weeks at adequate doses before changing medications 1, 7

Premature discontinuation of maintenance therapy: This dramatically increases relapse risk, particularly with lithium withdrawal 1, 4

Failure to monitor metabolic parameters with atypical antipsychotics: Weight gain, diabetes, and hyperlipidemia develop frequently and require systematic tracking 6, 1, 4

Overlooking comorbidities: Screen for substance use disorders, anxiety disorders, and ADHD, which complicate treatment and require specific management once mood is stabilized 1, 4

Using antidepressants without mood stabilizers: This is contraindicated and triggers mood destabilization 1, 4, 5