FDA-Approved Second-Generation Antipsychotics for Mania in Bipolar Disorder
The FDA-approved second-generation antipsychotics (SGAs) for treating acute manic or mixed episodes in Bipolar I Disorder are aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone. 1, 2, 3
FDA-Approved SGAs for Bipolar Mania
Monotherapy Options
- Aripiprazole is FDA-approved for acute manic and mixed episodes in Bipolar I Disorder 1, 2
- Olanzapine is FDA-approved for acute manic and mixed episodes in Bipolar I Disorder 1, 2, 3
- Risperidone is FDA-approved for acute manic and mixed episodes in Bipolar I Disorder, with efficacy demonstrated in 3-week placebo-controlled trials 1, 2, 4
- Quetiapine is FDA-approved for acute manic episodes in Bipolar I Disorder 1, 2, 3
- Ziprasidone is FDA-approved for acute manic and mixed episodes in Bipolar I Disorder 1, 2
Adjunctive Therapy Options
- Risperidone is FDA-approved as adjunctive therapy with lithium or valproate for acute manic or mixed episodes in Bipolar I Disorder 4
- Quetiapine is also approved as adjunctive therapy with lithium or valproate 2, 5
Age-Specific Approvals
Adults
- All five SGAs (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) are FDA-approved for acute mania in adults 1, 2
Pediatric Population
- Risperidone is FDA-approved for treating acute manic or mixed episodes in children and adolescents ages 10-17 with Bipolar I Disorder 4
- Quetiapine is FDA-approved for treating mania in children and adolescents ages 10-17 with Bipolar I Disorder 5
- Aripiprazole is approved for pediatric bipolar mania 1, 2
Maintenance Treatment
- Olanzapine and aripiprazole are FDA-approved for maintenance treatment of Bipolar I Disorder 3, 6
- Quetiapine has shown efficacy in maintenance treatment, particularly when used as adjunctive therapy with lithium or valproate 6
Clinical Considerations
Efficacy Comparisons
- Meta-analyses suggest that olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole have similar antimanic efficacy 3
- Selection should be guided by safety profile, tolerability, and individual patient factors 3, 7
Safety Considerations
- Metabolic effects (weight gain, type 2 diabetes, dyslipidemia) vary among SGAs, with olanzapine generally having higher risk 3
- Regular monitoring for metabolic side effects is essential, particularly with atypical antipsychotics 1
- Baseline assessments should include body mass index, waist circumference, blood pressure, fasting glucose, and lipid panel 8
Common Pitfalls to Avoid
- Using antidepressant monotherapy in bipolar disorder, which may trigger manic episodes or rapid cycling 1, 2
- Inadequate duration of maintenance therapy, which can lead to high relapse rates 1
- Failure to monitor for metabolic side effects of SGAs 1, 8
- Overlooking comorbidities that may complicate treatment 1
Special Populations
- For women of childbearing potential, valproate should be avoided when possible due to teratogenic risk 8
- In adolescents, lithium is the only FDA-approved agent for bipolar disorder in patients age 12 and older, though SGAs are commonly used 1, 8
The selection of a specific SGA should be based on the patient's symptom profile, previous response to medication, side effect profile, and comorbid conditions, with careful monitoring for both efficacy and adverse effects.