What are the FDA-approved medications for treating mania?

FDA-Approved Medications for Mania

The FDA has approved lithium, valproate (divalproex), and five atypical antipsychotics—olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole—for the treatment of acute mania in bipolar disorder. 1, 2

Complete List of FDA-Approved Agents

Mood Stabilizers

• Lithium was the first FDA-approved medication for bipolar disorder in 1970, approved for both acute mania and maintenance therapy in patients age 12 and older 1, 2
• Divalproex (valproate) received FDA approval for acute mania in 1994 2

Atypical Antipsychotics

• Olanzapine was approved in 2000 as the first atypical antipsychotic for acute mania, and remains the only atypical antipsychotic approved for maintenance therapy to prevent relapse 3, 2
• Risperidone received FDA approval for acute mania in 2003 2, 4
• Quetiapine was approved in 2004 for acute manic episodes 2, 4
• Ziprasidone gained FDA approval in 2004 for acute mania 2, 4
• Aripiprazole was approved in 2004 for the treatment of acute mania 2, 4

Traditional Antipsychotic

• Chlorpromazine (a typical antipsychotic) was approved for bipolar disorder in 1973, though it is rarely used as first-line therapy today due to inferior tolerability and higher extrapyramidal symptom risk 2, 1

Clinical Algorithm for Medication Selection

For Acute Mania Monotherapy

• Start with lithium, valproate, or an atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine, or ziprasidone) based on individual patient factors 1
• Atypical antipsychotics provide more rapid symptom control than mood stabilizers alone, making them preferable when immediate behavioral control is needed 1, 5
• Aripiprazole offers a favorable metabolic profile compared to olanzapine, making it preferable when metabolic concerns exist 1

For Severe or Treatment-Resistant Mania

• Combination therapy with a mood stabilizer (lithium or valproate) plus an atypical antipsychotic is the first-line approach for severe presentations and treatment-resistant cases 1, 5
• This combination is generally well-tolerated and provides superior efficacy compared to monotherapy 5, 3

For Maintenance Therapy

• Lithium shows superior evidence for long-term efficacy in preventing both manic and depressive episodes 1
• Olanzapine is currently the only atypical antipsychotic with FDA approval for maintenance therapy to prevent relapse 3
• Continue the regimen that effectively treated the acute episode for at least 12-24 months 1

Important Clinical Considerations

Efficacy Differences

• Response rates for lithium range from 38-62% in acute mania 1
• Valproate demonstrates higher response rates (53%) compared to lithium (38%) in children and adolescents with mania and mixed episodes 1
• Atypical antipsychotics demonstrate efficacy across a broader range of symptoms than typical antipsychotics and may possess mood-stabilizing properties 5

Tolerability Profiles

• Atypical antipsychotics have superior neurological tolerability compared to typical antipsychotics, with lower rates of extrapyramidal symptoms 5, 4
• Olanzapine is associated with higher incidence of weight gain than most atypical agents, though it has low incidence of extrapyramidal symptoms 3
• Individual atypical agents differ in their propensity to cause weight gain and metabolic side effects, requiring careful monitoring 5

Common Pitfalls to Avoid

• Never use antidepressant monotherapy, as this can trigger manic episodes or rapid cycling 1
• Avoid inadequate trial duration—systematic medication trials require 6-8 weeks at adequate doses before concluding an agent is ineffective 1
• Do not overlook the need for regular metabolic monitoring with atypical antipsychotics, particularly for weight gain, glucose, and lipid abnormalities 1
• Typical antipsychotics like haloperidol should not be used as first-line alternatives due to inferior tolerability and higher extrapyramidal symptom risk 1