Treatment of Acute Mania in Adults
For acute mania in adults, the recommended first-line treatment is monotherapy with lithium, valproate, or an atypical antipsychotic such as risperidone or aripiprazole, with aripiprazole being preferred due to its efficacy and lower risk of weight gain. 1
Treatment Algorithm Based on Mania Severity
Mild to Moderate Mania Without Psychotic Features
- First-line: Monotherapy with one of the following:
- Lithium
- Valproate
- Atypical antipsychotic (risperidone 1-6 mg/day or aripiprazole 1-6 mg/day)
Aripiprazole is particularly recommended due to its efficacy and more favorable metabolic profile 1. Clinical trials have demonstrated that risperidone at doses of 1-6 mg/day is effective for acute manic episodes, with mean modal doses of 4.1-5.6 mg/day showing superiority to placebo in reducing Young Mania Rating Scale (YMRS) scores 2.
Severe Mania, Psychotic Features, or Rapid Cycling
- First-line: Combination therapy with:
- Mood stabilizer (lithium or valproate) + atypical antipsychotic
The FDA has approved risperidone as adjunctive therapy with lithium or valproate for acute manic episodes associated with Bipolar I Disorder 2. This combination has demonstrated superior efficacy compared to mood stabilizer monotherapy in controlled trials.
Special Clinical Considerations
For Psychotic Mania
- Prioritize: Antipsychotics (risperidone or aripiprazole)
- Risperidone has demonstrated efficacy at doses of 1-6 mg/day for acute manic episodes with psychotic features 2
For Mixed Episodes or Rapid Cycling
- Preferred: Valproate over lithium
- Consider combination therapy with an atypical antipsychotic
For Agitation and Sleep Disturbances
- Short-term benzodiazepines may be used as adjunctive treatment
- Once stabilized, cognitive behavioral therapy for insomnia (CBT-I) is recommended for ongoing sleep issues 1
Medication Dosing and Administration
Risperidone
- Starting dose: 2-3 mg/day
- Target dose: 1-6 mg/day (mean modal dose in clinical trials: 4.1-5.6 mg/day)
- Demonstrated efficacy in 3-week placebo-controlled trials 2
Aripiprazole
- Starting dose: 15 mg/day
- Target dose: 15-30 mg/day
- Shown to be effective in reducing manic symptoms within 3-4 weeks 3
Valproate
- Consider loading dose strategy for rapid response
- Target blood level: 50-125 μg/mL
- Intravenous loading may be considered in severe cases for rapid stabilization 4
Monitoring Requirements
Regular monitoring is essential to minimize side effects:
Baseline assessments:
- Serum levels (for lithium/valproate)
- Liver function tests
- Complete blood count
- Thyroid function
- Renal function
- Pregnancy tests (females of childbearing potential)
- Weight/BMI
- Blood pressure
- Fasting glucose
- Lipid panel
Follow-up monitoring:
- BMI: Monthly for first 3 months, then quarterly
- Blood pressure, glucose, lipids: After 3 months, then yearly
- Serum drug levels, hepatic function, hematological indices: Every 3-6 months 1
Common Pitfalls and Caveats
Medication side effects:
- Atypical antipsychotics can cause movement disorders (akathisia, extrapyramidal symptoms)
- Aripiprazole causes more movement disorders than placebo but fewer than haloperidol at 12 weeks 3
- Valproate carries risks of gastrointestinal disorders, hepatitis, pancreatitis, and potential development of polycystic ovary disease in females 1
Treatment resistance:
- If monotherapy fails, switch to combination therapy
- Consider electroconvulsive therapy for treatment-resistant cases
Maintenance considerations:
- Treatment should continue for at least 2 years after the last episode
- Abrupt discontinuation can lead to withdrawal symptoms and rapid relapse
- Use a gradual tapering approach when discontinuing 1
Medication interactions:
- Monitor for interactions between mood stabilizers and other medications
- Adjust dosages accordingly when using combination therapy
The evidence strongly supports the use of atypical antipsychotics like risperidone and aripiprazole for acute mania, with multiple studies demonstrating their effectiveness in reducing symptoms 1, 2, 3. While older treatments like lithium remain effective, newer options provide additional benefits in terms of rapid onset and specific symptom targeting.