Comparative efficacy and acceptability of combined antipsychotics and mood stabilizers versus individual drug classes for acute mania: Network meta-analysis

Objectives: Recent network meta-analyses of drug treatments for acute mania have only evaluated the efficacy and acceptability of individual drug treatments. The relative efficacy and acceptability of combined drug treatment has not been assessed. Methods: Double-blind drug trials in acute mania were identified using a systematic search strategy. We recorded numbers of patients enrolled, endpoints for efficacy (changes in mania rating scales, numbers of responders) and acceptability (numbers of dropouts) and treatment administered (categorized as antipsychotic, mood stabilizer, combined antipsychotic/mood stabilizer or placebo). Data were analyzed using a random effects frequentist network meta-analysis. Results: All three drug categories were more effective than placebo. Antipsychotics and combined antipsychotic/mood stabilizer were significantly more effective than mood stabilizers for changes in mania rating scales. Combined antipsychotic/mood stabilizer was significantly more effective than mood stabilizers and antipsychotics for responder rate. Dropout rates were significantly lower for antipsychotics compared with placebo and mood stabilizers. Combined antipsychotic/mood stabilizer had the highest probability of being the best treatment based on change in mania rating scales (96.1% for all mania scales; 85.5% for Young Mania Rating Scale), and 99.3% for being the best treatment for responders. Antipsychotics had 82.0% probability as the best treatment to minimize dropouts. Conclusion: Combined antipsychotic/mood stabilizer appears to have efficacy advantages over antipsychotic or mood stabilizer monotherapy in acute mania, and should be considered as first line therapy.