Acute bipolar mania: a systematic review and meta‐analysis of co‐therapy vs. monotherapy

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Abstract
Introduction: The aim of this meta‐analysis was to systematically review the effectiveness of co‐therapy compared with monotherapy for people with bipolar mania. Method: MEDLINE, Embase, Psychinfo, The Cochrane Library and reference lists of retrieved studies were searched without language restrictions for randomized controlled trials evaluating co‐therapy compared with monotherapy for acute bipolar mania. Each trial was assessed for susceptibility to bias. Data on mania outcomes, withdrawals, extrapyramidal symptoms and weight were extracted and pooled effect estimates summarized as relative risks (RR) or differences in mean values (MD) where appropriate. Results: Eight eligible studies were included (1124 participants). Significant reductions in mania (Young Mania Rating Scale, YMRS) scores were shown for haloperidol, olanzapine, risperidone and quetiapine as co‐therapy compared with monotherapy with a mood stabilizer. For atypical antipsychotics combined, the pooled difference in mean scores was 4.41 (95% CI: 2.74, 6.07). Significantly more participants on co‐therapy met the response criterion (at least 50% reduction in YMRS score), RR 1.53 (1.31, 1.80). With some drugs, co‐therapy decreased tolerability compared with monotherapy, and resulted in greater weight gain. There were insufficient data to compare one co‐therapy regimen with another. Conclusion: The addition of antipsychotic treatment to established mood‐stabilizer treatment is more effective than mood‐stabilizer treatment alone.