Clozapine in bipolar disorder: A systematic review and meta-analysis

Objectives: To assess the clinical efficacy of clozapine in bipolar disorder and its adverse effect profile. Methods: A literature search with no year and no language restriction was conducted. The search yielded 3858 articles, with 2453 remaining after duplicate removal; 9 were suitable for the systematic review. From the 9 included studies, 3 (100 patients treated with clozapine and 102 patients treated with other antipsychotics) could be included in a meta-analysis to test clozapine efficacy in the treatment of manic episodes. Results: Clozapine's efficacy was similar to other antipsychotics (Mean difference (MD): 0.03 [95%CI: 0.86-0.92], p = 0.59) in manic episodes. The systematic review also suggested that clozapine is faster at improving symptoms in manic episodes. In addition, two studies included patients with treatment resistant bipolar disorder (TRBD) and showed that clozapine is superior to other treatments for this specific population. Sedation was the most frequent side effect (49.6%), followed by constipation (31.8%) and tachycardia (23.2%). Conclusion: Clozapine's efficacy was similar to other antipsychotics in manic episodes and is superior to other antipsychotics among TRBD patients.