Long-acting injectable antipsychotics for prevention of relapse in bipolar disorder: A systematic review and meta-analyses of randomized controlled trials

Abstract

Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n = 1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials) = 449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents = 283]; and placebo = 284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio = 0.63, P < .0001), relapse of manic symptoms (risk ratio = 0.42, P < .00001), and all-cause discontinuation (risk ratio = 0.75, P = .007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio = 4.82, P = .001) and weight gain (risk ratio = 3.80,