Journal of Psychiatry Spectrum (Jan 2025)
Efficacy and Tolerability of Cariprazine as Monotherapy for Acute Bipolar Depression: A Systematic Review and Meta-analysis
Abstract
Background: Bipolar depression (BDep) presents a significant clinical challenge with limited treatment options. The second-generation antipsychotics are increasingly utilized as primary or adjunct treatments. The use of cariprazine as monotherapy was approved by the US- Food and Drug Administration for acute BDep in 2019. Aim: The aim of this study is to evaluate the efficacy and tolerability of cariprazine as monotherapy for acute BDep compared to placebo. Methods: We conducted a systematic review of randomized placebo-controlled trials assessing cariprazine as monotherapy for acute BDep. The inclusion criteria encompassed English language studies comparing cariprazine as monotherapy to placebo, with outcomes measured within 6–12 weeks. The primary outcome measures included response and remission rates. The secondary outcomes included standardized mean differences (SMDs) in Montgomery Åsberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Depression (HAM-D) score changes from baseline to endpoint, dropout rates, and dropout rates due to adverse effects. The binary and continuous outcomes were analyzed using the Mantel–Haenszel and inverse variance methods, respectively, with RevMan 5.4 software. This study was done as the part of a network meta-analysis registered with PROSPERO (CRD42017077575). Results: Only four studies were eligible for the meta-analysis, encompassing 1747 patients. Cariprazine demonstrated significantly higher response rates (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.18–1.79) and remission rates (OR = 1.52, 95% CI: 1.20–1.93) compared to placebo. SMDs showed that cariprazine was more efficacious (MADRS: SMD −0.24, 95% CI: −0.34 to −0.14, and HAM-D: SMD −0.21, 95% CI: −0.31 to −0.11). There was no significant difference in overall dropout rates and dropout rates due to adverse effects between cariprazine and the placebo arm. Hence, tolerability was comparable to placebo. Heterogeneity was not significant (I2 = 0). Conclusion: Cariprazine monotherapy was found to be efficacious in acute BDep, with a significant number of patients attaining remission. It is comparable to a placebo in terms of tolerability profile. Future studies are required to understand its efficacy and safety as a prophylactic for preventing mood episodes in BDep.
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