Second-Generation Antipsychotics in Management of Acute Pediatric Bipolar Depression: A Systematic Review and Meta-analysis

Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Methods: We conducted a systematic review for randomized clinical trials (RCTs) for PBD in MEDLINE, Scopus, and EMBASE. Four (quetiapine: 2, lurasidone: 1, olanzapine-fluoxetine combination [OFC]: 1) out of 569 studies met the criteria for inclusion in meta-analysis. RevMan was used for statistical analysis, and the mean difference (MD) between mean children's depression rating scale-revised (CDRS-R) score was used to measure treatment difference between SGA and placebo. Results: Lurasidone displayed a significant reduction in depressive symptoms (MD -5.70, 95% confidence interval [CI] -8.67 to -2.73) in PBD, followed by OFC (MD -5.00, 95% CI -8.64 to -1.36) and quetiapine (MD -2.30, 95% CI -6.80 to 2.20; MD 1.00, 95% CI -9.88 to 11.88). The response was significantly higher for lurasidone (59.5% vs. 36.5%; p < 0.001) and OFC (78.2% vs. 59.2%, p = 0.003) compared with placebo. There was no statistically significant MD in treatment and response rates between quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.58 (95% CI -6.59 to -2.56) and overall effect was significant (p < 0.00001). Importantly, the p value for heterogeneity was 0.46, which indicated that there was no heterogeneity between outcomes of the studies. The number needed to treat (NNT) for lurasidone was 4.3, followed by OFC (NNT = 5.3) and quetiapine (NNT = 12.5; NNT = 25). Conclusion: Our findings showed lurasidone and OFC were more efficacious than placebo for acute depressive episodes in PBD. RCTs of treatments for PBD remain scarce pressing the need for more research.