This study evaluated the efficacy and safety/tolerability of quetiapine extended-release 300 mg/day (QUEXR300), quetiapine immediate-release 600 mg/day (QUEIR600), and quetiapine immediate-release 300 mg/day (QUEIR300) formulations for treating bipolar depression. A random-effect network meta-analysis of 8-week, double-blind, randomized placebo-controlled trials was used to determine the most optimal agent for intervention. Remission rate was set as the primary outcome. Secondary outcomes were response rate, improvement in the Montgomery–Åsberg Depression Rating Scale score, discontinuation rate, and the incidence of individual adverse events. Seven eligible studies including 3267 participants were included in the meta-analysis. The QUEIR600, QUEIR300, and QUEXR300 groups were superior to the placebo group in every efficacy outcome; however, there were no significant differences in the efficacy outcomes among the treatment groups. All treatment groups exhibited higher incidences of extrapyramidal symptoms, dry mouth, somnolence, constipation, and increase in body weight than the placebo group. The QUEIR600 and QUEIR300 groups had higher incidences of dizziness than the placebo group. The QUEIR600 group had a higher discontinuation rate due to adverse events than the placebo group, and the QUEIR300 group had higher blood HbA1c levels than the placebo group. The QUEIR600 and QUEXR300 groups had higher incidences of ≥7% weight gain than the placebo group. The QUEXR300 group had a higher incidence of fatigue than the QURIR300 and placebo groups. In conclusion, there were no significant differences in the efficacies of QUEIR600, QUEIR300, and QUEXR300 in treating bipolar depression; moreover, tolerance to QUEIR600 might be worse than the other treatments.
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