Summary

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• This summary is based on the review of five systematic review(s)/meta-analysis(es). ^[1-5]
• Zuranolone demonstrated significant effectiveness in treating major depressive disorder (MDD) and postpartum depression (PPD), with notable improvements in depression rating scales such as the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Edinburgh Postnatal Depression Scale (EPDS). These improvements were particularly significant by day 15, with both 30 mg and 50 mg doses showing over 50% reductions in HAM-D scores compared to placebo.
• In comparative studies, zuranolone was more effective than selective serotonin reuptake inhibitors (SSRIS), showing a 7.43-point larger reduction in EPDS scores by day 45. Network meta-analyses revealed that estradiol and brexanolone were also highly effective, but zuranolone maintained a strong comparative position in reducing PPD symptoms.
• Population and subgroup analysis showed that zuranolone significantly improved outcomes in both PPD and MDD subgroups, with more pronounced changes in HAM-D and EPDS scores. These effects were observed across adults aged 18 to 75 years, demonstrating broad applicability across age groups in treating depressive symptoms.
• Zuranolone exhibited a higher incidence of treatment-emergent adverse events (TEAES) compared to placebo, with dizziness (relative risk (RR) 2.17) and somnolence (RR 2.43) being the most commonly reported events. These adverse events were generally mild and temporary.
• There were no significant differences in the overall incidence of serious adverse events (SAES) between zuranolone and placebo, and no notable differences in adverse event rates between subgroups, including PPD and MDD patients. The 30 mg dose group experienced fewer headaches compared to higher doses.
• The studies included adults aged 18 to 75 years with diagnoses of MDD, PPD, or insomnia. Significant improvements were observed in depression scales (e.g., HAM-D, EPDS) for both MDD and PPD subgroups, with better outcomes in PPD patients compared to SSRIs. No substantial differences in safety outcomes were noted across age groups or between MDD and PPD patients.