Evaluating zuranolone: Discrepancies and insights from multiple systematic reviews and meta-analyses on major depression and postpartum depression treatment

• Zuranolone demonstrates significant improvement in depressive symptoms with effects noticeable by day 15 in MDD and PPD. • Different systematic reviews exhibit varied results due to methodological and population differences. • Increased adverse events like dizziness and somnolence, especially at higher doses. • Systematic reviews highlight variations in efficacy across different cultural contexts. Zuranolone, a novel neuroactive steroid and positive allosteric modulator of γ-aminobutyric acid type A (GABA A ) receptors, has been explored for its potential in treating major depressive disorder (MDD) and postpartum depression (PPD). This review compiles findings from multiple systematic reviews and meta-analyses, emphasizing its rapid action and efficacy in alleviating depressive symptoms. Significant improvement is consistently observed by day 15 of treatment, positioning zuranolone as a promising option for rapid relief in depressive episodes. However, variability in research outcomes and methodology across different studies highlights the complexity of evaluating new treatments. Safety concerns, particularly at higher doses, and the increased incidence of side effects such as dizziness and somnolence, call for cautious dose management and close monitoring. Cultural and regional differences also influence treatment efficacy, suggesting the need for culturally sensitive clinical practices. This review underscores the therapeutic potential of zuranolone while also noting the necessity for further research to address safety concerns and optimize treatment protocols.