The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials

Background: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once -daily, 14 -day treatment course for adults with PPD in the US-on health -related quality of life, including functioning and well-being, as assessed using the 36 -item Short Form Health Survey V2 (SF -36). Methods: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF -36 domains were compared for zuranolone (30- and 50 -mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (>= 50 % reduction from baseline in 17 -item Hamilton Depression Rating Scale total score) and nonresponders were assessed. Results: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). Limitations: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p -values presented are nominal. Conclusions: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and wellbeing across all SF -36 domains. Benefits persisted after completion of treatment course at D42.