Zuranolone for the Treatment of Postpartum Depression.

OBJECTIVE: Postpartum depression (PPD) is a common perinatal complication with adverse maternal and infant outcomes. This study investigated the efficacy and safety of zuranolone, a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid, as an oral, once-daily, 14-day treatment course for patients with severe PPD. METHODS: In this double-blind phase 3 trial, women with severe PPD were randomized in a 1:1 ratio to receive zuranolone 50 mg/day or placebo for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15; key secondary endpoints were change from baseline in HAM-D score at days 3, 28, and 45 and change from baseline in Clinical Global Impressions severity (CGI-S) score at day 15. Adverse events were monitored. RESULTS: Among 196 patients randomized (zuranolone, N=98; placebo, N=98), 170 (86.7%) completed the 45-day study. Treatment with zuranolone compared with placebo resulted in statistically significant improvement in depressive symptoms at day 15 (least squares mean [LSM] change from baseline in HAM-D score, -15.6 vs. -11.6; LSM difference, -4.0, 95% CI=-6.3, -1.7); significant improvement in depressive symptoms was also reported at days 3, 28, and 45. CGI-S score at day 15 significantly improved with zuranolone compared with placebo. The most common adverse events (≥10%) with zuranolone were somnolence, dizziness, and sedation. No loss of consciousness, withdrawal symptoms, or increased suicidal ideation or behavior were observed. CONCLUSIONS: In this trial, zuranolone demonstrated significant improvements in depressive symptoms and was generally well tolerated, supporting the potential of zuranolone as a novel, rapid-acting oral treatment for PPD.

Digital health technologies and major depressive disorder.

There is an urgent need to improve the clinical management of major depressive disorder (MDD), which has become increasingly prevalent over the past two decades. Several gaps and challenges in the awareness, detection, treatment, and monitoring of MDD remain to be addressed. Digital health technologies have demonstrated utility in relation to various health conditions, including MDD. Factors related to the COVID-19 pandemic have accelerated the development of telemedicine, mobile medical apps, and virtual reality apps and have continued to introduce new possibilities across mental health care. Growing access to and acceptance of digital health technologies present opportunities to expand the scope of care and to close gaps in the management of MDD. Digital health technology is rapidly evolving the options for nonclinical support and clinical care for patients with MDD. Iterative efforts to validate and optimize such digital health technologies, including digital therapeutics and digital biomarkers, continue to improve access to and quality of personalized detection, treatment, and monitoring of MDD. The aim of this review is to highlight the existing gaps and challenges in depression management and discuss the current and future landscape of digital health technology as it applies to the challenges faced by patients with MDD and their healthcare providers.