Key Takeaways
Extended Takeaways
- Concurrent remission of depression and anxiety emerged rapidly with zuranolone: using HDRS-17 total score ≤ 7 plus HARS total score ≤ 7, rates were 18.9% vs 2.7% at day 3, 40.5% vs 19.2% at day 15, and 52.1% vs 23.2% at day 45.
- Sustained dual remission favored zuranolone over placebo, with odds ratio [95% CI] of 6.2 [2.2 to 17.4] for combined HDRS-17/HARS remission and 3.7 [1.5 to 8.9] for combined MADRS/HARS remission at both days 15 and 45.
- Anxiety-specific improvement was detectable by day 3 on the HDRS-17 Anxiety/Somatization subscale, with LS mean [SE; 95% CI] change of −3.8 [0.3; −4.5 to −3.2] versus −2.7 [0.3; −3.3 to −2.0] (P = .007), and the between-group advantage persisted to day 45.
- At day 15, response rates on anxiety measures were consistently higher with zuranolone, including HARS response of 71.6% vs 49.3% and HDRS-17 A/S response of 68.9% vs 46.6%, suggesting benefit beyond depressive symptom reduction alone.
- Patient-perceived recovery extended to functioning: by day 45, zuranolone improved SF-36v2 Social Functioning, Mental Health, Physical Functioning, Role Physical, Bodily Pain, and the Mental Component Summary score versus placebo, and Physical Functioning, Bodily Pain, General Health, and the Physical Component Summary reached US population normative levels.
- The indirect benefit-risk profile was clinically favorable in this trial, with NNT estimates of 5 [3 to 13] for HDRS-17 response and 5 [3 to 17] for remission at day 15, while NNH estimates were ≥ 10 for incidence of TEAEs and discontinuation due to an AE.
