Key Takeaways

From the Authors As published in the article
  1. This study provides the first evidence of the long-term safety of 14-day treatment course(s) with zuranolone. The side effects of zuranolone in this study were consistent with those observed in previous clinical studies and were not notably different among patients who later relapsed and received repeat treatment courses, suggesting that the 14-day treatment course of zuranolone can potentially be repeated, if needed.
  2. Most patients achieved treatment response following a 14-day treatment course with zuranolone. Importantly, for patients who responded to their first treatment, the time to first repeat treatment was over 4 months in both dose groups, and they were likely to respond again if they later relapsed and needed additional treatment course(s).
Extended Takeaways
  1. Tolerability appeared dose sensitive: TEAEs leading to dose reduction occurred in 6.1% (44/725) of the 30-mg Cohort versus 18.6% (37/199) of the 50-mg Cohort, and TEAEs leading to study withdrawal occurred in 4.4% (32/725) versus 8.0% (16/199).
  2. Among initial Day 15 responders who stayed in follow-up, many did not require frequent retreatment over 1 year: 68.5% (335/489) in the 30-mg Cohort and 79.5% (116/146) in the 50-mg Cohort received only 1 or 2 total treatment courses.
  3. Symptom improvement after the first 14-day course was rapid and durable in those remaining on study, with mean (SD) HAMD-17 change from baseline of −15.2 (7.1) and −16.0 (6.0) at Day 15, and −12.2 (9.1) and −14.0 (7.2) still present at Day 70 in the 30-mg and 50-mg Cohorts, respectively.
  4. Repeat-course candidacy was operationalized with patient self-monitoring before clinician confirmation: a PHQ-9 score ≥ 10 triggered an in-clinic HAMD-17, and retreatment required HAMD-17 total score ≥ 20 with at least 56 days since the last dose.
  5. Retreatment can recapture benefit for many initial responders, particularly in the 30-mg Cohort: HAMD-17 response at Day 15 after the second course was 64.3% (171/266), and remained 63.6% (96/151), 66.7% (62/93), and 71.8% (28/39) across treatment cycles 3, 4, and 5.
  6. At study exit, most patients still in the full analysis set had no more than mild depressive severity despite whether they completed the year or withdrew early; by CGI-S, minimal/mild symptoms were seen in 84.9% (264/311) and 71.3% (127/178) of the 30-mg Cohort and 88.4% (84/95) and 74.5% (38/51) of the 50-mg Cohort.
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