Characterizing the efficacy of zuranolone across patient subgroups and symptom domains in Japanese patients with major depressive disorder: a pooled analysis of two placebo-controlled trials
- 1Department of Neuropsychiatry, Kansai Medical University
- 2Drug Development and Regulatory Science Division, Shionogi & Co., Ltd.
- 3Department of Psychiatry, Fujita Health University School of Medicine
Abstract
Aim: Zuranolone has been reported to reduce the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score as early as Day 3 in Japanese patients with major depressive disorder (MDD), with the reduction in the HAM-D17 total score being maintained after the treatment period. This post hoc pooled analysis aimed to evaluate the treatment effects of zuranolone across baseline characteristics and to characterize how changes in specific symptom domains—core, anxiety, and insomnia—were associated with the early reduction in the HAM-D17 total score and its subsequent trajectory, using pooled data from two randomized, double-blind, placebo-controlled Phase 2 and Phase 3 trials.
Methods: Data from the Phase 2 and Phase 3 trials were combined for efficacy and safety analyses. Participants were randomly assigned to receive either oral zuranolone or placebo daily for 14 days and followed up for 6 weeks. The endpoints included the change from baseline in the HAM-D17 total score, response and remission rates, subgroup analyses, and subscale scores (core, anxiety, and insomnia) and their relative contributions to the between-group difference (zuranolone vs. placebo) in the HAM-D17 total score.
Results: The pooled full-analysis set included 284 and 278 participants in the zuranolone and placebo groups, respectively. The treatment effects were consistent across subgroups defined by baseline severity, sex, episode recurrence, and other characteristics. The HAM-D17 subscale analyses indicated reductions in scores across the core, anxiety, and insomnia subscales during the treatment period, with reductions in the insomnia subscale score accounting for the largest between-group difference. During the follow-up period, the reduction in the insomnia subscale score tended to decrease, whereas reductions in the core and anxiety subscale scores were relatively maintained.
Conclusion: Zuranolone showed consistent treatment effects regardless of baseline characteristics. During the treatment period, early improvement in depressive symptoms was accompanied by improvements across all symptom domains, and improvements in core and anxiety symptom domains appeared to be relatively maintained during the follow-up period. These symptom domain-specific temporal profiles could suggest patterns of antidepressant response and symptom change following treatment with zuranolone. Given the exploratory nature of this analysis, these findings should be interpreted descriptively and require confirmation in future hypothesis-driven studies.
Related
- Adjunctive Psychobiotic Lactiplantibacillus plantarum PS128 Therapy and Escitalopram in Major Depressive Disorder: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial
- Questionable mediated effect of self-efficacy on depressive symptoms among college students: A reassessment of Desai and Lueke (2026)
- Efficacy and safety of non-hormonal pharmacotherapies for depressive and anxiety symptoms during the menopausal transition and postmenopause: a systematic review.
- Functional electrical stimulation for major depressive disorder: Protocol for a pilot randomized controlled trial
- A randomized, controlled experimental medicine study of the novel Kv7 channel opener azetukalner in individuals with major depressive disorder and anhedonia
BibTeX
@article{kato2026characterizing,
title = {{Characterizing the efficacy of zuranolone across patient subgroups and symptom domains in Japanese patients with major depressive disorder: a pooled analysis of two placebo-controlled trials}},
author = {Masaki Kato and Takamichi Baba and Takuhiro Sonoyama and Nakao Iwata},
journal = {Frontiers in Psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1891881},
url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1891881/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Characterizing the efficacy of zuranolone across patient subgroups and symptom domains in Japanese patients with major depressive disorder: a pooled analysis of two placebo-controlled trials
AU - Masaki Kato
AU - Takamichi Baba
AU - Takuhiro Sonoyama
AU - Nakao Iwata
PY - 2026
DA - 2026/10/22
JO - Frontiers in Psychiatry
DO - 10.3389/fpsyt.2026.1891881
UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1891881/full
AB - Aim: Zuranolone has been reported to reduce the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score as early as Day 3 in Japanese patients with major depressive disorder (MDD), with the reduction in the HAM-D17 total score being maintained after the treatment period. This post hoc pooled analysis aimed to evaluate the treatment effects of zuranolone across baseline characteristics and to characterize how changes in specific symptom domains—core, anxiety, and insomnia—were associated with the early reduction in the HAM-D17 total score and its subsequent trajectory, using pooled data from two randomized, double-blind, placebo-controlled Phase 2 and Phase 3 trials. Methods: Data from the Phase 2 and Phase 3 trials were combined for efficacy and safety analyses. Participants were randomly assigned to receive either oral zuranolone or placebo daily for 14 days and followed up for 6 weeks. The endpoints included the change from baseline in the HAM-D17 total score, response and remission rates, subgroup analyses, and subscale scores (core, anxiety, and insomnia) and their relative contributions to the between-group difference (zuranolone vs. placebo) in the HAM-D17 total score. Results: The pooled full-analysis set included 284 and 278 participants in the zuranolone and placebo groups, respectively. The treatment effects were consistent across subgroups defined by baseline severity, sex, episode recurrence, and other characteristics. The HAM-D17 subscale analyses indicated reductions in scores across the core, anxiety, and insomnia subscales during the treatment period, with reductions in the insomnia subscale score accounting for the largest between-group difference. During the follow-up period, the reduction in the insomnia subscale score tended to decrease, whereas reductions in the core and anxiety subscale scores were relatively maintained. Conclusion: Zuranolone showed consistent treatment effects regardless of baseline characteristics. During the treatment period, early improvement in depressive symptoms was accompanied by improvements across all symptom domains, and improvements in core and anxiety symptom domains appeared to be relatively maintained during the follow-up period. These symptom domain-specific temporal profiles could suggest patterns of antidepressant response and symptom change following treatment with zuranolone. Given the exploratory nature of this analysis, these findings should be interpreted descriptively and require confirmation in future hypothesis-driven studies.
SN - 1664-0640
ER -