Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials.
Robyn R Jones, Marlene P. Freeman, Susan G Kornstein, Kimberly Cooper, Ella Daly, Carla M. Canuso, Susan Nicholson
Archives of women's mental health April 2022 DOI: 10.1007/s00737-021-01185-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of three randomized controlled trials Peer reviewed |
|---|---|
| Sample size | 702 |
| Population | Adults with treatment-resistant depression, including those aged 18-64 (TRANSFORM-1/2) and 65 years or older (TRANSFORM-3) |
| Interventions | Esketamine nasal spray oral antidepressant |
| Duration | 4-week study with assessment at day 28 |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS) |
| Topics | Depression Esketamine |
| Keywords | Sex |
| Registration | NCT02417064 NCT02418585 NCT02422186 |
| Key findings | Esketamine nasal spray plus a new oral antidepressant reduced MADRS total scores more than antidepressant plus placebo in both women and men, with no significant sex effect or treatment-by-sex interaction (p > 0.35). The authors report that efficacy and overall safety were similar between sexes, though nausea, dissociation, dizziness, and vertigo were more common in women. |
Abstract
The objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18-64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women-esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men-esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women-esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men-esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.