Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials
Pooled analyses of three short-term randomised controlled trials found that esketamine nasal spray plus a newly initiated oral antidepressant produced greater reductions in MADRS total score than antidepressant plus placebo in both women and men with treatment‑resistant depression, with no significant sex effect or treatment-by-sex interaction. Overall safety was similar between sexes, although nausea, dissociation, dizziness and vertigo were reported more frequently in women.
Authors
- Carla Maria Canuso
- Ella Daly
Published
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)).
Research Summary of 'Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials'
Introduction
Women have about a twofold greater lifetime risk of major depressive disorder than men and frequently differ from men in clinical presentation, comorbidities and treatment course. Previous large observational studies have reported earlier age at onset, greater episode severity and longer episode duration in women, and sex differences have been reported for response and adverse effects with conventional antidepressants. Findings have been mixed for newer treatments: some studies report no sex difference in rapid-acting ketamine response, while others show variable effects related to menopausal status or hormone therapy with biogenic-amine antidepressants. Jones and colleagues conducted a post hoc analysis of three short-term, phase 3 randomized controlled TRANSFORM trials of esketamine nasal spray plus a newly initiated oral antidepressant in patients with treatment-resistant depression (TRD). The analysis aimed primarily to determine whether efficacy (change in depressive symptoms, response and remission rates, and comorbid anxiety) and overall safety differ between women and men. Secondarily, among women the investigators examined whether outcomes varied by menopausal status or by use of systemic hormonal therapy, and whether clinical factors differentiated responders from non-responders to inform clinical decision-making for women with TRD.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Jones, R. R., Freeman, M. P., Kornstein, S. G., Cooper, K., Daly, E. J., Canuso, C. M., & Nicholson, S. (2022). Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials. Archives of Women's Mental Health, 25(2), 313-326. https://doi.org/10.1007/s00737-021-01185-6
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References (1)
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Chen, X., Hou, X., Bai, D. et al. · American Journal of Psychiatry (2019)
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