Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response: A Pooled Post Hoc Analysis of the TRANSFORM Studies
This pooled analysis of two phase III studies (n=518, TRANSFORM) finds that for those who didn’t respond, continued treatment may still be beneficial. This was both true for the esketamine group and the group that received a placebo.
Authors
- Scott Wilkinson
- Ibrahim Turkoz
- Ella Daly
Published
Abstract
Objective
To evaluate response to esketamine nasal spray plus an oral antidepressant (ESK + AD) at day 28 in patients with major depressive disorder (DSM-5) and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment.
Methods
The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale total score at day 2 or days 2 and 8. Response rates at day 28 were determined among those not meeting early response criteria.
Results
518 patients in the analysis had day 28 observations (ESK + AD, n = 310; AD + PBO, n = 208). A greater percentage of patients treated with ESK + AD versus AD + PBO met response criteria beginning at day 2 (17.3% [55/318] vs 9.4% [19/203]) and at all subsequent timepoints, including day 28 (58.7% [182/310] vs 45.2% [94/208]). In day 2 nonresponders, 54.9% vs 44.3% (ESK + AD vs AD + PBO, respectively) achieved response at day 28 (P < .01). Similarly, among day 2 and 8 nonresponders, 52.1% vs 42.4% achieved response by day 28 (P = .01). In nonresponders at day 2 and at days 2 and 8, the odds ratio for a response at day 28 was 1.61 (95% CI, 1.09-2.40) with ESK + AD versus 1.56 (95% CI, 1.04-2.35) with AD + PBO.
Conclusions
Patients with TRD without a demonstrated response within the first week of treatment may still derive benefit from a full 4-week induction course of esketamine nasal spray.
Research Summary of 'Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response: A Pooled Post Hoc Analysis of the TRANSFORM Studies'
Introduction
Major depressive disorder (MDD) causes substantial morbidity and disability, and a sizeable proportion of patients do not achieve an adequate response after multiple oral antidepressant trials. The term treatment-resistant depression (TRD) is used for patients who fail to respond to ≥ 2 antidepressants in the current major depressive episode, and for many patients the cumulative time spent on ineffective treatments is substantial. Rapid-acting therapies such as ketamine analogues have raised expectations for early improvement, yet individual trajectories vary and lack of an early response does not necessarily predict ultimate nonresponse. Turkoz and colleagues set out to examine whether adults with TRD who do not show an early response to treatment with esketamine nasal spray plus a newly started oral antidepressant (ESK + AD) might nevertheless achieve a clinically meaningful response by the end of a standard 4-week induction phase. Using pooled data from two Phase III, double-blind, active-controlled TRANSFORM studies, the analysis specifically estimated day 28 response rates among patients who failed to meet predefined early-response criteria at day 2 or at days 2 and 8.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Turkoz, I., Daly, E., Singh, J., Lin, X., Tymofyeyev, Y., Williamson, D., Salvadore, G., Nash, A. I., Macaluso, M., Wilkinson, S. T., & Nelson, J. C. (2021). Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response: A Pooled Post Hoc Analysis of the TRANSFORM Studies. The Journal of Clinical Psychiatry, 82(4). https://doi.org/10.4088/jcp.20m13800
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