Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression

Summary & key facts

This phase 3, double-blind trial tested whether continuing esketamine nasal spray plus an oral antidepressant could delay relapse in adults with treatment-resistant depression who had already improved after an initial esketamine course. Of 297 patients who entered the randomized phase, continuing esketamine reduced relapse compared with switching to placebo nasal spray: among 176 patients in remission, 26.7% relapsed on esketamine vs 45.3% on placebo (P = .003; NNT = 6); among 121 patients with response but not remission, 25.8% relapsed on esketamine vs 57.6% on placebo (P < .001; NNT = 4). The study reported hazard ratios showing a 51% lower risk of relapse in the remission group (HR 0.49;

Key facts:

• This was a phase 3, multicenter, double-blind, randomized withdrawal study registered as NCT02493868 and run from October 6, 2015, to February 15, 2018.
• A total of 705 adults were enrolled; 455 entered the optimization phase and received esketamine plus an oral antidepressant; 297 who met response or remission criteria entered the randomized maintenance phase.
• Among the 176 patients who achieved stable remission, 24 of 90 (26.7%) assigned to continue esketamine relapsed, compared with 39 of 86 (45.3%) assigned to switch to placebo nasal spray (log-rank P = .003; number needed to treat = 6).
• Among the 121 patients who achieved stable response without remission, 16 of 62 (25.8%) continuing esketamine relapsed, compared with 34 of 59 (57.6%) switching to placebo (log-rank P < .001; number needed to treat = 4).
• Risk of relapse was reduced by 51% in the remission group (hazard ratio 0.49; 95% CI, 0.29–0.84) and by 70% in the response group (hazard ratio 0.30; 95% CI, 0.16–0.55) for esketamine plus antidepressant versus antidepressant plus placebo s
• Common adverse events after randomization in esketamine-treated patients were transient dysgeusia, vertigo, dissociation, somnolence, and dizziness, each occurring in 20.4%–27.0% of esketamine patients and in fewer than 7% of patients on an
• The study included adults with prospectively confirmed treatment-resistant depression (mean age 46.3 years; 66.3% female in the randomized phase).
• The paper notes potential conflicts of interest: several authors were employees of the drug maker and many authors disclosed consulting or financial ties to pharmaceutical companies.

Abstract

ClinicalTrials.gov identifier: NCT02493868.

Topics

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Anesthesia Antidepressant Depression (economics) Economics Hippocampus Internal medicine Macroeconomics Medicine Nasal administration Nasal spray Pathology Pharmacology Placebo Randomized controlled trial Treatment-resistant depression