Background
In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high.
The Efficacy and Safety of Esketamine Nasal Spray Compared to Extended-Release Quetiapine Augmentation Therapy , Both in Combination With Continued Treatment With a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin Reuptake Inhibitor -norepinephrine (SNRI), in patients with treatment-resistant disease of depression are unknown.
Methods
In an open-label, single-blind (with evaluators unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible dosing (according to with summary of product characteristics) of esketamine nasal spray (esketamine group) or quetiapine extended-release (quetiapine group), both in combination with an SSRI or an SNRI.
The primary endpoint was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicate more severe depression).
The key secondary endpoint was no relapse until week 32 after remission at week 8. All patients were included in the analysis; Patients who discontinued trial treatment were considered to have had an unfavorable outcome (ie, they were grouped with patients who did not have remission or who had a relapse).
Analyzes of primary and key secondary endpoints were adjusted for age and number of treatment failures.
Results
In total, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] versus 60 of 340 patients [17.6%]; P = 0.003) and had no relapse until week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]).
During 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with treatment response, and the change in MADRS score from baseline favored esketamine nasal spray.
Adverse events were consistent with established safety profiles of the trial treatments.
Conclusions In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. |
(Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321. opens in new tab.)
