Administered with a selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI), esketamine nasal spray produced greater remission at week 8 compared with extended-release quetiapine plus an SSRI or SNRI, a study shows. “Existing guidelines for the treatment of patients with treatment-resistant depression lack uniformity; collectively, these data provide support for the use of esketamine nasal spray in treatment-resistant depression and may be of value for informing future guidelines,” the authors write.
The phase 3b multicenter trial used an open-label, single-blind, randomized, active-controlled design. Participants received flexible doses of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. Based on a primary endpoint of remission (a score of 10 or less on the Montgomery–Åsberg Depression Rating Scale [MADRS] at week 8), the study showed the following: “Overall, 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%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments.”
Editorial: “Esketamine nasal spray will not be the only glutamate antagonist to find its way into clinical practice,” writes an editorialist. “A recent meta-analysis suggested that intravenous racemic ketamine may be more efficacious than esketamine, and two large head-to-head trials support the use of intravenous racemic ketamine later in the treatment pathway as an option for people who would otherwise need electroconvulsive therapy. Nevertheless, the ESCAPE-TRD trial supports the radical and disruptive idea that esketamine nasal spray has a place early in the sequence of antidepressant treatment. It seems to help prevent depression from consolidating its grip.”