Esketamine Nasal Spray Efficacious in TRD Vs. Placebo

Esketamine (ESK) nasal spray monotherapy was found to be efficacious over placebo in adults with treatment-resistant depression, according to recent randomized, double-blind study results reported in a poster at Psych Congress 2024.  

Participants with major depressive disorder (MDD) with no psychotic features, a score of ≥34 on the 30-item Inventory of Depressive Symptomatology (IDS-C30), and nonresponse (≤25% improvement) to ≥2 oral antidepressant (OADs) were enrolled. Participants underwent a ≥2-week OAD-free period and were randomly assigned 2:1:1 to receive placebo or fixed-dose ESK (56/84mg) twice weekly for 4 weeks. Participants with Montgomery-Åsberg Depression Rating Scale (MADRS) scores ≥28 at screening and baseline and with ≤25% improvement from screening to baseline were included. Primary and key secondary endpoints were changes in MADRS total score from baseline to day 28 (D28) and D2 (~24 hours after first dose), respectively. 

A total of 378 patients were included with 86 receiving 56mg of esketamine, 95 participants receiving 84mg esketamine, and 197 receiving placebo.  Mean change from baseline in MADRS score at D28 with esketamine was superior to placebo (least-squares mean difference [SE]: 56mg: −5.1[1.42]; 84mg: −6.8[1.38]; P< 0.001). At D2, change from baseline in MADRS score for ESK (56mg: p=0.004; 84mg: P=0.006) was also superior to placebo.

The most common (≥10%) treatment-emergent adverse events for combined ESK groups were nausea, dissociation, dizziness, and headache. No new safety concerns were found.

Johnson & Johnson sponsored the poster.

Reference
Himedan J, et al. Esketamine nasal spray as monotherapy for treatment-resistant depression. Poster presented at Psych Congress; October 29 – November 2, 2024; Boston, Massachusetts.