The following is a summary of “Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression,” published in the October 2023 issue of Psychiatry by Reif et al.

Treatment-resistant depression is a difficult-to-treat condition with low remission and high relapse rates. Esketamine nasal spray is a new treatment being investigated for its efficacy and safety in combination with selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI) antidepressants.

Researchers started a retrospective study to compare the efficacy and safety of esketamine nasal spray and extended-release quetiapine for treating treatment-resistant depression in patients already taking SSRI or SNRI antidepressants.

They conducted a multicenter, phase 3b, randomized trial in which patients were assigned in a 1:1 ratio to receive flexible doses of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both with an SSRI or SNRI. At the same time, raters remained unaware of group assignments. The main goal was achieving remission (defined as Montgomery–Åsberg Depression Rating Scale (MADRS) score ≤ 10) at week 8, and the key secondary goal was avoiding relapse up to week 32 after achieving remission. All patients, even those who stopped treatment, were analyzed, with adjustments made for age and treatment failures.

The results showed 336 patients in the esketamine group and 340 in the quetiapine group. A higher percentage of patients in the esketamine group achieved remission at week 8 (27.1% of 336 patients) compared to the quetiapine group (17.6% of 340 patients; P=0.003), and they also had fewer relapses through week 32 after week 8 remission (21.7% of 336 patients vs. 14.1% of 340 patients). Esketamine nasal spray was more effective than quetiapine in achieving remission, treatment response, and reducing depressive symptoms over 32 weeks. Adverse events were consistent with the integrated safety profiles of the trial treatments.

They concluded that esketamine nasal spray was more effective than quetiapine in remission in patients with treatment-resistant depression at week 8.

Source: nejm.org/doi/full/10.1056/NEJMoa2304145