The New England Journal of MedicineEsketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

Study reveals esketamine nasal spray, in combination with SSRI or SNRI, outperforms extended-release quetiapine in patients with treatment-resistant depression.

A recent phase 3b trial has shed light on the potential of esketamine nasal spray as a viable treatment option for patients suffering from treatment-resistant depression. The study compared the efficacy and safety of esketamine nasal spray with extended-release quetiapine augmentation therapy, both used in conjunction with a selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI).

HCN Medical Memo
This study underscores the potential of esketamine nasal spray as an effective treatment for patients with treatment-resistant depression. Healthcare professionals should consider this option when treating patients who have not responded to two or more consecutive treatments during their current depressive episode.

Study Design

• The study was an open-label, single-blind, multicenter, phase 3b, randomized, active-controlled trial.
• Patients were assigned in a 1:1 ratio to receive flexible doses of esketamine nasal spray or extended-release quetiapine, both in combination with an SSRI or SNRI.
• The primary end point was remission at week 8, defined as a score of 10 or less on the Montgomery–Åsberg Depression Rating Scale (MADRS).
• The key secondary end point was no relapse through week 32 after remission at week 8.

Esketamine nasal spray is a potent variant of the drug ketamine, which has been used for 50 years in medical settings as an FDA-approved anesthetic. Unlike traditional antidepressants, esketamine works via the glutaminergic system rather than the monoaminergic system to achieve its therapeutic effect.

Key Findings

• More patients in the esketamine group had remission at week 8 and had no relapse through week 32 after remission at week 8.
• 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.

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