Head-to-head data show esketamine (Spravato) pulls ahead — and stays ahead
STUDY: Reif A et al, N Engl J Med 2023;389:1298–309, PMID: 36322843
STUDY TYPE: Randomized, active-controlled trial
FUNDING: Janssen (Esketamine maker)
Background
When two antidepressants have failed, the odds of remission drop sharply. Quetiapine augmentation is a standard next move — but esketamine nasal spray (Spravato) has been waiting in the wings. This trial puts them head-to-head.
The Study
676 adults with treatment-resistant depression were randomized to esketamine nasal spray plus an SSRI or SNRI versus extended-release quetiapine plus an SSRI or SNRI for 32 weeks. The primary endpoint was remission at week 8, defined as a score of 10 or below on the Depression scale (MADRS). The key secondary endpoint was staying in remission through week 32.
Remission at week 8 favored esketamine (27% vs. 18%; odds ratio 1.74). The advantage held at week 32, with nearly half of esketamine patients in remission versus a third on quetiapine. Patients on esketamine were also 1.55 times as likely to stay relapse-free through week 32.
Adverse events were more common with esketamine (92% vs. 78%), but most were mild, transient, and occurred on dosing days. Discontinuation due to side effects was actually lower with esketamine (4% vs. 11%).
Limitations: Open-label design: patients knew which treatment they were getting, which could influence both dropout and perceived response. Funded by the winner (esketamine).
Practice Implications
- Esketamine consistently outperformed quetiapine at every time point, though the open-label design is a serious limitation
- Each med has serious – and very different – risks
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- When would you choose esketamine vs. quetiapine?
