Esketamine for treatment-resistant depression: Comparing two maintenance schedules in an observational real-world study

Summary

For people with treatment-resistant depression, intranasal esketamine significantly reduced depressive symptoms during an initial four-week induction phase. After induction, two different maintenance schedules—one with a front-loaded pattern and one with a spaced interval-extension pattern—were compared. No significant differences in depressive symptom trajectories were observed between the two schedules over the maintenance period. By the end of maintenance, response rates were 35.3% on the clinician-rated scale and 26.0% on the self-report scale; remission rates were 31.4% and 38.0%, respectively. These results suggest that maintenance dosing intervals may be scheduled flexibly without loss of efficacy, though the retrospective, observational design and small sample size warrant caution.

Study at a glance

Abstract

Abstract Background : Treatment-resistant depression (TRD) is associated with substantial clinical and socioeconomic burden. Intranasal esketamine has shown efficacy for TRD in clinical trials and real-world studies. However, evidence on optimal maintenance scheduling is limited. We therefore investigated whether two maintenance schedules differing in their inter-dose intervals were associated with different depressive symptom trajectories. Methods : We retrospectively analysed 65 patients with TRD undergoing intranasal esketamine treatment as part of routine outpatient care between January 2021 and April 2025. Treatment consisted of an induction phase of eight sessions over four weeks, followed by either a front-loaded or a spaced interval-extension maintenance schedule. Depressive symptoms were assessed using clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory-II (BDI). Results : Depressive symptoms decreased significantly during the induction phase on both MADRS (d = 1.03) and BDI (d = .72). During the maintenance phase, contrasts showed no significant differences between the two maintenance schedules on either outcome. By the end of maintenance, response rates were 35.3% on the MADRS and 26.0% on the BDI, while remission rates were 31.4% and 38.0%, respectively. Conclusion: Esketamine was associated with significant reductions in depressive symptoms during the induction phase. No significant differences in depressive symptom trajectories were observed between the two maintenance schedules. This finding suggests that maintenance dosing intervals may be scheduled flexibly without loss of efficacy. Given the retrospective, observational design and the small sample size, results should be interpreted with considerable caution. Randomised trials with larger sample sizes are needed to confirm our findings.