Esketamine for treatment-resistant depression: Comparing two maintenance schedules in an observational real-world study
Samuel Westenhöfer, Yamina Ehrt, Barbora Provaznikova, Susanne Prinz, Marie Spies, Liliia Akhmetova, Niluja Nadesalingam, Eliane Strickler, Rainer Krähenmann, Erich Seifritz, Sebastian Olbrich, Johannes Jungwirth
Research Square July 9, 2026 preprint DOI: 10.21203/rs.3.rs-10250654/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective observational cohort Randomized |
|---|---|
| Sample size | 65 |
| Population | Patients with treatment-resistant depression undergoing intranasal esketamine treatment in routine outpatient care |
| Intervention | Intranasal esketamine |
| Duration | Induction phase of eight sessions over four weeks, followed by maintenance phase with variable inter-dose intervals |
| Topics | Depression Esketamine |
| Key findings | No significant differences in depressive symptom trajectories were observed between a front-loaded and a spaced interval-extension maintenance schedule for intranasal esketamine in treatment-resistant depression. |
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.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cites 23
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance The World Journal of Biological Psychiatry November 3, 2020
and 18 more in the library