Exploring the durability of esketamine and ketamine's antidepressant effects in the maintenance phase of treatment: A systematic review
- Journal
- Psychiatry research (Q1)
- Published
- 29 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Shreya Vasudeva, Diana K Orsini, Gabrielle F M Lovell, Sara Di Luch, Gia Han Le, Sabrina Wong, et al.
- PMID
- 42981896
- DOI
- 10.1016/j.psychres.2026.117556
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (paper of the day, 6 November 2026): Reviews maintenance ketamine and esketamine for treatment-resistant mood disorders
Abstract
Ketamine has shown rapid antidepressant effects in treatment-resistant mood disorders; however, the durability of these benefits during maintenance treatment remains unclear. This systematic review evaluated outcomes associated with repeated ketamine and esketamine administration during the maintenance phase of treatment. A systematic search of PubMed, Ovid, and Scopus was conducted from database inception through March 2026. Studies involving more than 8 treatments or more than 1 month of treatment in individuals with mood disorders were included. Eligible designs consisted of randomized controlled trials, open-label studies, observational cohorts, and case series. A total of 43 studies met inclusion criteria, including randomized controlled trials and extension studies (n = 8), open-label studies (n = 4), observational studies (n = 24), and case series (n = 7). Overall, ketamine and esketamine were associated with sustained clinical improvement during ongoing treatment, although outcomes varied across study designs. Randomized trials demonstrated reduced relapse rates with continued treatment, while relapse was common following discontinuation of treatment. Observational studies showed heterogeneous outcomes, with evidence of both sustained improvement and attenuation of benefit over time. Case series reported mixed durability. These findings suggest that continued treatment may be important for preserving therapeutic benefit, although long-term outcomes are not uniform across individuals. Further research is needed to optimize maintenance strategies, identify predictors of sustained response, and clarify the long-term efficacy and safety of ketamine-based therapies for mood disorders.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.