Exploring the durability of esketamine and ketamine's antidepressant effects in the maintenance phase of treatment: A systematic review
Shreya Vasudeva, Diana Orsini, Gabrielle F. M. Lovell, Sara Di Luch, Gia Han Le, Sabrina Wong, Roger S McIntyre, Joshua Daniel Rosenblat
Psychiatry Research October 29, 2026 DOI: 10.1016/j.psychres.2026.117556 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Open-label Case report Peer reviewed |
|---|---|
| Population | Individuals with mood disorders receiving repeated ketamine or esketamine during maintenance treatment |
| Interventions | Ketamine Esketamine |
| Duration | More than 1 month of treatment (inclusion criterion); more than 8 treatments (inclusion criterion) |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine and esketamine were associated with sustained clinical improvement during ongoing maintenance treatment, though outcomes varied by study design. Randomized trials showed reduced relapse rates with continued treatment, while relapse was common after discontinuation; observational studies and case series reported mixed durability, with both sustained improvement and attenuation of benefit over time. |
Abstract
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.
Comparable studies
Other systematic reviews and meta-analyses on esketamine, most cited first.
Citations in the library
Cites 39
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
and 34 more in the library