A scoping review: ketamine or esketamine when used to assist psychotherapy or in combination with psychotherapy for the management of depression in adults
Jennifer Swainson, P. Grewal, S. Polard, C. Borle, Gilmar Gutierrez, Y. Zhang, Olga Winkler, Lisa Burback, Atul Khullar, Roger S McIntyre, Elisa Brietzke, C.N. Soares
npj Mental Health Research July 27, 2026 DOI: 10.1038/s44184-026-00226-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Scoping review Randomized Open-label Peer reviewed |
|---|---|
| Sample size | 47 |
| Population | Studies of ketamine or esketamine with psychotherapy for depression |
| Topics | Depression Esketamine Ketamine |
| Key findings | The review categorizes 47 studies into KAP and KCP models. KAP studies were limited by lack of RCTs and comparison groups, while three higher-quality studies suggested benefit from combining ketamine with cognitive behavioral therapy (KCP). More high-quality research with accurate reporting is needed. |
Abstract
This scoping review maps literature for use of ketamine or esketamine with psychotherapy for depression or depressive symptoms. Forty-seven studies were identified including 4/47 (9%) randomized controlled trials, 4/47 (9%) open label trials, 27/47 (57%) observational or retrospective studies, and 12/47 (26%) individual case reports. Studies were categorized as Ketamine/Esketamine Combined with Psychotherapy (KCP/ES-KCP), where an altered state is not necessary for psychotherapy, or Ketamine/Esketamine Assisted Psychotherapy (KAP/ES-KAP), where an altered state and/or integration of the experience is central to the psychotherapy. The 47 included 23/47(49%) KAP, 1/47 (2%) ES-KAP, 7/47 (15%) KCP, 3/47 (6%) ES-KCP, 8/47 (17%) dual KAP/KCP and 1/47 (2%) dual ES-KAP/ES-KCP. Four studies could not be categorized. Separation into these categories was useful to more clearly report current state of the literature. Though previous reviews have suggested KAP is of benefit for depression, KAP studies were limited by lack of RCTs, lack of comparison groups without psychotherapy, and a large number of individual case reports. To date, fewer studies, but higher quality data support a KCP model, with 3 studies suggesting benefit to combining ketamine with cognitive behavioral therapy (CBT). Further, high quality research including accurate reporting and description of psychotherapy model is required.
Comparable studies
Other narrative reviews on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |