Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review.
Jolien K E Veraart, Nina Schimmers, Joost J. Breeksema, Carolina Seybert, Jeanine Kamphuis, L F T Huber, A Rota, Daniël T Coerts, Albino J Oliveira-Maia, Robert A Schoevers
Clinical Psychology Review February 2, 2026 DOI: 10.1016/j.cpr.2026.102706 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Intervention | Ketamine-assisted psychotherapy |
| Topics | Esketamine Ketamine Psychedelic-assisted therapy |
| Keywords | Ketamine-assisted psychotherapy Psychiatric disorders Systematic review |
| Citations | 4 |
| Key findings | The limited evidence from randomized controlled trials does not support added benefit or synergistic effects from combining psychotherapy with ketamine in psychiatric disorders. |
Abstract
Ketamine-assisted psychotherapy (KAP) is considered a promising treatment strategy in psychiatric disorders, combining psychotherapeutic interventions with the rapid-acting pharmacological effects of ketamine towards enhancing outcomes. Although KAP has been practiced for many years across different diagnoses, evidence regarding optimal treatment methods and working mechanisms remains limited and has only partly been synthesized. This systematic review provides a historical overview of studies published up to 2025, that combined ketamine and psychotherapy for the treatment of mental disorders. Psychotherapeutic approaches were categorized into their overarching psychological paradigms: psychoanalytic and psychodynamic, behavioral, humanistic, cognitive-behavioral, integrative/holistic, and other therapeutic frameworks. 64 articles, reporting on 72 studies, were included in this review, of which only 11 were randomized controlled trials (RCTs), highlighting the limited representation of RCTs in the overall body of evidence. Diverse therapeutic approaches were found, most were classified into the 'other' category (n = 24). Results suggest transdiagnostic effectiveness for indications including major depressive disorder, posttraumatic stress disorder, obsessive-compulsive disorder, substance use disorders and eating disorders. KAP, compared to only psychotherapy, was observed to enhance treatment engagement, symptom reduction, and duration of treatment response. Only two studies randomized psychotherapy in the context of ketamine treatment, neither of which reported added effects for psychotherapy. One of those studies also randomized ketamine and did not find a significant interaction effect. This limited evidence does not support added benefit from psychotherapy nor evidence of synergy. Methodological heterogeneity and the limited number of trials that used a psychotherapy control group, restrict definitive conclusions. Clinical effects are generally reported to be quite positive across psychiatric indications, however, there is a clear need for well-controlled trials to test for potential additive or synergistic effects of the combined use of ketamine and psychotherapy and to identify optimal therapeutic protocols.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 5
- Esketamine and Acceptance and Commitment Therapy (ACT) for Treatment-Resistant Depression: An Intervention-Development Framework and Treatment Manual Psychedelics October 1, 2026
- Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy Journal of Affective Disorders August 10, 2026
- Navigating ‘k-land’: a qualitative exploration of participants’ experiences of ketamine-assisted psychotherapy for methamphetamine use disorder Frontiers in Psychiatry June 24, 2026
- Ketamine-assisted psychotherapy for treatment of an Asian American patient with post-traumatic stress disorder (PTSD): a case study Psychiatry Research Case Reports May 22, 2026
- The Emerging Neurobiology of Psychedelics: Critical Periods, Metaplasticity, and Extracellular Matrix Remodeling. Annual Review of Neuroscience July 1, 2026
Cites 82
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Ketamine use: a review Addiction July 21, 2011
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry March 29, 2019
and 77 more in the library