Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review

Summary & key facts

This paper looked at all studies up to 2025 that combined ketamine with talking therapy, called ketamine-assisted psychotherapy. The authors found 64 articles covering 72 studies. Many reports were positive and suggested benefits across several mental health problems, but only a small number of the studies were the careful kind that randomly assign people to different treatments. Because the studies used very different methods and so few were well controlled, we still do not know for sure whether adding psychotherapy makes ketamine work better or how to best do the combined treatment.

Key facts:

• The review included 64 articles that described 72 studies of ketamine plus psychotherapy published up to 2025.
• Only about 11 of those studies were carefully controlled trials where people were randomly assigned to different treatments.
• Researchers grouped the types of psychotherapy into broad styles, such as psychoanalytic, behavioral, humanistic, cognitive-behavioral, and mixed or integrative approaches.
• Reports suggested benefits across several diagnoses, including major depression, posttraumatic stress disorder, obsessive-compulsive disorder, substance use disorders, and eating disorders.
• Compared to psychotherapy alone, combining ketamine with psychotherapy was often reported to increase engagement in treatment, reduce symptoms, and extend how long benefits lasted.
• Only two studies actually randomized the kind of psychotherapy used with ketamine. Neither showed that adding psychotherapy provided extra benefit, and one trial that also randomized ketamine found no clear interaction between drug and therapy.
• Because the studies used many different methods and few had a proper psychotherapy control group, the authors say we cannot draw firm conclusions about whether psychotherapy adds real extra benefit or creates a synergy with ketamine.
• The paper concludes that more well-controlled trials are needed to test whether therapy adds to ketamine’s effects and to find the best ways to combine them.

Abstract

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Topics

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Clinical psychology Clinical trial Hypnosis MEDLINE Mental health Psychiatry Psychology Psychotherapist Test (biology) Therapeutic relationship Validation test

Substances

Ketamine

Conditions & symptoms

Depression Eating Disorder Obsessive-Compulsive Disorder PTSD Substance abuse disorder Addiction or harmful habbits Sadness or low mood