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

Summary & key facts

Researchers looked at all studies up to 2025 that combined ketamine with talk therapy for mental health problems. They grouped the kinds of therapy used and counted how many studies existed. Overall, many reports said the combination helped across different conditions, but there were few high-quality trials and the studies were very different from each other. That means we cannot be sure yet how much the talk therapy adds to ketamine, or which therapy methods work best. More well-controlled research is needed.

Key facts:

• The review looked at 64 published articles that described 72 separate studies of ketamine plus psychotherapy.
• Only 11 of those studies were randomized controlled trials, which are the most reliable kind of clinical test.
• Researchers sorted the psychotherapies into groups like psychoanalytic, behavioral, humanistic, cognitive-behavioral, integrative, and other; the largest single group was the 'other' category with about 24 studies.
• Reports in the studies suggested the combination helped different diagnoses, including major depression, post-traumatic stress disorder, obsessive-compulsive disorder, substance use disorders, and eating disorders.
• Compared to giving psychotherapy alone, ketamine plus psychotherapy was reported to improve how well people stayed in treatment, reduce symptoms more, and lengthen how long benefits lasted in several studies.
• Only two studies actually randomized which kind of psychotherapy people got while receiving ketamine, and neither found clear extra benefit from adding psychotherapy in that design.
• Because the methods and therapies varied a lot and few trials compared psychotherapy directly, the evidence does not yet prove that psychotherapy adds benefit or that the two work together in a special way.
• The authors say we need more well-controlled trials to test if psychotherapy adds anything to ketamine and to find which therapy approaches and schedules work best.

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