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Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression: a Systematic Review

Ana Malta Gomes, Filipa Novais

Current Treatment Options in Psychiatry May 5, 2025 DOI: 10.1007/s40501-025-00346-z (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Sample size 421
Population Patients with treatment-resistant depression
Interventions Ketamine-assisted psychotherapy Ketamine monotherapy
Topics Depression Ketamine Esketamine Psychedelic-assisted therapy
Keywords Neurology Depression economics Psychotherapist Cognition
Citations 3
Key findings Ketamine-assisted psychotherapy significantly reduces depressive symptoms in treatment-resistant depression compared to ketamine monotherapy, though methodological limitations prevent definitive conclusions.

Abstract

Abstract Purpose of the review Treatment-resistant depression (TRD) is a challenging condition characterized by minimal improvement despite two or more antidepressant trials. Ketamine-assisted psychotherapy (KAP) integrates the rapid antidepressant effects of ketamine with psychotherapy to enhance and sustain therapeutic outcomes. This systematic review evaluates the effectiveness of KAP in reducing depressive symptoms in TRD compared to ketamine monotherapy. Recent findings Eight studies, including 421 participants, were analyzed, highlighting significant reductions in depressive symptoms with KAP. Preliminary evidence suggests that KAP may also alleviate comorbid conditions such as PTSD, anxiety, and chronic pain. However, methodological limitations, including small sample sizes and variability in intervention protocols, restrict the ability to draw definitive conclusions. Risk of bias and short follow-up durations were common across studies. Summary KAP shows promise as an effective intervention for TRD, potentially enhancing the antidepressant effects of ketamine. Despite these encouraging findings, the variability in study designs and limited long-term data emphasize the need for larger, high-quality trials to confirm its efficacy and establish standardized protocols.

Comparable studies

Other systematic reviews and meta-analyses on ketamine and psychedelic-assisted therapy, most cited first.

Study Year Design Participants
A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review. Adults with treatment-resistant depression 2024 Systematic review
Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome. Patients with depression or substance use disorder 2024 Systematic review and meta-analysis n = 654
Ketamine and Ketamine-Assisted Psychotherapy for Psychiatric and Existential Distress in Patients with Serious Medical Illness: A Narrative Review. Patients with serious medical illness in a palliative care setting 2025 Systematic review
Psychedelic-Assisted Therapies for Psychosocial Symptoms in Cancer: A Systematic Review and Meta-Analysis Adults with cancer 2025 Systematic review and meta-analysis n = 455
How Do People Who Undergo Ketamine Treatment for a Psychiatric Problem Subjectively Experience This Intervention? A Meta-Synthesis of Qualitative Studies. People who received ketamine treatment for a psychiatric problem 2025 Systematic review and thematic meta-synthesis n = 24

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