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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 Peer reviewed DOI: 10.1007/s40501-025-00346-z via OpenAlex

Summary

Ketamine-assisted psychotherapy (KAP) may effectively reduce depressive symptoms in individuals with treatment-resistant depression (TRD), as suggested by a systematic review of eight studies involving 421 participants. KAP not only appears to enhance the antidepressant effects of ketamine but may also help alleviate conditions like PTSD, anxiety, and chronic pain. However, methodological limitations such as small sample sizes and risk of bias hinder definitive conclusions, highlighting the need for larger, high-quality trials.

Study at a glance

Design systematic review
Sample size 421
Population individuals with treatment-resistant depression
Key finding KAP shows promise as an effective intervention for TRD, potentially enhancing the antidepressant effects of ketamine.

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.

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