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

Treatment-resistant depression (TRD) shows minimal improvement after two or more antidepressant trials. Ketamine-assisted psychotherapy (KAP) combines the rapid antidepressant effects of ketamine with psychotherapy to improve and sustain outcomes. A systematic review of eight studies involving 421 participants found that KAP significantly reduces depressive symptoms compared to ketamine alone. Preliminary evidence also suggests KAP may help with PTSD, anxiety, and chronic pain. However, small sample sizes, varying protocols, short follow-ups, and risk of bias limit firm conclusions. The findings indicate KAP is promising for TRD, but larger, high-quality trials are needed to confirm effectiveness and establish standard protocols.

Study at a glance

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.