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

Ana Malta Gomes, Filipa Novais

Summary & key facts

Researchers collected and analyzed eight studies involving about 420 people who had depression that did not improve after usual treatments. They compared ketamine combined with psychotherapy to ketamine alone. Overall, people who got the combined treatment had bigger drops in depressive symptoms. There are also early signs it might help related problems like anxiety, PTSD, and chronic pain. But the studies were small, used different ways of giving the treatment, and followed people only for a short time, so we cannot be sure yet how well the combined approach works long term or for everyone.

Key facts:

The review combined results from eight studies with about 420 people who had treatment-resistant depression.
Across those studies, ketamine together with psychotherapy led to larger reductions in depressive symptoms than ketamine given without psychotherapy.
Some studies showed early benefits for other problems that happened at the same time, such as anxiety, post-traumatic stress symptoms, and chronic pain.
Most studies were small and used different treatment methods, which makes it hard to compare results or draw firm conclusions.
Many studies only checked people for a short time after treatment, so we do not know how long any benefits last.
The reviewers said larger, higher-quality studies with consistent methods are needed before clinicians can know how best to use ketamine plus therapy and who it helps most.

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.

Topics

Substances

Ketamine

Conditions & symptoms

Anxiety Chronic Pain Depression PTSD Anxiety or worry Chronic pain Lack of energy or motivation Poor sleep Sadness or low mood

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