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

Ana Malta Gomes, Filipa Novais

Summary & key facts

This review looked at studies of ketamine-assisted psychotherapy, which means giving ketamine together with talking therapy, for people whose depression did not get better after at least two antidepressants. The authors found eight studies with about 420 people and saw that the combined treatment usually reduced depressive symptoms more than ketamine alone. There was early evidence it might also help symptoms of post-traumatic stress, anxiety, and chronic pain. But the studies were small, used different ways of doing the treatment, often had risk of bias, and did not check people for very long. That means the approach looks promising but we need larger, higher-quality trials and standard methods before we can be sure how well it works and how long benefits last.

Key facts:

Ketamine-assisted psychotherapy means using ketamine together with psychotherapy, not ketamine by itself.
The review combined results from eight studies that included about 420 people with depression that had not improved after at least two antidepressants.
Across those studies, adding psychotherapy to ketamine led to bigger drops in depressive symptoms than ketamine alone.
Some studies reported early signs that the combined approach might also reduce symptoms of post-traumatic stress, anxiety, and chronic pain.
Common problems in the studies were small numbers of people, different ways of giving the treatment, short follow-up times, and risk of bias in the study designs.
Because of those limits, the reviewers said larger and better trials are needed to confirm the benefits and to agree on standard treatment methods.

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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