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.
Citations in the library
Cited by 4
- Interdisciplinary, Delphi-driven consensus guidelines on the use of intravenous ketamine infusions for depressive disorders from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3). Journal of Affective Disorders May 16, 2026
- A Blueprint for Implementing Ketamine-Assisted Psychotherapy in Palliative Care: Design, Process, and Treatment Patterns of a Real-World Clinical Program. Journal of Palliative Medicine March 1, 2026
- Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample. Journal of Affective Disorders February 4, 2026
- Psychoactive and Neurobiological Effects of Ketamine in Humans: A Scoping Review of Clinical Evidence. Journal of Clinical Medicine July 29, 2026
Cites 15
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy Journal of Psychoactive Drugs March 15, 2019
- How do psychedelics work? Current Opinion in Psychiatry 2019
- Ketamine and the Future of Rapid-Acting Antidepressants Annual Review of Clinical Psychology February 9, 2021
- An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression. Frontiers in Psychiatry November 24, 2021
and 10 more in the library