Systematic review · 2026
Review of ketamine combined with psychotherapy for hard-to-treat depression
- Original title
- Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review.
- Authors
- Simpson RJ, Juruena MF
- Journal
- Psychopharmacology, 2026
- Molecules
- Ketamine
- Conditions
- Treatment-resistant depression, Depression
- Evidence grade
- Low
- Source
- Read the original paper
The question
Does pairing ketamine treatment with structured psychological support (ketamine-assisted psychotherapy) help people whose depression has not responded to standard treatments?
What they did
Researchers searched four large research databases for studies combining ketamine with psychotherapy for depression. The search returned 768 records, and screening following standard review guidelines (PRISMA) left 11 studies that met the inclusion criteria. The authors grouped these studies into two types: structured, protocol-based therapy programs and more individualized, experience-focused approaches.
What they found
Across all 11 studies, ketamine-assisted psychotherapy was associated with reductions in depression symptoms, and in some studies improvements lasted up to six months. But only three of the studies included a comparison (control) group, and in those three there was no significant difference between ketamine-assisted psychotherapy and the control condition. The authors noted that differences in treatment protocols, outcome measures and study designs made it hard to draw firm conclusions or explain how the approach might work.
The fine print
Only 11 studies were included and the abstract does not report how many people took part in total. Most studies lacked a control group, so improvement could reflect the ketamine alone, the passage of time, or expectation rather than the added psychotherapy. The three controlled studies found no advantage over their comparison conditions. This summary is based on the abstract only.
What it means
Adding psychotherapy to ketamine treatment is an appealing idea, but the existing studies are too few, too varied and too rarely controlled to show that the therapy component adds benefit on its own.
Evidence grade: Low. A systematic review of only 11 mostly uncontrolled studies with widely differing methods, and no pooled statistical analysis.
This summary is based on the study’s published abstract.