Other · 2026
A review of psychedelics and ketamine for depression that has not responded to treatment
- Original title
- Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations.
- Authors
- Estela-Fernandez CA, Mohamed Yousif Elsheikh R, Beatrice DB, et al.
- Journal
- Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater, 2026
- Molecules
- Psilocybin, Ketamine, Esketamine, Ayahuasca
- Conditions
- Treatment-resistant depression, Depression
- Evidence grade
- Low
- Source
- Read the original paper
The question
Can psychedelic drugs and ketamine-type drugs help people with treatment-resistant depression, and how might they work in the brain?
What they did
The authors searched the published literature on several psychedelic and psychedelic-adjacent drugs, drawing on both laboratory (preclinical) research and human clinical studies. They focused on treatment-resistant depression, meaning major depression that has not improved after standard antidepressant treatment. They summarized proposed biological mechanisms alongside reported clinical results. The abstract does not describe a formal systematic search method or a pooled analysis of data.
What they found
The authors report that far more laboratory studies than clinical studies exist in patients with treatment-resistant depression. Proposed mechanisms include action on serotonin receptors, a surge in the brain chemical glutamate, monoamine release, increased neuroplasticity (the brain’s ability to form new connections), changes in cortical-limbic circuits, and epigenetic changes. Psilocybin, ketamine and esketamine were described as the most studied. The review states that psilocybin-assisted therapy produced short-term symptom improvement that could last weeks to months, that ketamine given by vein, under the skin or by mouth had rapid effects on depressive symptoms without reducing cognitive function, that esketamine improved functioning and productivity, and that ayahuasca showed fast and sustained effects with higher remission rates and good safety.
The fine print
The abstract reports no numbers: no sample sizes, effect sizes, dose ranges or follow-up lengths, so readers cannot judge how strong the underlying evidence is. As a narrative review without a described systematic method, it is open to selective citation, and the authors themselves note that clinical studies in treatment-resistant depression are few. The claim that these drugs have “superior mechanisms” is an interpretation, not a measured outcome. This summary is based on the abstract alone.
What it means
The review argues that psilocybin, ketamine, esketamine and ayahuasca show promise for depression that has not responded to standard treatment, but the authors conclude that large, well-designed trials are still needed before these become standard care.
Evidence grade: Low. This is a narrative review that summarizes other studies without a stated systematic search or pooled statistical analysis, so it carries less weight than a systematic review or meta-analysis.
This summary is based on the study’s published abstract.