A review of psychedelics and ketamine as fast-acting treatments for depression

The question

Can psychedelic drugs and ketamine-type drugs fill the gap left by standard antidepressants for people whose depression does not respond to first-line treatment?

What they did

This is a review chapter, not a new study. The authors summarize two decades of clinical research on two groups of drugs for major depressive disorder and treatment-resistant depression: ‘typical’ serotonergic psychedelics such as psilocybin and ayahuasca, and ‘atypical’ glutamate-acting drugs such as ketamine and esketamine. They trace the clinical development path that, in their account, led to psilocybin and esketamine being brought to market for depression, and they discuss how these drugs may work and how they should be studied.

What they found

The authors note that most people with depression are first offered SSRIs or SNRIs, that many respond poorly, and that roughly 30% fail to respond at all, which is how treatment-resistant depression arises. They argue that both drug classes act quickly, often immediately, and that the antidepressant effect can outlast the time the drug is present in the brain, suggesting the benefit comes from downstream changes in brain circuits rather than the drug itself lingering. They also flag a core research problem: the acute mind-altering effects of psilocybin and the dissociative effects of esketamine make it very hard to keep participants and researchers unaware of who received the active drug, which weakens placebo comparisons.

The fine print

This is a narrative review, so the authors chose which evidence to discuss and no trials were pooled or formally appraised. The abstract reports no trial sizes, doses, effect sizes or safety data, and gives only one number (about 30% non-response). Claims about which treatments are marketed and for which conditions vary by country and are not detailed here. This summary is based on the abstract alone.

What it means

Experts in the field see fast-acting treatments for depression as an important development, but the same abstract highlights that blinding problems make the size of the true drug effect hard to pin down.

Evidence grade: Very low. This is a narrative book-chapter review: it summarizes the field in the authors’ own words without a systematic search, pooled data or reported participant numbers.

This summary is based on the study’s published abstract.