THURSDAY, March 19, 2026 (HealthDay News) -- Psychedelic-assisted therapy (PAT) is no more effective than traditional antidepressants (TADs) for treatment of major depression, according to a review published online March 19 in JAMA Psychiatry.
Zachary J. Williams, M.D., Ph.D., from the University of California in Los Angeles, and colleagues conducted a systematic literature review to examine the comparative effectiveness of PAT versus open-label TADs for the treatment of major depression. The mean within-arm effect from baseline to primary end point (patient improvement between PAT and open-label TAD trials on the 17-item Hamilton Depression Rating Scale) was compared following predefined hypotheses. The potential role of blinding was assessed by comparing the within-arm effect of blinded versus open-label trials in both PAT and TADs. Twenty-four studies met the inclusion criteria.
The researchers found that PAT (eight trials; 249 patients) was no more effective than open-label TAD treatment (16 trials; 7,921 patients), contrary to the first of three hypotheses. Compared with blinded treatment, open-label TADs were associated with better outcomes, with an estimated difference of 1.3; the same difference was not seen for PAT.
"Unblinding is the defining methodological problem of psychedelic trials. What I wanted to show is that even if you compare psychedelics to open-label antidepressants, psychedelics are still much better," lead author Balázs Szigeti, Ph.D., from the University of California in San Francisco, said in a statement. "Unfortunately, what we got is the opposite result -- that they are the same, which is very surprising given the enthusiasm around psychedelics and mental health."
One author disclosed ties to Roche.