Psychedelic therapy no better than open-label antidepressants for depression, review finds

The question

When people know which treatment they are getting, does psychedelic-assisted therapy improve depression more than standard antidepressants do?

What they did

Researchers searched PubMed in March 2024 for trials in adults with major depression (without other major conditions, without psychosis, treated as outpatients). They included 24 trials from 619 records: 8 psychedelic-assisted therapy trials (249 patients) and 16 open-label antidepressant trials (7921 patients). Because participants in psychedelic trials almost always guess correctly whether they got the drug, the authors compared psychedelic therapy against antidepressant trials where everyone also knew what they were taking. They also drew on an existing review of 144 blinded antidepressant trials (31 792 patients) to see how blinding changes results, and measured the average change in depression scores within each treatment arm on the 17-item Hamilton Depression Rating Scale.

What they found

Psychedelic-assisted therapy was not more effective than open-label antidepressants. The estimated difference was 0.3 points on the Hamilton scale, slightly favouring open-label antidepressants (95% confidence interval -1.39 to 1.98; P = .73) — a result consistent with no real difference. Open-label antidepressant trials showed better outcomes than blinded antidepressant trials, by 1.3 points (95% CI, 0.07 to 2.51; P = .04). No such gap appeared between blinded and open-label psychedelic trials (0.67; 95% CI, -3.08 to 1.73; P = .58), which the authors take as evidence that psychedelic trials are effectively open label regardless of their design.

The fine print

This compares results across separate studies rather than testing the two treatments head-to-head in the same randomized trial, so differences in patients, settings and eras could explain some of the findings. The psychedelic side rests on just 8 trials and 249 patients, far fewer than the antidepressant data. Only PubMed was searched, the analysis looked at change within treatment arms rather than against a control, and the abstract reports no side-effect or long-term follow-up data. This summary is based on the abstract alone.

What it means

Once you compare like with like — treatments where patients know what they are receiving — psychedelic-assisted therapy did not outperform standard antidepressants in these depression trials. It is a caution against strong claims of superiority, and a reminder that blinding problems make psychedelic trial results hard to interpret.

Evidence grade: Moderate. A systematic review and meta-analysis of trials, but the key comparison is indirect — pooling results from separate psychedelic and antidepressant studies rather than randomizing people head-to-head.

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