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Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis

Summary

This study compared psychedelic drugs (psilocybin, LSD, MDMA, ayahuasca) with the antidepressant escitalopram for treating depression. Researchers analyzed 19 clinical trials and found that while psilocybin showed promise, its actual effectiveness was smaller than previously reported due to blinding issues in earlier studies. High-dose psilocybin performed better than escitalopram in some comparisons, but had a similar small effect size to current antidepressants.

Background

Psychedelics have shown potential for treating depression, but previous meta-analyses reported large effect sizes (1.37-3.12) compared to antidepressants (0.3), raising concerns about overestimation due to unsuccessful blinding in psychedelic trials.

Objective

To evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics (psilocybin, LSD, MDMA, ayahuasca) and escitalopram for depressive symptoms through systematic review and Bayesian network meta-analysis, accounting for differences in placebo response between psychedelic and antidepressant trials.

Results

Placebo response in psychedelic trials was significantly lower than in antidepressant trials (mean difference -3.90). Only high-dose psilocybin showed superiority over placebo in antidepressant trials, but effect size decreased from large (0.88) to small (0.31) when compared to antidepressant placebo. High-dose psilocybin exceeded the minimal important difference when compared to escitalopram 10mg and 20mg.

Conclusion

While high-dose psilocybin showed potential for treating depressive symptoms, its standardized mean difference (0.31) was similar to current antidepressants (0.3), suggesting a small effect size. Previous psychedelic studies may have overestimated efficacy due to blinding issues. Improved blinding methods are needed to accurately assess psychedelic efficacy.
  • Published in:BMJ,
  • Study Type:Systematic Review and Bayesian Network Meta-analysis,
  • Source: PMID: 39168500; DOI: 10.1136/bmj-2023-078607
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