Effects of psilocybin with psychological support on anhedonia in treatment-resistant depression: A randomized controlled pilot trial.
Andrew M Novick, Tiffany M Love, Rachel L Johnson et al.
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In 30 seconds
This randomized, double-blind, placebo-controlled pilot trial assessed psilocybin with psychological support for anhedonia in 20 participants with treatment-resistant major depressive disorder. The primary outcome, change in Dimensional Anhedonia Rating Scale (DARS) score at week 1, did not differ significantly between the 25 mg and 1 mg groups (between-group difference, 11.2; 95% CI, -1.0 to 23.3; p = 0.073). Secondary results favored 25 mg for DARS at week 8 and for overall depression severity at weeks 1 and 8, but the authors state that larger trials are needed to confirm potential benefits.
Key findings
- The primary week 1 DARS outcome was not statistically significant: between-group difference, 11.2 (95% CI, -1.0 to 23.3; p = 0.073).
- At week 8, DARS improvement favored 25 mg: difference, 14.7 (95% CI, 2.5 to 26.8; p = 0.018).
- MADRS improvement favored 25 mg at week 1 (-11.9; 95% CI, -19.2 to -4.5; p = 0.002) and week 8 (-11.6; 95% CI, -19.0 to -4.2; p = 0.002).
- SHAPS improvement favored 25 mg at week 1, but not week 8.
Why it matters
Anhedonia can be resistant to available treatments, and this trial directly evaluated it rather than relying only on overall depression severity. The nonsignificant primary result tempers interpretation, while favorable secondary outcomes provide a rationale for further study. The findings illustrate why secondary signals in a small pilot trial should not be treated as established efficacy.
What to keep in mind
This was a pilot trial with 20 participants, and the primary anhedonia outcome was not statistically significant; favorable findings were on secondary outcomes.