Table 2. Overall Summary of Primary, Secondary, and Select Exploratory Efficacy Outcomes.
| Outcome | Mean change from baseline (95% CI)a | Mean difference (95% CI)a | P value | |
|---|---|---|---|---|
| Psilocybin (n = 51) | Niacin (n = 53) | Psilocybin vs niacin | ||
| MADRS total scoreb | ||||
| Day 2 | −2.7 (−4.1 to −1.3) | −2.7 (−4.1 to −1.3) | −0.1 (−2.1 to 1.9) | .95 |
| Day 8 (key secondary outcome) | −17.8 (−21.1 to −14.6) | −5.8 (−9.1 to −2.6) | −12.0 (−16.6 to −7.4) | <.001c |
| Day 15 | −18.0 (−21.3 to −14.7) | −6.9 (−10.3 to −3.5) | −11.1 (−15.8 to −6.3) | <.001 |
| Day 29 | −19.2 (−22.6 to −15.8) | −5.5 (−9.0 to −2.0) | −13.7 (−18.6 to −8.8) | <.001 |
| Day 43 (primary outcome) | −19.1 (−22.7 to −15.5) | −6.8 (−10.5 to −3.1) | −12.3 (−17.5 to −7.2) | <.001c |
| SDS mean scoreb | ||||
| Day 8 | −3.85 (−4.60 to −3.10) | −1.49 (−2.27 to −0.72) | −2.36 (−3.46 to −1.26) | <.001 |
| Day 15 | −3.97 (−4.73 to −3.21) | −1.76 (−2.56 to −0.97) | −2.21 (−3.33 to −1.09) | <.001 |
| Day 29 | −4.26 (−5.08 to −3.45) | −1.78 (−2.64 to −0.93) | −2.48 (−3.68 to −1.28) | <.001 |
| Day 43 (secondary outcome) | −4.07 (−4.88 to −3.26) | −1.76 (−2.62 to −0.91) | −2.31 (−3.50 to −1.11) | <.001c |
| Other secondary outcomes | No./total No. (%)d | No./total No. (%)d | Difference (95% CI)e | |
| Sustained depressive symptom responsef | 20/48 (41.7) | 5/44 (11.4) | 30.3 (13.5 to 47.1)g | .002c,d |
| Sustained depressive symptom remissionh | 12/48 (25.0) | 4/44 (9.1) | 15.9 (1.0 to 30.8)i | .05d |
Abbreviations: MADRS, Montgomery-Asberg Depression Rating Scale; SDS, Sheehan Disability Scale.
Mixed model for repeated measures with an unstructured covariance structure adjusted for baseline score, site, sex, and treatment-resistant depression. Negative values indicate an improvement in symptom severity. For additional information, see footnote c in Table 1.
All outcomes are exploratory unless otherwise noted.
Statistically significant based on sequential testing procedure.
Restricted to participants in the intent-to-treat population with MADRS assessments at baseline, and days 8, 15, 29, and 43 after baseline.
P value from logistic regression model adjusted for sex and treatment-resistant depression, predicting odds of response or remissions for psilocybin compared with niacin. Wald 95% CIs are provided for difference in difference in response and remission rates.
Sustained depressive symptom response is defined as ≥50% reduction from baseline central rater MADRS total score at each of the postdose assessments on days 8, 15, 29, and 43.
Odds ratio, 5.60 (95% CI, 1.87-16.74).
Sustained depressive symptom remission is defined as a central rater MADRS total score ≤10 at each of the postdose assessments on days 8, 15, 29, and 43.
Odds ratio, 3.37 (95% CI, 0.99-11.47).