Psilocybin-assisted therapy effective on major depressive disorder

Psilocybin-assisted therapy is effective in producing large, rapid, and sustained antidepressant effects among patients with major depressive disorder (MDD), results of a randomized, waiting-list controlled clinical trial have shown.

“This study data expands the findings of previous studies involving patients with cancer and depression as well as patients with treatment-resistant depression, suggesting that psilocybin may be effective in the much larger patient population with MDD,” concluded the researchers. [JAMA Psychiatry 2020, doi: 10.1001/jamapsychiatry.2020.3285]

“Further studies are needed with active treatment of placebo controls and in larger and more diverse populations.”

In the study, 27 participants with an MDD diagnosis (GRID-Hamilton Depression Rating Scale [GRID-HAMD] ≥17), not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were randomized to receive immediate psilocybin treatment, consisting of two psilocybin sessions (session 1: 20 mg/70kg, session 2: 30mg/70kg) administered in opaque gelatin capsules with approximately 100 mL water, or delayed psilocybin treatment (ie, an 8-week delay) in the context of supportive psychotherapy lasted approximately 11 hours between August 2017 and April 2019. Participants were assessed for depression severity at baseline and weeks 1 and 4 after the intervention for the immediate treatment group, and weeks 5 and 8 after enrollment for the delayed treatment group.

At baseline, the completion rate of the intervention and week 1 and week 4 post-session assessments was 89 percent (24 participants; mean age, 39.8 years; female, 67 percent), with mean baseline GRID-HAMD score of 22.8. Among the cohort, 13 participants and 11 participants received immediate and delayed treatment, respectively.

Overall, 67 percent and 71 percent of participants at week 1 and week 4 had a clinically significant response to the intervention (ie, ≥50 percent reduction in GRID-HAMD score), whilst 58 percent and 54 percent of all participants at week 1 and week 4 were in remission (≤7 GRID-HAMD score). 

Participants in the immediate treatment group had statistically significantly lower mean GRID-HAMD scores at week 1 and 4 (8.0 and 8.5) post-session follow-ups, compared with the corresponding time points of week 5 and 8 (23.8 and 23.5) in the delayed treatment group, with effect size of Cohen d=2.2 at week 5 (95 percent confident interval [Cl], 1.4 to 3.0; p<0.001) and Cohen d=2.6 at week 8 (95 percent Cl, 1.7 to 3.6; p<0.001). 

A rapid decrease in mean depression score, measured by the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR), was observed in participants from baseline to day 1 after psilocybin session 1 (16.7 vs 6.3; Cohen d=3.0; 95 percent CI, 1.9 to 4.0; p<0.001), and the substantial decrease remained statistically significant through the week 4 after session 2 (6.0; Cohen d=3.1; 95 percent Cl, 1.9 to 4.2; p<0.001).