NEW ORLEANS –
“This is easily the largest study of a psychedelic drug employing modern randomized controlled trial methodology [with] 22 sites and 10 countries, so it’s not your typical phase 2 trial,” the study’s lead author, Guy M. Goodwin, MD, emeritus professor of psychiatry at the University of Oxford, England, said in an interview.
Dr. Guy M. Goodwin
“Importantly, 94% of the patients in the study were psilocybin naive, which is very important for generalizability,” Dr. Goodwin noted.
Long used as psychedelic ‘magic mushrooms,’ psilocybin has gained increased interest in psychiatry in recent years as a potential treatment for severe depression after showing benefits in patients with life-threatening cancers and others with major depressive disorder (MDD).
To put the therapy to test in a more rigorous, randomized trial, Dr. Goodwin and colleagues conducted the phase 2b study of a proprietary synthetic formulation of psilocybin, COMP360 (COMPASS Pathways), recruiting 233 patients with treatment-resistant depression at 22 centers.
The study was presented at the annual meeting of the American Psychiatric Association.
After a 2-week washout period following the discontinuation of antidepressants, the patients were randomized to one of three groups: A single dose of 25 mg (n = 79), 10 mg (n = 75), or a subtherapeutic comparison of 1 mg (n = 79).
The psilocybin was administered in the presence of specially trained therapists who provided psychological support before, during, and after the 6- to 8-hour session.
Patients were then asked to refrain from antidepressant use for at least 3 weeks following the session, and had periodic follow-up for 12 weeks.
For the primary endpoint, those in the 25-mg group, but not the 10-mg dose, showed a significantly greater reduction in depression from baseline versus the 1-mg group on the Montgomery-Åsberg Depression Rating Scale at week 3 (MADRS; -6.6; P < .001).
The benefit was observed at day 2 and week 1 following administration, “confirming the rapid-acting character of the effect,” the investigators reported.
Sustained responses, defined as at least a 50% change from baseline in MADRS total score, were further observed up to week 12 among 20.3% in the 25-mg group and among 5.3% in the 10-mg groups versus 10.1% in the 1-mg group.
On the day of psilocybin treatment, the treatment-emergent side effects that were reported were headache, nausea, and dizziness, with event rates of 83.5% in the 25-mg group, 74.7% in the 10-mg group, and 72.2% in the 1-mg group.
One participant in the 25-mg group experienced acute anxiety and was treated with lorazepam.
The incidence of treatment-emergent serious adverse events from day 2 to week 3 was 6.3% (five patients) in the 25-mg group, 8.0% (six patients) in the 10-mg group, and 1.3% (one patient) in the 1-mg group.
Serious AEs included suicidal ideation and intentional self-injury among two patients each in the 25-mg group, while in the 10-mg group, two had suicidal ideation and one had hospitalization for severe depression.
There were no significant differences between the groups in terms of vital signs or clinical laboratory tests.
Of note, two patients in the 25-mg group had a change from baseline in QTcF >60 msec on day 2. For one patient, the increase was within normal range, and the other had a QTcF interval duration >500 msec on day 2, but levels returned to normal by day 9.