, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.