By Rich Haridy November 09, 2021
A demonstration of the conditions used in the psychedelic trialCompass Pathways
Early data from the largest trial to date testing psilocybin therapy for depression indicates the psychedelic treatment may be somewhat effective at reducing symptom severity. However, concerns over some adverse effects indicate there is more work to be done before psilocybin is ready for clinical approval.
Mental health care company Compass Pathways’ Phase 2B psilocybin therapy trial for treatment-resistant depression was granted Breakthrough Therapy designation by the US Food and Drug Administration (FDA) in late 2018. Although there have been larger trials examining the therapeutic potential of MDMA, it isn’t considered a classical psychedelic (unlike LSD, psilocybin, DMT or mescaline), making this the largest blinded control study completed to date exploring the efficacy of this kind of novel psychedelic-assisted therapy.
The company has now announced the first top-line results from its landmark trial, reporting a “rapid and sustained” response from just one dose of psilocybin accompanied by psychotherapy sessions. The results have yet to be peer-reviewed and published in a journal.
The trial recruited 233 patients with treatment-resistant depression who were randomly, and blindly, split into three dosage arms: 25 mg, 10 mg, and 1 mg. The 1-mg group essentially served as a placebo group, still receiving all the pre and post psychotherapy treatments. Depression was measured using the Montgomery–Åsberg Depression Rating Scale (MADRS), a widely-used method for calculating depression severity.
The trial tested a multi-week treatment protocol, with preparatory psychotherapy before a single active psilocybin session and several follow-up sessions in the weeks afterwards. The primary endpoint looked at the change in total MADRS score from baseline to three weeks after the psilocybin session.
A slide supplied by Compass Pathways showing the change in MADRS scores from baseline Compass Pathways
At week 3 the results indicate 29.1 percent of patients in the 25-mg psilocybin group were in remission, based on MADRS scores. This compared to 7.6 percent of the 1-mg placebo group in remission. By week 12 the study saw 26.6 percent of the 25-mg psilocybin group sustaining remission (21 out 79). Overall, the study saw an average 6.6-point greater reduction in MADRS scores from baseline to week 3 in the 25-mg psilocybin group compared to the 1-mg group.
A slide supplied by Compass Pathways showing the subjects achieving remission based on MADRS scores across the 12-week trial period
Suresh Muthukumaraswamy, a neuropsychopharmacologist working with psychedelics at the University of Auckland, sees the results released so far as mixed. And the press release from Compass Pathways announcing these results is far from clear.
“I would say the results are a mixed bag,” says Muthukumaraswamy in an email to New Atlas. “There are certainly some promising looking results in terms of efficacy but also some safety concerns around the number of SAEs [serious adverse events] (mostly suicidality). The durability of the response is also unknown.”
Five patients (6.3 percent) in the 25-mg group and six patients (8 percent) in the 10-mg group experienced at least one serious adverse event in the follow-up period after the psilocybin treatment. This compared to just one serious adverse event reported in the 1-mg placebo group.
These serious adverse events included suicidal ideation and suicidal behavior. Muthukumaraswamy says a 35-percent response rate and a 5-percent SAE rate means for every seven patients positively responding to the treatment, one person will experience serious negative outcomes.
An example of one of the rooms used in the psychedelic clinical trialCompass Pathways
Lars Christian Wilde, co-founder of Compass Pathways, noted in an investor call reporting the trial findings that this volume of adverse events was not unexpected as suicidal ideation is common in this kind of depression research.
“We’re dealing with a severe patient population, both in terms of patient severity and duration of their depressive episode,” Wilde says. “Unfortunately those events have to be expected.”
Compass Pathways say analysis of this Phase 2B data is ongoing, and the next steps will be to meet with the FDA in early 2022 to discuss design of the Phase 3 trials, which are hoped to begin later next year.
There are also a number of other ongoing Phase 2 trials testing psilocybin for a variety of conditions including major depressive disorder, alcoholism, anorexia, chronic pain, and cluster headaches. So undoubtedly there will be plenty more data to pore over as those trials deliver results in the coming months and years.
Muthukumaraswamy is a little more circumspect in his reading of the new data, suggesting lots more work is needed to home in on the most effective ways to administer these new psychedelic medicines.
“It looks to me like that there is going to need to be a bit of digging around in the data to work out how to optimize the trials / treatment / patient selections to improve both safety and efficacy,” he says. “This might take some time.”
Source: Compass Pathways
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