For decades, researchers have looked for ways to treat patients with treatment-resistant depression (TRD). Psilocybin, a psychedelic compound found in certain mushrooms, may be one answer, according to research published in the New England Journal of Medicine.1
A Phase II clinical trial demonstrated the feasibility of synthetic psilocybin monotherapy for up to 12 weeks for TRD patients. Given the promising results, the sponsor plans to begin Phase III trials by the end of 2023.
About the Trial
This 22-site global clinical trial was conducted between March 2019 and September 2021.
Researchers randomly assigned 233 adults with TRD to receive a single dose of a synthetic form of psilocybin at a dose of either 25 mg, 10 mg, or 1 mg. All patients also received psychological support. The 1 mg cohort served as the control group.
Participants completed a run-in period during which antidepressants and other medications affecting the central nervous system were gradually discontinued. During this period, each participant met with a therapist at least three times.
As the psilocybin was administered, participants listened to a specially designed music playlist and wore eyeshades to help direct attention internally. Once the psychedelic effects fully dissipated—after about six hours –the patients returned home.
Assessing the patients
The trial used the Montgomery-Åsberg depression rating scale (MADRS); the primary endpoint was the change in the MADRS total score from baseline to week three.
A global cohort of WCG independent raters—all experienced clinicians who underwent extensive training and calibration—administered the MADRS by telephone at baseline; on day two; and at weeks one, three (the primary endpoint assessment), six, nine and 12.
WCG also handled the statistical analysis of the data.
What Investigators Learned
The patients who received the 25 mg dose had significantly reduced MADRS scores compared to the 1 mg control group. There was no significant difference between the 10 mg dose and the 1 mg dose.
Here are some highlights:
- Significant three-week response: At week three, 37% of participants in the 25mg arm were responders, compared to 19% in the 10 mg group, and 18% in the 1 mg group. (The protocol defined “response” as a decrease of at least 50% from baseline in the MADRS total score.) Additionally, 29% of the 25 mg were in remission, compared to 9% in the 10 mg group, and 8% in the 1 mg group. (Remission was defined as a MADRS score of 10 or lower.)
- Sustained response: 23% of the patients who received a 25mg dose had a sustained response at week 12, compared to10.1% of those who received 1 mg (10.1%). (The protocol defines a “sustained response” as a week 3 response sustained through week 12.)
- Rapid onset: The maximum effect was seen the day after receiving the treatment. Standard antidepressants can take several weeks to reach maximum effect.
- Adverse events: Most (77%) of participants reported side effects that included headache, nausea, dizziness and fatigue. A few patients reported suicidal ideation and self-injurious behavior; this was significantly more common in the 25 mg and 10 mg groups.
Why it Matters
Like other psychedelics, psilocybin has the potential to address unmet needs for CNS disorders, including TRD. Over the last few years, research into the safety and efficacy of psilocybin has accelerated dramatically. This study — the largest psilocybin therapy clinical trial to date — represents an important step in understanding how it affects depression.
The stakes are high: An estimated 100 million people worldwide have treatment-resistant depression, and about half of those have difficulty with daily routines, facing impaired quality of life, job and role performance, and other significant challenges.
This Phase II study just a beginning. As the researchers conclude, “Longer and larger trials, including comparison with existing treatments for depression, are required to determine the efficacy and safety of psilocybin for treatment-resistant depression.”
Given the tremendous need, we can’t make that determination soon enough.
To learn more about WCG’s independent ratings services click here.
- Goodwin GM, Aaronson ST, Alvarez O, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine. 2022;387(18):1637-1648. doi: https://doi.org/10.1056/nejmoa2206443
Let’s discuss how you can improve signal detection on your CNS study
A short conversation will help assess your needs and how WCG can assist. To arrange a call with one of our CNS experts, simply fill out this form.