Multiple-Dose Psilocybin Treatments Show Promise for Treatment-Resistant Depression

Treatment-resistant depression is a form of major depressive disorder where a patient does not respond to traditional antidepressant medications. Several clinical trials have demonstrated promising results in relieving the symptoms of depression with psilocybin-assisted psychotherapy; however, this research has largely excluded patients with more complex presentations of the mental illness. As a result, the generalizability of prior trial results remains unclear.

In an effort to bridge this gap of scientific knowledge, a recent clinical trial has assessed the effects of psilocybin-assisted therapy on individuals with “high levels of treatment resistance, significant comorbidities, and both major depressive disorder and bipolar II disorder.” The randomized study found that greater antidepressant effects were linked to the administration of multiple psilocybin doses, thereby providing more justification for patients with more complicated presentations of depression in future psilocybin research.

Study setup and primary findings

All of the participants of the study were deemed as highly treatment-resistant, with all but one failing numerous forms of psychotherapy and a large quantity having failed more intensive treatments like ECT or ketamine infusions. The subjects were placed on a randomized waitlist for ethical considerations and to compare the effectiveness of the intervention to that of immediate treatment. By the end of the study, all participants received psilocybin-assisted psychotherapy. The participants either had one, two, or three sessions of psilocybin treatment with a fixed dose of 25mg in conjunction with psychotherapy sessions.

Following treatment, primary findings indicated that the patients who received immediate treatment demonstrated notable reductions in depression severity compared to those in the waitlist group. Individuals treated with multiple doses had even more pronounced effects. These results suggest a dose-responsive relationship where repeated psilocybin administration could enhance the therapeutic outcomes in treatment-resistant depression.

Some participants noted mild adverse effects, with the most common being headaches, dizziness, and nausea, but overall, psilocybin was deemed safe for use in individuals with more complex forms of major depressive disorder (1).

Further research

The results of the study provide a strong justification for including patients with more complex presentations of depression in future psilocybin trials. Nonetheless, future research will be needed to determine the optimal dosage strategies and long-term outcomes of treatment. 

Major depressive disorder impacts 21 million U.S. adults, and 30% of those individuals are treatment-resistant. The study’s findings advocate for the inclusion of more diverse patient populations in the future of psilocybin trials so that results are more applicable to a broader spectrum of individuals with depression, offering a novel therapy to those who have not had success with traditional treatments.

References

1. Rosenblat, Joshua D, Shakila Meshkat, Zoe Doyle, Erica Kaczmarek, Ryan M Brudner, Kevin Kratiuk, Rodrigo B Mansur, et al. 2024. “Psilocybin-Assisted Psychotherapy for Treatment Resistant Depression: A Randomized Clinical Trial Evaluating Repeated Doses of Psilocybin.” Med, February. https://doi.org/10.1016/j.medj.2024.01.005.