Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life.

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints. METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function. RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures. LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin. CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

Will psilocybin lose its magic in the clinical setting?

Psilocybin as a novel treatment for depression is garnering a lot of attention from both the mainstream media and the academic community. Although phase 3 trials are only just beginning, we feel that it is important for clinicians to consider what psilocybin-assisted psychotherapy might look like in the clinical setting. In this narrative review article we have considered the difficulties that may arise as psilocybin emerges from the research setting, which may hamper its progress towards becoming a licenced medication. Psilocybin has its own unique challenges: the expectation patients come to dosing with having read overwhelmingly positive media; patient suggestibility under the influence of psilocybin and requirement for specialised therapists to name a few. We have also made some recommendations for measures that should be taken in both the phase 3 trials and with clinicians to try and minimise some of the issues raised. In doing so our hope is that psilocybin will continue towards becoming a licenced medication that suitable patients are able to access with relative ease. Practicing psychiatrists need to have an awareness of the potential pitfalls of psilocybin as they will be responsible for prescribing it in the future.