Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.

A single 25 mg dose of synthetic psilocybin (COMP360) given alongside psychological support to adults with treatment-resistant depression who continued taking a selective serotonin reuptake inhibitor led to a mean reduction of 14.9 points on the Montgomery-Åsberg Depression Rating Scale at three weeks. Twelve of nineteen participants (63.2%) experienced mild treatment-emergent adverse events that resolved the same day, with no serious events or increased suicidal ideation. Response and remission occurred in 8 participants (42.1%). The authors suggest larger controlled trials are needed to determine whether this approach can benefit patients who cannot safely withdraw from antidepressants.

Study at a glance

Abstract

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD. Participants received a single 25 mg dose of psilocybin alongside psychological support and were followed-up for 3 weeks. The primary efficacy end point was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from Baseline at Week 3. Secondary end points were safety, including treatment-emergent adverse events (TEAEs), the proportion of responders and remitters at Week 3, and the change from Baseline to Week 3 in Clinical Global Impression-Severity (CGI-S) score. Nineteen participants were dosed and the mean Baseline MADRS total score was 31.7 (SD = 5.77). Twelve (63.2%) participants had a TEAE, most of which were mild and resolved on the day of onset. There were no serious TEAEs or indication of increased suicidal ideation or behavior. At Week 3, mean change from Baseline in MADRS total score was -14.9 (95% CI, -20.7 to -9.2), and -1.3 (SD = 1.29) in the CGI-S. Both response and remission were evident in 8 (42.1%) participants. Larger, comparator-controlled trials are necessary to understand if this paradigm can optimize treatment-outcome where antidepressant drug withdrawal would be problematic.