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

Summary & key facts

Nineteen adults with treatment-resistant depression stayed on their usual antidepressant medicine and were given a single 25 mg dose of a lab-made psilocybin called COMP360 alongside psychological support. They were checked for three weeks. On average their depression scores fell by about 15 points and about eight people, roughly 40%, met criteria for both response and remission at three weeks. About 12 people had side effects, but most were mild and cleared up the same day. There were no serious safety problems and no sign of increased suicidal thoughts. This was a small, open study with no comparison group, so bigger controlled trials are needed to know if these results hold up.

Key facts:

• Nineteen adults with treatment-resistant depression took part in the study.
• Participants kept taking a common type of antidepressant called an SSRI while receiving a single 25 mg dose of lab-made psilocybin (COMP360) with psychological support.
• Researchers followed people for three weeks after the dose to check safety and changes in depression.
• Average depression score at the start was about 32 on the scale used, and the average drop at three weeks was about 15 points.
• Eight people, about 40%, met criteria for both response and remission at three weeks.
• Twelve people reported new or worsened symptoms after the dose; most of those effects were mild and went away the same day.
• There were no serious adverse events and no indication of increased suicidal thoughts or behavior during the three weeks.
• The study was small and open-label, meaning everyone knew they received psilocybin and there was no comparison group, so larger controlled trials are needed to confirm the findings.

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.

Topics

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Adverse effect Alternative medicine Antidepressant Anxiety Clinical endpoint Clinical Global Impression Clinical trial Cognition Hallucinogen Internal medicine Major depressive episode Medicine Paroxetine Pathology Placebo Psilocybin Psychiatry Psychology Serotonin reuptake inhibitor Tolerability Treatment-resistant depression

Substances

Psilocybin

Conditions & symptoms

Anxiety Depression Sadness or low mood