Psilocybin Improves Depression Symptoms in Treatment-Resistant Depression

A single 25 mg dose of COMP360 psilocybin, combined with psychological support, reduced symptoms of depression and was well tolerated by patients with treatment-resistant depression, according to research presented at Psych Congress 2022, held from September 17 to 20, 2022, in New Orleans, Louisiana.

As a combination of oral COMP360 treatment — a synthetic form of psilocybin — with psychological support, COMP360 psilocybin therapy is intended to treat adults with treatment-resistant depression. To further assess the efficacy and safety of COMP360 in adults in this depression subgroup, researchers looked at 2 clinical trials.

The first study, COMP001 (ClinicalTrials.gov Identifier: NCT03775200) a monotherapy double-blind controlled trial (N=233) of psilocybin therapy, used psilocybin therapy doses of 25/10/1 mg, respectively. The second study, COMP003 (ClinicalTrials.gov Identifier: NCT04739865) was an open-label trial (N=19) examining COMP360 (25 mg) psilocybin therapy with adjuvant therapy of serotonergic antidepressants. The primary outcome in both trials was change from baseline to week 3 in patients’ total score in the Montgomery-Asberg Depression Rating Scale (MADRS).

In COMP001 from day 2 through the end of week 3, the researchers found dose-dependent reductions in MADRS scores, with 25 mg COMP360 showing statistical superiority over 1 mg. The week 3 rates of response and remission were also better for COMP360 25 mg than for 1 mg, and they noted this sustained response through week 12. In COMP003, similar effects of COMP360 25 mg on MADRS scores and response/remission at week 3 were observed.

Researchers noted that COMP360 25 mg was well-tolerated, and more than 90% of treatment emergent adverse events were mild/moderate severity in both trials. A single dose of COMP360 25 mg with psychological support seemed to be well-tolerated and efficacious.

Among patients with treatment-resistant depression, “COMP360 (25 mg) psilocybin therapy reduced depression symptomatology at the primary endpoint (Week 3) and was well-tolerated,” the researchers stated. They added “Single administration of COMP360 25 mg psilocybin appears to be a rapid, efficacious, and well-tolerated monotherapy for adult participants with TRD [treatment-resistant depression].” They urge further safety and efficacy evaluation in large, controlled studies.

Disclosure: This research was supported by COMPASS Pathways, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.