Psilocybin may offer a treatment option for major depressive disorder (MDD) as it proved effective in reducing depressive and anxiety symptoms, according to a systematic review of randomized controlled trials (RCTs) published in Frontiers in Psychiatry.

Previous research has explored novel treatments for MDD, such as ketamine and esketamine. This review sought to assess the effectiveness, safety, and tolerability of psilocybin as an adjunctive treatment in physically healthy adults with MDD.

Researchers conducted a systematic review of six online databases (PubMed, Cochrane Library, PsycINFO, EMBASE, Chinese Journal Net, and WanFang) according to PRISMA guidelines.

Inclusion criteria was defined as follows: the participants were physically healthy patients aged 18 and older and diagnosed with MDD according to diagnostic criteria; the RCT studied an adjunctive psilocybin intervention compared to a control group; primary outcomes were changes in depressive symptoms according to standardized scales; and the study design of the RCT focused on efficacy, safety, and tolerability of adjunctive psilocybin.

Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD.

In total, the researchers assessed 5 RCTs involving 472 adult patients with MDD. The mean age across study samples ranged 36.8 to 41.2 and 48.4% of patients were men. Among the 472 patients, 274 received psilocybin while 198 served as control individuals.

Out of the 5 RCTs, 2 revealed inconclusive findings on the effects of psilocybin. However, the remaining 3 RCTs indicated a positive impact on depressive symptoms.

Psilocybin also showed significant anxiolytic effects in 4 of the RCTs. Additionally, the researchers identified only 1 study in which psilocybin was more effective in reducing symptoms of suicidal ideation. Overall, the discontinuation rates were comparable between psilocybin and control groups, and the most common adverse reactions reported were mild to moderate cases of headache.

“Studies should focus on determining the optimal dose of psilocybin to reduce depression scores while minimizing side effects,” the researchers noted.

Study limitations included a small sample size, lack of meta-analysis due to heterogeneity, difficulty isolating psilocybin’s effects, and limited generalizability to non-adult age groups.

This article originally appeared on Psychiatry Advisor

References:

 Li L, Mo Y, Shi Z, et al. Psilocybin for major depressive disorder: a systematic review of randomized controlled studies. Front Psychiatry. 2024;15. doi:10.3389/fpsyt.2024.1416420.