Effect of psilocybin therapy on suicidal ideation, attempts, and deaths in people with psychiatric diagnoses: a systematic review and meta-analysis

Background: Suicidal ideation, attempts, and deaths present a major and tragic public health concern. Recent trials of psilocybin therapy (PT) have shown promise in treating treatment-resistant depression and have found a reduction in suicidal ideation. Given the growth of PT research, there is a need to further understand its effect on suicidal ideation, attempts, and deaths.

Objective: To assess and synthesize evidence on the effects of PT on suicidal ideation, attempts, and deaths in psychiatric patients.

Design: PRISMA-compliant systematic review and meta-analysis. Data source: MEDLINE, EMBASE, Cochrane, and PsychINFO.

Method: Databases were searched for randomized controlled trials of PT in adults with psychiatric diagnoses that reported suicide outcomes (ideation, attempts, and deaths). Abstract and full-text screening were conducted, and suicide outcomes were extracted. Meta-analysis was performed with a random effects model to assess changes in suicide outcomes compared to control through the standardized mean difference (SMD). Assessment of heterogeneity, risk of bias, and subgroup analysis was completed.

Results: Nine studies were included ( N = 593; 335 psilocybin & 258 control). Two studies were excluded from meta-analysis because suicide-related outcomes data were not available. Participants with PT experienced a small and significant decrease in suicidal ideation compared to control ( k = 7, SMD = −0.24, 95% CI −0.42 to −0.06, p = 0.008, I 2 = 0%). There was no publication bias found. Subgroup analysis found no significant differences between groups. No study reported suicide attempts or suicide deaths. Two studies had a high risk of bias.

Conclusion: Psilocybin therapy may reduce suicidal ideation in adults with psychiatric diagnoses. Current studies are limited by small sample size, lack of follow-up data, and assessment of blinding.

Trial Registration: CRD42023445706.