SuicidalityMajor Depressive Disorder (MDD)Depressive DisordersPalliative & End-of-Life DistressAnxiety Disorders

Decreases in Suicidality Following Psychedelic Therapy: A Meta-Analysis of Individual Patient Data Across Clinical Trials

This meta-analysis (2022) assessed patient-level data on the effects of psychedelics on suicidality across seven clinical trials. It was found that, relative to baseline, psychedelic therapy was associated with large effect sizes and sustained decreases in suicidality. The effect size was medium at 6 months was significant at all time points except 7-8 weeks.

Authors

  • Richard Zeifman
  • Sandeep Nayak
  • Cory Ross Weissman

Published

Journal of Clinical Psychiatry
meta Study

Abstract

Objective

Suicide is a global health concern, and innovative interventions that target suicidality are needed. While psychedelic therapy shows promise for a range of mental health concerns, including suicidality, not all psychedelic therapy trials have published their suicidality results and no meta-analysis has been published on the topic. Therefore, we completed the first meta-analysis of patient-level data on the effects of psychedelics on suicidality.

Data Sources

We conducted a systematic search of MEDLINE, PsycINFO, and PubMed for all psychedelic therapy clinical trials (last search: November 5, 2020).

Study Selection

We identified all psychedelic therapy trials that included a measure or measure-item that assesses suicidality.

Data Extraction

Suicidality data were requested from study authors and extracted using a data extraction form developed for this study.

Results

We identified 8, and successfully collected data from 7, relevant trials. Analysis of standardized mean differences (SMDs) indicated that, relative to baseline, psychedelic therapy was associated with large effect sizes for acute (80-240 min) and sustained (1 day, 1-8 weeks, and 3-4 months) decreases in suicidality (SMD range = −1.48 to −2.36; 95% CI range, −4.30 to 0.23). At 6 months, the effect size was medium (SMD = −0.65; 95% CI, −1.14 to −0.16). Reductions in suicidality were significant at all time points except for 7-8 weeks. Acute and post-acute elevations in suicidality were rare (6.5% and 3.0%, respectively).

Conclusions

Limitations include heterogeneous samples and interventions, as well as limited sample size and the number of studies. Results provide preliminary support for the safety of psychedelic therapy and its positive effect on suicidality. Controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality may be warranted.

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Research Summary of 'Decreases in Suicidality Following Psychedelic Therapy: A Meta-Analysis of Individual Patient Data Across Clinical Trials'

Introduction

Suicide is a major global health problem, with roughly 800,000 deaths annually and substantially higher prevalence of suicidal thoughts and behaviours. Suicidality (including ideation, planning, and attempts) occurs across diagnostic categories, is common in major depressive disorder but also in contexts such as life-threatening illness, and predicts completed suicide. Existing interventions that reduce suicidality—such as cognitive–behavioural therapy, electroconvulsive therapy, selective serotonin reuptake inhibitors, and intravenous ketamine—have important limitations: modest or delayed effects in some cases, restricted accessibility or tolerability, brief duration of benefit (eg, ketamine commonly shows effects that wane within days), or safety concerns with repeated administration. These gaps have motivated interest in novel treatments that might rapidly and durably reduce suicidality. Weissman and colleagues set out to address the absence of a patient-level meta-analysis on psychedelic therapy and suicidality. Specifically, the investigators identified clinical trials that administered classic psychedelics (eg, psilocybin, ayahuasca, DMT, LSD, mescaline, peyote) and included a suicidality measure or suicidality item, requested participant-level suicidality data from study teams, and tested the hypothesis that psychedelic therapy would be associated with significant acute and sustained reductions in suicidality across trials. This approach aimed both to synthesise unpublished suicidality data and to examine safety signals such as acute or post-acute elevations in suicidality.

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Study Details

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