Article Summary
Clinical Summary: Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Trial
Patients with chronic suicidal ideation often remain symptomatic despite multiple adequate antidepressant trials, and most psychedelic studies have excluded them entirely. This study addresses whether a single psilocybin session with psychological support can produce rapid antisuicidal benefit in a population with persistent, treatment-resistant suicidal thoughts.
Design
This 12-week, open-label, single-arm, naturalistic trial evaluated a single 25-mg dose of COMP360, a proprietary pharmaceutical-grade synthetic psilocybin formulation (COMPASS Pathways), in 20 adults with chronic SI.
N
20
Population
20 adults with chronic SI
Duration
12-week
Key Findings
- At the week 3 primary end point, the mean reduction in Modified Scale for Suicidal Ideation score was 13.95 points, with a large within-subject effect size (Cohen d = 1.73).
- By week 3, 15 of 20 participants (75%) achieved an antisuicidal response (≥50% reduction from baseline MSSI), and 9 participants (45%) achieved full remission of SI (MSSI = 0).
- At week 12, 7 of 20 participants (35%) had remission of SI (MSSI=0), and an additional 7 participants (35%) had minimal residual ideation (MSSI score of 1 or 2).
- Changes in suicidal ideation and depressive symptoms were strongly linked, with baseline-to-week 3 change scores on the MSSI and MADRS strongly correlated (r = 0.70, P < .001).
- Safety was generally favorable, with no serious AEs and no discontinuations due to an AE, but 2 of 20 participants (10%) experienced an increase in MSSI score relative to their baseline value, including 1 participant whose score rose from 17 at baseline to 23 at week 12.
Clinical Bottom Line
A single 25-mg psilocybin dose given with structured psychological support produced large, rapid reductions in chronic suicidal ideation that were sustained through 12 weeks in this open-label cohort. The signal is clinically compelling, but ongoing safety monitoring remains essential because worsening suicidal ideation occurred in 2 of 20 participants.
Practice Implications
- For patients with chronic SI despite at least 2 adequate antidepressant trials, psilocybin-assisted therapy is a potential emerging option for rapid symptom reduction, but current evidence remains limited to an open-label pilot.
- Monitor suicidal ideation directly after treatment rather than inferring benefit from mood improvement alone, since MSSI and MADRS changes were correlated (r = 0.70, P < .001) but not identical outcomes.
- Plan close follow-up beyond the acute response window: mean MSSI was lowest at week 1 (3.4) and then rose to 4.6 at week 3 and 5.5 at week 12, suggesting some symptom return over time.
- Maintain careful screening and postsession monitoring, especially in patients with high anxiety or trauma-related symptoms, because 1 participant required lorazepam on the dosing day and 2 of 20 participants (10%) had increased MSSI relative to baseline.
