OUTCOMES IN DEPRESSION SYMPTOMATOLOGY WITH HIGH AND LOW LEVELS OF SUICIDAL IDEATION

Psychedelic therapy demonstrates promising antidepressant effects in patients with difficult-to-treat depression. However, patients that experience suicidal ideation (SI) are frequently excluded from clinical trials due to safety concerns. Excluding patients with high SI limits the generalizability of findings and access to potentially effective treatments. We examined whether the presence of high SI predicts treatment response to psilocybin therapy, as well as whether the change in SI from pre-to post-treatment predicted depressive outcomes.

Methods

45 patients across three difficult-to-treat depression studies by Aaronson et. al, received a single 25mg dose of COMP360 alongside therapeutic support. The MontgomeryÅsberg Depression Rating Scale (MADRS) was used to assess depressive symptom severity at baseline and 12 weeks post-treatment. The Columbia-Suicide Severity Rating Scale (CSSRS) was used to assess SI at baseline and immediately following treatment. Subjects were divided into two groups based on screening scores: high SI (C-SSRS > 2) and low SI (≤2 CSSRS). Paired one tailed t-tests were conducted to assess mean MADRS differences at baseline and Week 12. An analysis of covariance (ANCOVA) was conducted to examine whether MADRS Week 12 scores differed between SI groups after controlling for the severity of depression at baseline. An exploratory linear regression was conducted to assess whether the change in C-SSRS scores predicted MADRS outcomes at Week 12 across all patients.

Results

Patients in both groups experienced reductions in depressive symptoms (t(19) = 10.16, p < .001; t(24) = 10.67, p < .001) regardless of group assignment (t(38) = 1.51, p > .069). Controlling for baseline depression severity, no significant difference was found between high and low SI groups (F(1, 42) = 2.12, p = .153). The change in C-SSRS scores from baseline to immediately after treatment did not significantly predict depression outcomes at Week 12 (F(1, 42) = 0.01, p = .907).

Conclusions

Patients across three studies with varying degrees of SI experienced improvement to depression. These results exemplify that patients that experience high SI receive comparable benefit from psilocybin therapy as those with low SI. In addition, the change in SI from pre-to post-treatment did not predict long-term depressive outcomes. Despite historical exclusion, depressed patients with higher levels of SI may be a target for psilocybin treatment. Future research should examine the safety and efficacy of psychedelic therapy in populations with higher suicidal ideation.