INTERIM DATA FROM A RANDOMIZED PLACEBO-CONTROLLED TRIAL OF ACCELERATED TRANSCRANIAL MAGNETIC INTERMITTENT THETA-BURST STIMULATION AND ADJUNCTIVE D-CYCLOSERINE FOR SUICIDAL IDEATION

Background

Suicide is a major public health problem and one of the most tragic outcomes in psychiatry. Individuals with a history of suicidal behavior are at elevated risk for reattempting suicide. Our preliminary data suggests that pharmacologically enhancing transcranial magnetic intermittent theta-burst stimulation (iTBS) with the partial NMDA receptor agonist, D-Cycloserine, leads to rapid resolution of suicidal ideation and reductions in implicit suicide risk as measured by the Death/Suicide Implicit Association Test. Here, among individuals with a past history of suicidal behavior and a recurrence of suicidal ideation, we test the anti-suicidal effects of D-Cycloserine pharmacological enhancement of twice-daily iTBS.

Methods

A sample of n=54 adults are planned for this 2-week, single-site, randomized placebo-controlled trial. Eligibility is based previous at least one previous suicide attempt based on the Columbia Suicide Severity Rating Scale, current moderate severity depressive symptoms (HRDS-17  15), and current suicidal ideation (MADRS suicide item 10  4). Participants are randomized in a 1:1 ratio to daily placebo or D-Cycloserine (100mg) before receiving iTBS treatments. These consist of twice-daily iTBS separated by 60 minutes to the left dorsolateral prefrontal cortex using the BeamF3 method, for a total of 20 treatments over 10 days. The primary outcome is change in performance on the D/S-IAT from baseline to post-treatment. Secondary outcomes include change in suicidal ideation, change in depressive symptoms, and change in suicidal behaviors over a 6-month follow up period.

Results

Interim analyses with prespecified stopping and unblinding criteria are scheduled for n=39 of a planned sample of n=54 adults. Current enrollment stands at n=25.

Conclusion

This clinical trial tests the anti-suicidal efficacy of pharmacologically enhanced accelerated iTBS. Superiority of iTBS+D-Cycloserine over iTBS+Placebo would inform a novel treatment strategy for a population uniquely deserving of treatment options.

References

Cole J, Sohn MN, Harris AD, et al. Efficacy of adjunctive DCycloserine to intermittent theta-burst stimulation for major depressive disorder: a randomized clinical trial. JAMA Psychiatry 2022; 79:1153–1161 Sohn MN, Cole J, Bray S, and McGirr A. Intermittent theta-burst stimulation with adjunctive D-Cycloserine rapidly resolves suicidal ideation and decreases implicit association with death/suicide Psychol. Med. (2025), Article e13