iTBS+D-Cycloserine for Youth Suicide

Methods: 54 participants between 18-24 years old with clinically significant past week suicidal ideation, defined as a score ≥4 on item 10 of the Montgomery Asberg Depression Rating Scale (MADRS), at least moderate depressive symptoms (≥15 Hamilton Depression Rating Scale-17 \[HAMD-17\]), and a history of at least one suicide attempt will be recruited. It is important to note that suicidal ideation occurs on a spectrum and that scores on the MADRS item 10 range from 0-6. A score of 4 = "Probably better off dead. Suicidal thoughts are common, and suicide is considered as a possible solution, but without specific plans or intention." A score of 6 = "Explicit plans for suicide when there is an opportunity. Active preparations for suicide." Within this range, an individual may have active or passive suicidal ideation with or without intent or a plan. Individuals with active suicidal ideation, intent, or plan will be eligible to participate in the study if they are currently admitted as an inpatient. Participants will complete a screening visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible subjects will be randomized in a 1:1 ratio to receive either accelerated iTBS+placebo or accelerated iTBS+D-Cycloserine. The randomization sequence will be generated with random number generation, a block size of 6, and allocation concealment. Double-blind assignment and allocation concealment will be maintained by sequential numbering. Patients will be randomly assigned to receive either accelerated iTBS+D-Cycloserine or accelerated iTBS+placebo treatments. Patients without blood work within the past month will have laboratory tests done to rule out hematological, hepatic, and renal disease. The primary outcome of interest is change in performance on the Death/Suicide-IAT from baseline to treatment end. Performance on this measure and other cognitive tasks will also be assessed at 1-month and 6-month follow-ups. Clinical outcomes will be quantified using change on the clinician-rated Scale for Suicidal Ideation (SSI) and MADRS and self-reported measures of depression and anxiety. These symptoms will be assessed at baseline, week-1 (halfway), week-2 (end of treatment), one month, and 6-months post-treatment. Change in suicidal behaviors over the 6-months prior and following treatment will also be assessed using the Columbia Suicide Severity Rating Scale (CSSRS) and medical record review.