Designing Clinical Trials to Assess the Impact of Pharmacological Treatment for Suicidal Ideation/Behavior: Issues and Potential Solutions

Suicide is a serious and growing public health concern yet randomized controlled trials (RCTs) that inform pharmacologic treatment remain limited. We emphasize the overall need for such trials and review the literature to highlight examples of trials that have aimed to study patients at elevated risk of suicide. We discuss key examples of existing psychotropic medication trials as well as psychotherapy intervention studies that can yield important design insights. Medications that have been studied in individuals at risk for suicide include lithium, clozapine, zolpidem, prazosin, ketamine, esketamine, and aripiprazole. While important design challenges should be considered—RCTs to study suicide are feasible and much needed. Issues such as overall trial design, patient-selection criteria, and the scales/tools used to assess suicidality are discussed.