Ketamine Versus Crisis Response Plan Versus Enhanced Treatment as Usual for Suicide: A Pragmatic Controlled Trial in Two Brazilian Cities

Abstract

Suicide is a major public health issue globally, with significant morbidity, mortality, and economic costs. Effective interventions are needed, especially for high-risk populations. Recent advances have highlighted the potential of pharmacological interventions like ketamine and psychotherapeutic approaches such as Crisis Response Planning (CRP) to rapidly reduce suicidal thoughts and behaviors. However, real-world and large-scale evaluations of these interventions are limited, particularly in diverse settings such as Brazil, where suicide rates have been rising. This study aims to compare the effectiveness of single-session ketamine infusion plus enhanced usual care (eTAU) against CRP plus eTAU against eTAU alone in reducing suicidal thoughts and behaviors among non-hospitalized, high-risk suicidal patients in Jaguariúna and Indaiatuba, Brazil. Secondary objectives include evaluating the impact on overall mental health status, assessing time to new suicidal crisis, analyzing treatment response based on demographic factors, and exploring cost-effectiveness. A randomized controlled trial will be conducted in two Brazilian cities with a total population of 310,000. Eligible participants are those presenting at emergency departments with high suicide risk, defined as recent suicide attempts or severe suicidal thoughts. Participants will be randomized into three groups: ketamine infusion plus eTAU, CRP plus eTAU, and eTAU alone. Outcomes will be measured using standardized psychopathological scales, sociodemographic data, and biological markers, with follow-up assessments at multiple time points up to 24 weeks post-intervention. Data will be analyzed using mixed-effects models for repeated measures, survival analysis, and Cox proportional hazards regression, among other methods. This study is expected to provide valuable insights into the effectiveness and feasibility of rapid interventions for suicide prevention in a real-world, public health setting, addressing an urgent global health concern.