Background. Suicidal ideation is a risk factor for suicidal behavior and a common symptom in patients with major depressive disorder (M.D.D). Suicidal thoughts often require rapid intervention(s) but very few antidepressant treatments are effective in reducing suicidal thoughts and until recently, none were fast-acting. Sub-anaesthetic dose ketamine has emerged as a novel, rapid-acting treatment that can reduce suicidal ideation within hours instead of weeks like other antidepressants. Aside from its therapeutic potential, the rapid effects of ketamine provide the opportunity to explore the biological and psychological underpinnings of suicidal ideation by examining patients over a short time frame before and after alleviation of suicidal ideation through treatment. The biological underpinnings of suicide are poorly understood but emerging evidence implicates the importance of brain white matter. The purpose of this study is to use ketamine to treat active suicidal thoughts in patients with depression and to harness ketamine’s rapid therapeutic effects to understand its biological underpinnings through advanced diffusion magnetic resonance imaging (MRI) – a technique that can reveal the microstructural properties of white matter.
Research Aims and Hypothesis - Aim 1: To measure changes in advanced diffusion MRI biomarkers (white matter microstructure, extracellular free water, neurite density index) pre-post repeated ketamine treatment in association with changes in suicidal ideation. Aim 2: To link changes in suicidal ideation pre-post ketamine treatment with changes in suicide-related psychological features including hopelessness, psychological pain, and perceived burdensomeness. Aim 3: To explore patient perceptions of change in suicidal ideation while undergoing ketamine treatment through qualitative interviews. The central hypothesis is that ketamine will reduce suicidal ideation in a significant proportion of study participants and that lessening of suicidal thoughts will be accompanied by rapid changes in diffusion MRI biomarkers.
Design and Methodology: In this prospective, longitudinal study, thirty-six patients with diagnosis of M.D.D referred for treatment of active suicidal ideation will undergo four twice-weekly administered intravenous ketamine infusions in our hospital-based ketamine clinic. Participants will undergo two identical MRI scans, 1) before treatment initiation, and 2) 24 hours after their fourth ketamine infusion. Changes in diffusion MRI biomarkers will be assessed alongside changes in suicidal ideation severity. After treatment, participants will share their perspectives on how their suicidal ideation changed.
Potential Impact: Higher risk groups, such as patients with active suicidal ideation treated in hospital settings, may provide a feasible model for examining how an individual progresses towards suicide. For study participants, ketamine may offer a rapid strategy to lessen their suicidal thoughts and provide a window of opportunity for them to engage in other, longer-term strategies to decrease their suicide risk. The ability to rapidly decrease suicide risk through treatment may be a transformative approach to advance our understanding of suicidal ideation. Harnessing the unique properties of ketamine combined with brain imaging may clarify the brain circuitry involved in suicidal thoughts and identify new potential targets for treatment and prevention.
