This open-label, Phase II/III trial (n=36) will study the effects of ketamine (35mg/70kg via intravenous infusion) on suicidal ideation in individuals with major depressive disorder (MDD).
Conducted by The Royal’s Institute of Mental Health Research in Ottawa, Canada, this study aims to explore whether ketamine can rapidly reduce active suicidal thoughts and uncover the biological and psychological mechanisms underpinning these effects. Participants will receive four intravenous ketamine infusions, administered twice weekly over a two-week period. MRI scans will be performed before the first and after the final infusion to assess changes in brain structure and function, particularly in white matter microstructure and other neural markers like extracellular free water and neurite density index. Participants will also complete clinical assessments and qualitative interviews to explore changes in mood, suicidal ideation, and psychological distress.
The research seeks to provide insight into how ketamine produces its antisuicidal effects, with the hope of identifying new brain targets for suicide prevention. Individuals eligible for the study must be aged 18–65, have MDD with active suicidal ideation, and meet strict health and safety criteria. The findings could inform future therapeutic strategies and advance scientific understanding of suicide risk and its treatment.
Trial Details
The goal of this clinical trial is to treat active suicidal ideation in individuals with Major Depressive Disorder (MDD) using ketamine and to understand suicidal ideation by examining biological mechanisms using magnetic resonance imaging (MRI), and psychological mechanisms through validated clinical scales and qualitative interviews. The main questions it aims to answer are: 1. Will ketamine will reduce suicidal ideation in a significant proportion of study participants? 2.Will reduction in suicidal ideation will be accompanied by rapid changes in neuroimaging biomarkers? Participants will receive four intravenous (IV) ketamine infusions administered twice weekly for two weeks. Participants will undergo two identical MRI scans: 1) within 48 hours prior to starting ketamine treatment, and 2) 24 hours after the fourth ketamine infusion. Suicidal ideation and depressive symptoms will be assessed prior to each imaging session alongside additional self-report measures. Qualitative interviews will occur within 72 hours after the fourth ketamine treatment.Trial Number NCT06891300