Ketamine treatment in youth for fast reduction of suicidality and engagement in psychotherapy: A randomized placebo-controlled trial protocol

Background: Suicide is a leading cause of death in young persons. While ketamine has demonstrated rapid anti- suicidal effects, its safety and efficacy in youth has not been fully investigated. The Collaborative Assessment and Management of Suicidality (CAMS), a suicide-focused treatment shown to decrease suicidal ideation and symptom distress, has never been studied in combination with ketamine. Objectives: This study investigates whether ketamine infusion, as compared to placebo, rapidly reduces severe suicidality in youth and young adults and enhances effectiveness of CAMS to decrease suicidality after acute treatment and at 3-month follow-up. We explore whether participants who receive ketamine, as compared to placebo, have decreased suicidality, suicide attempts, emergency department visits for suicidality, and psychiatric readmissions over 3-month follow-up. Methods: This randomized controlled trial is enrolling 140 participants (ages 14-30) hospitalized with severe suicidal ideation or after attempted suicide. While hospitalized, participants are randomized to receive up to 6 treatments of either ketamine or placebo. Concurrently, participants engage in CAMS sessions, starting while inpatient and continuing post-discharge for up to 12 sessions via telehealth or until resolution of suicidality criteria are met. Monthly follow-up assessments are conducted for 3 months. Discussion: Historically, hospital admissions have not decreased suicidal behavior following discharge. We hypothesize that ketamine, as compared to placebo, will lead to rapid improvement in suicidality and enhance engagement in CAMS, requiring significantly fewer sessions to resolve high-risk suicidality after discharge. We hypothesize that the ketamine group will have decreased suicidality, suicide attempts, and readmissions compared to the placebo group over 3-month follow-up.