Phase II, randomised, quadruple-blind trial (n=110) comparing i-CBT plus six IV ketamine infusions versus i-CBT plus six IV midazolam infusions to reduce suicidality in treatment-resistant depression.
Background: Suicide is a leading cause of death among young people; novel scalable interventions are needed. i-CBT is accessible but not rapidly effective for suicidality, whereas IV ketamine produces rapid reductions in suicidal thoughts.
Design: A 13-week, multi-site randomized parallel-group trial; all participants receive weekly i-CBT for 13 weeks and are randomised to six IV ketamine infusions (flexible 0.5–0.85 mg/kg) or six IV midazolam infusions (0.02–0.035 mg/kg) over the first 30 days. Primary endpoint at day 30 with follow-up to day 91.
Internet CBT for 13 weeks plus six IV ketamine infusions over first 30 days (flexible dosing).
First two infusions 0.5 mg/kg over 40 min; infusions 3–4 flexible 0.5–0.75 mg/kg; infusions 5–6 flexible up to 0.85 mg/kg based on response.
Internet-based CBT modules ~45–50 min each with homework and therapist feedback.
Internet CBT for 13 weeks plus six IV midazolam infusions over first 30 days (active comparator).
Midazolam hydrochloride 0.02 mg/kg first two infusions; flexible 0.02–0.03 mg/kg for infusions 3–4 and up to 0.035 mg/kg for 5–6; infusion duration ~40 min.
Internet-based CBT modules ~45–50 min each with homework and therapist feedback.