Intramuscular ketamine vs. midazolam for rapid risk-reduction in suicidal, depressed emergency patients: Clinical trial design and rationale.

Emergency department (ED) visits for suicidal ideation or behavior have been increasing in all age groups, particularly younger adults. A rapid-acting treatment to reduce suicidal thinking, adapted for ED use, is needed. Previous studies have shown a single dose of ketamine can improve depression and suicidal ideation within hours. However, most studies used 40 min intravenous infusions which can be impractical in a psychiatric ED. The ER-Ketamine study we describe here is a randomized midazolam-controlled clinical trial (RCT; NCT04640636) testing intramuscular (IM) ketamine's feasibility, safety, and effectiveness to rapidly reduce suicidal ideation and depression in a psychiatric ED. A pre-injection phase involves screening, informed consent, eligibility confirmation, and baseline assessment of suicidal ideation, depression, and comorbidities. The randomized double-blind IM injection is administered in the ED under research staff supervision, vital sign monitoring, pharmacokinetic blood sampling, and clinical assessments. The post-injection phase occurs on a psychiatric inpatient unit with follow-up research assessments through four weeks post-discharge. Outcome measures are feasibility, safety, and effects on suicidal ideation and depression at 24 h post-injection, and through follow-up. The target sample is