Intravenous Ketamine for Depressed and Suicidal Adolescents in the Emergency Department: A Randomized Double-Blind...

Adolescents frequently seek care in the emergency department (ED) for behavioral health emergencies. Due to national shortages in staffing, limited opportunities to begin treatment on site in most centers and, thus, the frequent default to elusive inpatient psychiatric beds as a means of stabilization, adolescents may spend prolonged amounts of time boarding in the ED, often without treatment. Ketamine is a rapid-acting antidepressant with emerging evidence in adults, but data are limited on its effectiveness in suicidal youth. We aimed to evaluate the effectiveness of a single dose of intravenous (IV) ketamine on depression and suicidality scores compared to placebo in adolescents with treatment-resistant depression presenting to the ED with suicidal ideation.

We conducted a two-arm randomized double-blind placebo controlled trial on a convenience sample of adolescents 12-17 years of age with treatment-resistant depression (trialed at least two antidepressants for at least four weeks each) who presented to the ED with suicidal ideation requiring psychiatric admission. Exclusion criteria included psychosis, substance abuse disorder, intoxication, developmental delay, aggressive behavior, and medical contraindications to ketamine. Subjects were randomized to receive a single dose of ketamine (0.2 mg/kg IV, maximum 35 mg) or saline placebo over two minutes. They completed the Beck Youth Inventory (BYI) and Suicidal Ideation Questionnaire (SIQ) at baseline and at 1 hour, 3 hours, 1 day, 3 days, and 7 days post-treatment. We compared groups with the Fisher exact and two-sided rank-sum tests. Our primary outcome measure was the proportion of subjects with a reduction of ≥ 50% on the BYI and SIQ within 3 hours after treatment.

The 29 subjects (14 placebo, 15 ketamine) did not differ significantly in demographic and clinical characteristics. Despite reductions in BYI and SIQ in both groups, the proportions achieving ≥ 50% reductions did not differ significantly at 1 hour (SIQ: placebo, 0% vs ketamine 14.3 % [P = .48]; BYI Anxiety Inventory: placebo, 0% vs ketamine 21.4% [P = .22]; BYI Depression Inventory: placebo, 0% vs ketamine 15.4% [P = .22]). Differences at 3 hours were less pronounced. Adverse effects were more frequent in the ketamine group, most notably signs of dissociation (7% vs 60%, P = .004), with none after the 1-hour observation period.

The ED offers an opportunity to deliver rapid-acting antidepressant treatment for suicidal adolescents. Although low-dose ketamine was not associated with greater reductions in depression or suicidality than placebo, this study demonstrated feasibility and highlights the need for larger studies to determine optimal ketamine dosing, route of administration, and implementation strategies in the ED setting.