The THINK (Treatment of Headache with Intranasal Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine with Intravenous Metoclopramide

Headache is a common chief complaint in the emergency department (ED) setting. To compare analgesia with metoclopramide and diphenhydramine vs. intranasal ketamine among ED patients with primary headache. We enrolled a convenience sample of adults with a primary headache in a randomized, single-blind, placebo-controlled trial. We randomized patients to either a control arm (intravenous metoclopramide and diphenhydramine) or intranasal ketamine. The primary outcome was change in pain 0–100 mm visual analog scale (VAS) score measured at study start and 30 min post completion of initial medication administration. Secondary outcomes included side effects, hospital admission, and return to care within 48–72 h. All 53 enrolled subjects completed the study, 26 of whom were allocated to the control arm and 27 to intranasal ketamine. The mean change in pain VAS score at 30 min post intervention was 22.2 mm in the control arm vs. 29.0 in the intranasal ketamine arm (effect size difference 6.8 mm, 95% confidence interval −5.8–19.4). The incidence of reported side effects was 65.4% in the control arm vs. 66.7% in the ketamine arm. Three patients (11.5%) allocated to the control arm required admission for headache pain control vs. 1 patient (3.7%) in the intranasal ketamine arm. Three (11.5%) additional patients in the control arm returned to the ED within 48–72 h for headache pain vs. none in the ketamine arm. In this small randomized study, intranasal ketamine was not superior to standard therapy among ED patients with primary headache syndromes.