Low-dose Ketamine Does Not Improve Migraine in the Emergency Department: A Randomized Placebo-controlled Trial

Introduction: Patients frequently present to the emergency department (ED) with migraine headaches. Although low-dose ketamine demonstrates analgesic efficacy for acute pain complaints in the ED, headaches have historically been excluded from these trials. This study evaluates the efficacy and safety of low-dose ketamine for treatment of acute migraine in the ED.

Methods: This randomized, double-blinded, placebo-controlled trial evaluated adults 18 to 65 years of age with acute migraine at a single academic ED. Subjects were randomized to receive 0.2 milligrams per kilogram of intravenous (IV) ketamine or an equivalent volume of normal saline. Numeric Rating Scale (NRS-11) pain scores, categorical pain scores, functional disability scores, side effects, and adverse events were assessed at baseline (T0) and 30 minutes post-treatment (T30). The primary outcome was between-group difference in NRS score reduction at 30 minutes.

Results: We enrolled 34 subjects (ketamine=16, placebo=18). Demographics were similar between treatment groups. There was no statistically significant difference in NRS score reductions between ketamine and placebo-treated groups after 30 minutes. Median NRS score reductions at 30 minutes were 1.0 (interquartile range [IQR] 0 to 2.25) for the ketamine group and 2.0 (IQR 0 to 3.75) for the placebo group. Between-group median difference at 30 minutes was -1.0 (IQR -2 to 1, p=0.5035). No significant differences between treatment groups occurred in categorical pain scores, functional disability scores, rescue medication request rate, and treatment satisfaction. Side Effect Rating Scale for Dissociative Anesthetics scores in the ketamine group were significantly greater for generalized discomfort at 30 minutes (p=0.008) and fatigue at 60 minutes (p=0.0216). No serious adverse events occurred in this study.

Conclusion: We found that 0.2mg/kg IV ketamine did not produce a greater reduction in NRS score compared to placebo for treatment of acute migraine in the ED. Generalized discomfort at 30 minutes was significantly greater in the ketamine group. Overall, ketamine was well tolerated by migraine-suffering subjects. To optimize low-dose ketamine as an acute migraine treatment, future studies should investigate more effective dosing and routes of administration.