A randomized controlled trial of intranasal ketamine in migraine with prolonged aura

Objective: The aim of our study was to test the hypothesis that ketamine would affect aura in a randomized controlled double-blind trial, and thus to provide direct evidence for the role of glutamatergic transmission in human aura. Methods: We performed a double-blinded, randomized parallel-group controlled study investigating the effect of 25 mg intranasal ketamine on migraine with prolonged aura in 30 migraineurs using 2 mg intranasal midazolam as an active control. Each subject recorded data from 3 episodes of migraine. Results: Eighteen subjects completed the study. Ketamine reduced the severity ( p = 0.032) but not duration of aura in this group, whereas midazolam had no effect. Conclusions: These data provide translational evidence for the potential importance of glutamatergic mechanisms in migraine aura and offer a pharmacologic parallel between animal experimental work on cortical spreading depression and the clinical problem. Classification of evidence: This study provides Class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.