J Emerg Med. 2019 Apr;56(4):455-456

# THINK of Ketamine for Headache.

Goodnough R

QUOTE:"The THINK (Treatment of Headache with Intranasal Ketamine) trial is a timely addition to the literature (9). Benish et al. report a well-designed, prospective, single-blind trial comparing 1–2 doses of intranasal ketamine (0.75 mg/kg, with the option for 0.25 mg/kg 30 min later) to i.v. metoclopramide (10 mg) and diphenhydramine (25 mg) (9). Providers could opt to administer i.v. ketorolac (30 mg) or dexamethasone (10 mg) in the control arm (9). Ketamine displayed a clinically significant decrease in pain at 30 min (mean change in VAS 29.0 mm), though it was not superior to the control arm (mean change in VAS 22.2 mm) (9). A decrease in 13–18 mm has been described as clinically significant (1,3). The intervention and control arm showed similar rates of adverse effects (65.4 and 66.7%, respectively); though there was a higher incidence of mood changes and feelings of unreality in the ketamine group, the study was not powered to detect these differences (9). The majority (80%) of the control arm additionallyreceived i.v. ketorolac, which implies a similar effectiveness of intranasal ketamine to the combined administration of i.v. diphenhydramine, metoclopramide, and NSAID therapy at 30 min (9). The disparate outcomes demonstrated by previously published literature on ketaminein management of primary headache compared to the THINK trial may be reflective of variations in ketamine dosing, routes, or rate of infusion, or by the selection of metoclopramiderather than other dopamine antagonists. Amidst the current opioid epidemic, comfort withketamine as a viable intervention for pain relief adds to the emergency medicine provider’s armamentarium of nonopioid analgesics and, therefore, the investigation of ketamine to manage pain from primary headache is appealing. Further, the intranasal route of administration may limit the need for placement of i.v. lines or administration of multiple parenteral medicationsin this population."