Intranasal Ketamine Reduces Pain and Concomitant Drug Use for Refractory Headache

patient man with headache on the hospital bed
This study assessed the efficacy and safety of intranasal ketamine as an outpatient treatment for refractory headache.

The following article is part of conference coverage from the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the AAN 2021 Virtual Annual Meeting.

Individuals with refractory headache may benefit from treatment with intranasal ketamine spray. These findings from a single-center retrospective study will be presented during the American Academy of Neurology 2021 Virtual Annual Meeting, to be held April 17 to 22, 2021.

To assess the clinical efficacy and safety of the use of intranasal ketamine for the acute treatment of refractory headache beyond the inpatient setting, study researchers from Thomas Jefferson University conducted a telephone interview study. Patients (N=245) prescribed intranasal ketamine from January 2019 to February 2020 were identified by electronic medical records. A total of 168 of these patients participated in the telephone survey.

The patients had a mean age of 44.5 (±13.8) years and the majority (n=134) were women. The most frequently documented diagnosis was chronic migraine (83.9%; n=141) and most of the patients were currently using intranasal ketamine (63.7%; n=107).

The average usage of intranasal ketamine was 11.8 (±8.9) days per month. On each usage day, patients administered a mean of 7.9 (±6.9) sprays of ketamine. Average headache intensity was reported to be 7.6 (±1.7) on a 10-point scale prior to taking ketamine and 4.7 (±2.2) after administration (P <.01). Headache relief after spray occurred after an average of 74.1 minutes.

The patients indicated headache relief due to ketamine was successful 70.8% of the time and 71.4% (n=120) reported they used fewer additional acute medications for headache relief while using intranasal ketamine.

No adverse effects were reported by over a quarter of patients (26.2%; n=44). The other patients reported fatigue (20.8%), blurred vision or diplopia (20.8%), nausea (15.5%), vivid dreams (10.1%), hallucinations (7.7%), vomiting (3%), tremor (2.4%), extreme fear (1.8%), and myoclonus (1.2%).

The limitations of this study included its single-center, retrospective design and the fact that responses were self-reported.

The study authors concluded that intranasal ketamine spray had the potential to be an acute treatment among patients with refractory headache. Most patients who used this therapy reported headache relief and reduction of other pain medication use with little risk for serious adverse effects.


Park J, Natekar A, Young W, Viscusi E, Yuan H, Marmura M. Intranasal ketamine as a promising acute treatment for refractory headache. Presented at: American Academy of Neurology 2021 Virtual Annual Meeting; April 17-22, 2021. Abstract P10.015