Analysis Explores Ketamine Use for Treatment of Migraines, Primary Headaches


Research presented during the APhA 2021 Annual Meeting and Exposition examined the clinical use of ketamine as an abortive therapy for migraines and primary headaches.


A new research review explores whether ketamine may be used as an effective abortive therapy option for migraine and primary headaches.

The findings were presented by Stephanie L. Gianturco, PharmD, postdoctoral fellow in medical and regulatory affairs at the University of Maryland School of Pharmacy during a poster presentation at the American Pharmacists Association (APhA) 2021 Annual Meeting and Exposition, which is being held virtually March 12-15, 2021.

“Migraine is ranked as the second-most disabling neurological condition in terms of years lost to disability,” study author Gianturco said in her presentation. Over 1.2 million patients visit emergency department (ED) annually and 15% of the population is afflicted by migraine. However, despite standard evidence-based treatments, clinical trials show that less than 25% of ED patients experience sustained relief after treatment of acute migraine.

A general anesthetic, ketamine has typically been used in the operating room. However, due to its analgesic effects at sub-anesthetic levels, ketamine has also been used as an abortive therapy for migraine and primary headache.

For the review, investigators conducted a search of randomized and nonrandomized controlled trials (RCTs) that used ketamine for the treatment of migraine or primary headache. The search strategies used a combination of controlled vocabulary terms and key words to describe 2 concepts: ketamine, esketamine, or arketamine; and headache or migraine. 

Of the 1112 articles that were screened by reviewers, 5 were included after merging multiple reports of the same study. Two of the studies that met the inclusion criteria were ongoing and had not yet reported results.

The investigators looked at change in pain score as the primary outcome:

  • One study showed that intranasal ketamine reduced aura severity compared with intranasal midazolam. However, the study authors did not endorse widespread use of ketamine due to a limited study population with prolonged migraine aura.
  • One study reported that subcutaneous ketamine was more effective than normal saline in acute and chronic therapy.
  • Several studies did not show ketamine to be effective; however, they all recommended further investigation with ketamine via a different route of administration or dose and in larger populations.

Secondary outcomes looked at adverse events (AEs), patient satisfaction, and need for rescue analgesia:

  • Reported adverse effects of ketamine included fatigue, dizziness, feeling of unreality, generalized discomfort, nausea, and mood changes.
  • Patients were more likely to report satisfaction with prochlorperazine/diphenhydramine compared with ketamine.
  • Patients had similar rates of treatment satisfaction with ketamine versus metoclopramide/diphenhydramine or normal saline.
  • Ketamine-treated patients did not demonstrate a significant change in need for rescue analgesia compared with metoclopramide/diphenhydramine or prochlorperazine/diphenhydramine.

“In conclusion, further research is needed to determine whether ketamine should be used in migraine or primary headache treatments,” Gianturco said. Additional studies should also investigate appropriate dose and route of administration.

This research was supported by a Center of Excellence in Regulatory Science and Innovation grant to the University of Maryland from the FDA.


  1. Gianturco SL, Yoon S, Yuen MV, et al. A place for ketamine in the treatment of migraines and primary headaches. Presented at: American Pharmacists Association 2021 Annual Meeting & Exposition; virtual; March 12-15, 2021. Accessed March 12, 2021.
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