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Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis
  1. Hsiangkuo Yuan1,
  2. Aniket Natekar2,
  3. Jade Park3,
  4. Clinton G Lauritsen1,
  5. Eugene R Viscusi1 and
  6. Michael J Marmura1
  1. 1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  2. 2Neurology, OhioHealth, Columbus, Ohio, USA
  3. 3Department of Neurology, Rush University, Chicago, Illinois, USA
  1. Correspondence to Dr Michael J Marmura, Department of Neurology, Thomas Jefferson University, Philadelphia, USA; Michael.marmura{at}


Introduction Subanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care.

Methods A retrospective study was conducted at a single tertiary headache center to assess the clinical effectiveness and tolerability of intranasal ketamine in patients with refractory chronic migraine. Candidates who received intranasal ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured telephone interviews were conducted on obtaining informed consent.

Results Of 242 subjects screened, 169 (79.9% women) of median (IQR) age 44 (22) years were interviewed. They reported a median (IQR) of 30 (9) monthly headache days and tried 4 (1) classes of preventive medications. Overall, they used 6 (6) sprays per day, with a median (IQR) of spray use of 10 (11) days per month. Intranasal ketamine was reported as ‘very effective’ in 49.1% and the quality of life was considered ‘much better’ in 35.5%. At the time of the interview, 65.1% remained current intranasal ketamine users and 74.0% reported at least one adverse event.

Conclusion In this descriptive study, intranasal ketamine served as an acute treatment for refractory chronic migraine by reducing headache intensity and improving quality of life with relatively tolerable adverse events. Most patients found intranasal ketamine effective and continued to use it despite these adverse events. Given the potential for overuse, it should be reserved for those clearly in need of more effective rescue treatment with appropriate safety precautions. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of intranasal ketamine in patients with migraine.

  • Treatment Outcome
  • Pain Management
  • Ambulatory Care

Data availability statement

The deidentified data may be available upon reasonable request.

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Data availability statement

The deidentified data may be available upon reasonable request.

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  • HY and AN are joint first authors.

  • Contributors Conception and design: HY, MM, ERV. Acquisition of data: HY, JP, AN. Analysis and interpretation of data: HY, JP. Drafting the article: HY, AN, JP. Revision for intellectual content: HY, AN, JP, CGL, ERV, MM. Final approval of completed article and guarantor: MM.

  • Funding The study was funded by patient philanthropy, Miles for Migraine.

  • Competing interests Within the past 24 months, HY has received funding from NIH (R44NS115460), institutional support for serving as an investigator from Teva and Abbvie, and royalties from Cambridge University Press and MedLink. AN and JP have no conflicts of interest. CGL has received consulting fees from Impel. ERV has received consultation fees from Heron, Esteve/Kowa, and Salix. MM has received compensation for consultation from Alder/Lumbeck, Axsome, Supernus, Theranica, Upsher-Smith, and Satsuma. He has participated in speaker bureaus for Eli Lilly and Amgen/Novartis and has received institutional support for serving as principal investigator from Teva, GammaCore, and Allergan/AbbVie. He has received payments for authorship or royalties from Demos Medical, Cambridge University Press, and MedLink.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.