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Ketamine for Refractory Headache: A Retrospective Analysis
  1. Eric S. Schwenk, MD*,
  2. Amir C. Dayan, MD*,
  3. Ashwin Rangavajjula, MD,
  4. Marc C. Torjman, PhD*,
  5. Mauricio G. Hernandez, BS*,
  6. Clinton G. Lauritsen, DO,
  7. Stephen D. Silberstein, MD,
  8. William Young, MD and
  9. Eugene R. Viscusi, MD*
  1. *From the Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University;
  2. Department of Anesthesiology, Thomas Jefferson University Hospital; and
  3. Department of Neurology, Thomas Jefferson University, Philadelphia, PA
  1. Address correspondence to: Eric S. Schwenk, MD, Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, Suite 8130, Gibbon Bldg, 111 South 11th St, Philadelphia, PA 19107 (e-mail: Eric.Schwenk{at}


Background and Objectives The burden of chronic headache disorders in the United States is substantial. Some patients are treatment refractory. Ketamine, an N-methyl-D-aspartate antagonist, provides potent analgesia in subanesthetic doses in chronic pain, and limited data suggest it may alleviate headache in some patients.

Methods We performed a retrospective study of 61 patients admitted over 3 years for 5 days of intravenous therapy that included continuous ketamine to determine responder rate and patient and ketamine infusion characteristics. Pain ratings at 2 follow-up visits were recorded. An immediate responder was a patient with decrease of 2 points or greater in the numerical rating scale (0–10) from start to final pain in the hospital. Sustained response at office visits 1 and 2 was determined based on maintaining the 2-point improvement at those visits. Patients were assessed daily for pain and adverse events (AEs).

Results Forty-eight (77%) of the 61 patients were immediate responders. There were no differences regarding demographics, opioid use, or fibromyalgia between immediate responders and nonresponders. Maximum improvement occurred 4.56 days (mean) into treatment. Sustained response occurred in 40% of patients at visit 1 (mean, 38.1 days) and 39% of patients at visit 2 (mean, 101.3 days). The mean maximum ketamine rate was 65.2 ± 2.8 mg/h (0.76 mg/kg per hour). Ketamine rates did not differ between groups. Adverse events occurred equally in responders and nonresponders and were mild.

Conclusions Ketamine was associated with short-term analgesia in many refractory headache patients with tolerable adverse events. A prospective study is warranted to confirm this and elucidate responder characteristics.

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  • E.S.S. has received consulting fees from Avenue Therapeutics. C.G.L. has received honoraria from Cefaly Technology. S.D.S. receives, or has received, honoraria from Alder Biopharmaceuticals; Allergan, Inc; Amgen; Avanir Pharmaceuticals, Inc; Curelator, Inc; Dr Reddy’s Laboratories; eNeura Inc; electroCore Medical, LLC; Lilly USA, LLC; Medscape, LLC; NINDS; Supernus Pharmaceuticals, Inc; Teva Pharmaceuticals; Theranica; and Trigemina, Inc. W.Y. has received consulting fees from Allergan; he is on the advisory board for Amgen, Avanir, Cipla, Alder, Eli Lilly, and Supernus. He has received research support from Allergan, Amgen, Autonomic Technologies, Colucis, Cumberland, Dr Reddy’s Laboratories, Eli Lilly, Novartis, PCORI, Scion, Teva, and Zosano. Eugene Viscusi has served as a consultant for AcelRx, Medicines Company, Mallinkrodt, Trevena, Cara Pharmaceuticals, Salix, AstraZeneca, and Merck. His institution has received research grants in the past from AcelRx, Adolor, Progenics, and Pacira. He has been a paid lecturer for AcelRx, Merck, Salix, and Mallinkrodt. None of these companies were involved in any aspect of the development of this manuscript. A.C.D., A.R., M.C.T., and M.G.H. declare no conflict of interest.

  • Institutional affiliation of manuscript: Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.

  • Source of funding: Departmental funding.

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