Current Pain and Headache Reports

, Volume 8, Issue 1, pp 19–26 | Cite as

Indomethacin-responsive headache syndromes

  • David W. Dodick


Indomethacin-responsive headache syndromes represent a unique group of primary headache disorders characterized by a prompt and often complete response to indomethacin to the exclusion of other nonsteroidal anti-inflammatory drugs and medications usually effective in treating other primary headache disorders. Because these headache disorders can easily be overlooked in clinical practice, they likely are more common than previously recognized. Indomethacin-responsive headache syndromes can be divided into several distinct categories: a select group of trigeminal-autonomic cephalgias, valsalva-induced headaches, and primary stabbing headache (ice-pick headache or jabs and jolts syndrome). Each category can be differentiated clinically and by the extent to which the individual headache disorders respond to indomethacin. The paroxysmal and continuous hemicranias invariably respond in an absolute manner to indomethacin, whereas valsalvainduced and ice-pick headaches may respond in an equally dramatic, but somewhat less consistent fashion. Hypnic headache recently has been described as another primary headache disorder that may respond to indomethacin.


Indomethacin Cluster Headache Primary Headache Disorder Paroxysmal Hemicrania Hemicrania Continuum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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References and Recommended Reading

  1. 1.
    Goadsby PJ, Lipton RB: A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic features, including new cases. Brain 1997, 120:193–209.PubMedCrossRefGoogle Scholar
  2. 2.
    Goadsby PJ, Edvinsson L: The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993, 33:48–56.PubMedCrossRefGoogle Scholar
  3. 3.
    Goadsby PJ, Edvinsson L: Human in vivo evidence for trigeminovascular activation in cluster headache: neuropeptide changes and effects of acute attacks therapies. Brain 1994, 117:427–434.PubMedCrossRefGoogle Scholar
  4. 4.
    Goadsby PJ, Edvinsson L: Neuropeptide changes in a case of chronic paroxysmal hemicrania: evidence for trigeminoparasympathetic activation. Cephalalgia 1996, 16:448–450.PubMedCrossRefGoogle Scholar
  5. 5.
    May A, Bahra A, Buchel C, et al.: Hypothalamic activation in cluster headache attacks. Lancet 1998, 352:275–278.PubMedCrossRefGoogle Scholar
  6. 6.
    May A, Bahra A, Buchel C, et al.: Functional magnetic resonance imaging in spontaneous attacks of SUNCT: shortlasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 1999, 46:787–790.CrossRefGoogle Scholar
  7. 7.
    Pascual J, Iglesias F, Oterino A, et al.: Cough, exertional, and sexual headaches: an analysis of 72 benign and symptomatic cases. Neurology 1996, 46:1520–1524.PubMedGoogle Scholar
  8. 8.
    Raskin NH: The cough headache syndrome: treatment. Neurology 1995, 45:1784.PubMedGoogle Scholar
  9. 9.
    Antonacci F, Sjaastad O: Chronic paroxysmal hemicrania (CPH): a review of the clinical manifestations. Headache 1989, 29:648–656.CrossRefGoogle Scholar
  10. 10.
    Boes C, Dodick DW: The clinical spectrum of chronic paroxysmal hemicrania seen at the Mayo Clinic from 1976–1996. Headache 2003, in press.Google Scholar
  11. 11.
    Russell D: Chronic paroxysmal hemicrania: severity, duration, and time of occurrence of attacks. Cephalalgia 1984, 4:53–56.PubMedCrossRefGoogle Scholar
  12. 12.
    Manzoni GC, Terzano MG, Bono G, et al.: Cluster headache: clinical findings in 180 patients. Cephalalgia 1983, 3:21–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Newman LC, Lipton RB, Soloman S: Hemicrania continua: ten new cases and a review of the literature. Neurology 1994, 44:2111–2114.PubMedGoogle Scholar
  14. 14.
    Peres MF, Silberstein SD, Nahmias S, et al.: Hemicrania continua is not that rare: 26 new cases. Neurology 2001 7:948–951. Very informative.Google Scholar
  15. 15.
    Perez MF, Siow HC, Rozen TD: Hemicrania continua with aura. Neurology 2001, 56(suppl 3):A452.Google Scholar
  16. 16.
    Bordini C, Antonaci F, Stovner LJ, et al.: Hemicrania continua: a clinical review. Headache 1991, 31:20–26.PubMedCrossRefGoogle Scholar
  17. 17.
    Rooke ED: Benign exertional headache. Med Clin North Am 1968, 52:801–808.PubMedGoogle Scholar
  18. 18.
    Rasmussen BK, Jensen R, Schroll M, et al.: Epidemiology of headache in a general population: a prevalence study. J Clin Epidemiol 1991, 44:1147–1157.PubMedCrossRefGoogle Scholar
  19. 19.
    Headache Classification Committee of the International Headache Society: Classification and Diagnostic Criteria for headache disorders, cranial neuralgias, and facial pain. Cephalalgia 1988, 8:1–96.Google Scholar
  20. 20.
    Pareja JA, Ruiz J, de Isla C, et al.: Idiopathic stabbing headache. Cephalalgia 1996, 16:93–96.PubMedCrossRefGoogle Scholar
  21. 21.
    Raskin NL: The hypnic headache syndrome. Headache 1988, 28:534–536.PubMedCrossRefGoogle Scholar
  22. 22.
    Dodick DW, Mosek A, Campbell JK: The hypnic (“alarm clock”) headache syndrome. Cephalalgia 1998, 18:152–156.PubMedCrossRefGoogle Scholar
  23. 23.
    Dodick DW: Hypnic headache: another indomethacinresponsive headache syndrome? Headache 2000, 40:830–835.PubMedCrossRefGoogle Scholar
  24. 24.
    Pareja JA, Sjaastad O: SUNCT syndrome: a clinical review. Headache 1997, 37:195–202.PubMedCrossRefGoogle Scholar
  25. 25.
    D’Andrea G, Granella F, Cadaldini M: Possible usefulness of lamotrigine in the treatment of SUNCT syndrome. Neurology 1999, 53:1609.PubMedGoogle Scholar
  26. 26.
    Graff-Radford SB: SUNCT syndrome responsive to gabapentin (Neurontin). Cephalalgia 2000, 20:515–517.PubMedCrossRefGoogle Scholar
  27. 27.
    Pareja JA, Sjaastad O: Chronic paroxysmal hemicrania and hemicrania continua: interval between indomethacin administration and response. Headache 1996, 36:20–23.PubMedCrossRefGoogle Scholar
  28. 28.
    Sanchez del Rio M, Caminero AB, Pascual J, et al.: Dose and efficacy of long-term indomethacin treatment of chronic paroxysmal hemicrania and hemicrania continua. Cephalalgia 2001, 21:507. Important study.Google Scholar
  29. 29.
    Kuritzky A: Indomethacin-resistant hemicrania continua. Cephalalgia 1992, 12:57–59.PubMedCrossRefGoogle Scholar
  30. 30.
    Sjaastad O, Stovner LJ, Stolt-Nielsen A, et al.: CPH and hemicrania continua: requirements of high indomethacin dosages. An ominous sign? Headache 1995, 35:363–367.PubMedCrossRefGoogle Scholar
  31. 31.
    Eross EJ, Swanson JW: Hemicrania continua: an indomethacin-responsive case with an underlying malignant etiology. Neurology 2001, 56(suppl 3):A452.Google Scholar
  32. 32.
    Antonaci F, Sjaastad O: Hemicrania continua: a possible symptomatic case, due to mesenchymal tumor. Funct Neurol 1992, 7:471–474.PubMedGoogle Scholar
  33. 33.
    Sjaastad O, Antonaci F: Chronic paroxysmal hemicrania and hemicrania continua: transition from one stage to another. Headache 1993, 33:551–554.PubMedCrossRefGoogle Scholar
  34. 34.
    Young WB, Silberstein SD: Hemicrania continua and symptomatic medication overuse. Headache 1993, 33:485–487.PubMedCrossRefGoogle Scholar
  35. 35.
    Newman LC, Lipton RB, Soloman S: Hemicrania continua: ten new cases and a review of the literature. Neurology 1994, 44:2111–2114.PubMedGoogle Scholar
  36. 36.
    Pascual J: Hemicrania continua. Neurology 1995, 45:2302–2303.PubMedGoogle Scholar
  37. 37.
    Bordini C, Antonaci F, Stovner LJ, et al.: Hemicrania continua: a clinical review. Headache 1991, 31:20–26.PubMedCrossRefGoogle Scholar
  38. 38.
    Wheeler SD: Lamotrigine efficacy in migraine prevention. Cephalalgia 2001, 21:368–383.CrossRefGoogle Scholar
  39. 39.
    Mariano HS, Alcantara MC, Bordini CA, Speciali JG: Relief of continuous hemicrania by gabapentin: a case report. Cephalalgia 2001, 21:504–509.CrossRefGoogle Scholar
  40. 40.
    Joubert J: Hemicrania Continua in a black patient: the importance of the non-continuous stage. Headache 1991, 31:482–484.CrossRefGoogle Scholar
  41. 41.
    Wheeler SD: Rofecoxib-responsive hemicrania continua. Headache 2000, 40:436–437.CrossRefGoogle Scholar
  42. 42.
    Trucco M, Antonaci F, Sandrini G: Hemicrania continua: a case responsive to piroxicam-beta-cyclodextrin. Headache 1992, 32:39–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Antonaci F, Sjaastad O: Chronic paroxysmal hemicrania (CPH): a review of the clinical manifestations. Headache 1989, 29:648–656.PubMedCrossRefGoogle Scholar
  44. 44.
    Coria F, Claveria LE, Jimenez-Jimenez FJ, de Seijas EV: Episodic paroxysmal hemicrania responsive to calcium channel blockers. J Neurol Neurosurg Psychiatry 1992, 55:166.PubMedGoogle Scholar
  45. 45.
    Shabbir N, McAbee G: Adolescent chronic paroxysmal hemicrania responsive to verapamil monotherapy. Headache 1994, 34:209–210.PubMedCrossRefGoogle Scholar
  46. 46.
    Hannerz J, Ericson K, Bergstrand G: Chronic paroxysmal hemicrania: orbital phlebography and steroid treatment. Headache 1987, 7:189–192.Google Scholar
  47. 47.
    Sjaastad O, Antonaci F: A Piroxicam derivative partially effective in chronic paroxysmal hemicrania and hemicrania continua. Headache 1995, 35:549–550.PubMedCrossRefGoogle Scholar
  48. 48.
    Warner JS, Wanul AW, McLean MJ: Acetazolamide for the treatment of chronic paroxysmal hemicrania. Headache 1994, 34:597–599.PubMedCrossRefGoogle Scholar
  49. 49.
    Harrigan MR, Tuteja S, Neudeck BL: Indomethacin in the management of elevated intracranial pressure: a review. J Neurotrauma 1997, 14:637–650.PubMedCrossRefGoogle Scholar
  50. 50.
    Rothermich NO: The fate of rectally administered radioactive indomethacin in humnan subjects. Clin Pharmacol Ther 1971, 12:300–301.Google Scholar
  51. 51.
    Bannwarth B, Netter P, Lapicque F, et al.: Plasma and cerebrospinal fluid concentrations of indomethacin in human. Euro J Clin Pharmacol 1990, 38:343–346.CrossRefGoogle Scholar
  52. 52.
    Frolich JC: A classification of NSAIDs according to the relative inhibition of cyclooxygenase isoenymes. Trends Pharmacol Sci 1997, 18:30–34.PubMedCrossRefGoogle Scholar
  53. 53.
    Dimitriadou V, Buzzi MG, Theoharides TC, Moskowitz MA: Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation. Neuroscience 1992, 48:187–203.PubMedCrossRefGoogle Scholar
  54. 54.
    Pitcher GM, Henry JL: Mediation and modulation by eicosanoids of responses of spinal dorsal horn neurons to glutamate and substance P receptor agonists: results with indomethacin in the rat in vivo. Neuroscience 1999, 93:1109–1121.PubMedCrossRefGoogle Scholar
  55. 55.
    Pitcher GM, Henry JL: NSAID-induced cyclooxygenase inhibition differentially depresses long-lasting versus brief synaptically elicited responses of rat spinal dorsal horn neurons in vivo. Pain 1999, 82:173–186.PubMedCrossRefGoogle Scholar
  56. 56.
    Du ZY, Li XY: Inhibitory effects of indomethacin on interleukin-1 and nitric oxide production in rat microglia in vitro. Int J Immunopharmacol 1999, 21:219–225.PubMedCrossRefGoogle Scholar
  57. 57.
    Thomsen LL, Olesen J: Nitric oxide theory of migraine. Clin Neurosci 1998, 1:28–33.Google Scholar
  58. 58.
    Lassen LH, Ashina M, Christiansen I, et al.: Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks. Cephalalgia 1998, 18:27–32.PubMedCrossRefGoogle Scholar
  59. 59.
    Goadsby PJ, Uddman R, Edvinsson L: Cerebral vasodilation in the cat involves nitric oxide from parasympathetic nerves. Brain Res 1996, 707:110–118.PubMedCrossRefGoogle Scholar
  60. 60.
    Uddman R, Tajti J, Moller S, et al.: Neuronal messenger molecules and peptide receptors distribution in the human cranial parasympathetic ganglia. Cephalalgia 1999, 19:392.Google Scholar
  61. 61.
    Clemmesen JO, Hansen BA, Larsen FS: Indomethacin normalizes intracranial pressure in acute liver failure: a 23-year-old woman treated with indomethacin. Hepatology 1997, 26:1423–1425.PubMedCrossRefGoogle Scholar
  62. 62.
    Jensen K, Öhrström J, Cold GE, Astrup J: The effects of indomethacin on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients with severe head injury and intracranial hypertension. Acta Neurochir (Wien) 1991, 108:116–121.CrossRefGoogle Scholar
  63. 63.
    Biestro AA, Alberti RA, Soca AE, et al.: Use of indomethacin in brain-injured patients with cerebral perfusion pressure impairment: preliminary report. J Neurosurg 1995, 83:627–630.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • David W. Dodick
    • 1
  1. 1.Department of NeurologyMayo Medical School, Mayo ClinicScottsdaleUSA

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