Current Pain and Headache Reports

, Volume 15, Issue 2, pp 108–117 | Cite as

Serotonergic Agents in the Management of Cluster Headache

Article

Abstract

Cluster headache is a highly disabling primary headache disorder, characterized by unilateral headache attacks occurring in association with cranial autonomic symptoms. Serotonergic agents, such as the ergot alkaloids, have traditionally been used for the acute and preventive treatment of cluster headache and other primary headaches. Although it initially was thought that their efficacy was due solely to the vasoconstriction of extracranial cerebral vessels, new mechanisms of action of these drugs have been ascertained as a consequence of advances in elucidation of the pathogenesis of primary headaches and the development of triptans. This article reviews the current knowledge about serotonergic agonists and antagonists used in the management of cluster headache, focusing on their mechanisms of action and on the possible role of serotonin system dysfunction in this complex disorder.

Keywords

Cluster headache Serotonin 5-HT Receptors Sumatriptan Zolmitriptan Ergotamine DHE Methysergide Lithium Pizotifen Lysergic acid 

Notes

Disclosures

G. Lambru: none. Dr. Manjit Matharu serves on the advisory board for Allergan, and has received payment for the development of educational presentations from Allergan and Medtronic.

References

Papers of particular interest, published recently, have been highlighted as • Of importance

  1. 1.
    Headache Classification Committee of The International Headache Society. The International Classification of Headache Disorders 2nd edition. Cephalalgia. 2004;24(Supplement 1):1–195.Google Scholar
  2. 2.
    • Jeong HJ, Chenu D, Johnson EE, Connor M, Vaughan CW: Sumatriptan inhibits synaptic transmission in the rat midbrain periaqueductal grey. Mol Pain 2008, 4:54. This study in animal models suggested a more central and generalized role of triptans in trigeminal pain modulation. PubMedCrossRefGoogle Scholar
  3. 3.
    Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev. 1992;72:165–229.PubMedGoogle Scholar
  4. 4.
    • Baron EP, Tepper SJ: Revisiting the role of ergots in the treatment of migraine and headache. Headache 2010, 50:1353–1361. This is a good review article that revisits the role of ergots in primary headache disorders. PubMedCrossRefGoogle Scholar
  5. 5.
    Hamel E. Serotonin and migraine: biology and clinical implications. Cephalalgia. 2007;27:1293–300.PubMedCrossRefGoogle Scholar
  6. 6.
    Supornsilpchai W, Sanguanrangsirikul S, Maneesri S, Srikiatkhachorn A. Serotonin depletion, cortical spreading depression, and trigeminal nociception. Headache. 2006;46:34–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Waldenlind E, Ross SB, Saaf J, Ekbom K, Wetterberg L. Concentration and uptake of 5-hydroxytryptamine in platelets from cluster headache and migraine patients. Cephalalgia. 1985;5:45–54.PubMedCrossRefGoogle Scholar
  8. 8.
    D'Andrea G, Granella F, Alecci M, Manzoni GC. Serotonin metabolism in cluster headache. Cephalalgia. 1998;18:94–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Leone M, Attanasio A, Croci D, et al. The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity. Cephalalgia. 1997;17:666–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Pinessi L, Rainero I, Valfre W, et al. Abnormal 5-HT1D receptor function in cluster headache: a neuroendocrine study with sumatriptan. Cephalalgia. 2003;23:354–60.PubMedCrossRefGoogle Scholar
  11. 11.
    Berde B, Schild HO. Ergot alkaloids and related compounds. Berlin: Springer; 1978.Google Scholar
  12. 12.
    Silberstein SD, McCrory DC. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache. 2003;43:144–66.PubMedCrossRefGoogle Scholar
  13. 13.
    Buzzi MG, Moskowitz MA, Peroutka SJ, Byun B. Further characterization of the putative 5-HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater. Br J Pharmacol. 1991;103:1421–8.PubMedGoogle Scholar
  14. 14.
    Hoskin KL, Kaube H, Goadsby PJ. Central activation of the trigeminovascular pathway in the cat is inhibited by dihydroergotamine. A c-Fos and electrophysiological study. Brain. 1996;119(Pt 1):249–56.PubMedCrossRefGoogle Scholar
  15. 15.
    Horton BT. The use of histamine in the treatment of specific types of headaches. JAMA. 1941;116:377–83.Google Scholar
  16. 16.
    Horton BT, Ryan R, Reynolds JL. Clinical observations on the use of EC110, a new agent for the treatment of headache. Mayo Clin Proc. 1948;23:105–8.PubMedGoogle Scholar
  17. 17.
    Magee KR, Westerberg MR, DeJong RM. Treatment of headache with ergotamine-caffeine suppositories. Neurology. 1952;2:477–80.PubMedGoogle Scholar
  18. 18.
    Kudrow L. Response of cluster headache attacks to oxygen inhalation. Headache. 1981;21:1–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Speed 3rd WG. Ergotamine tartrate inhalation: a new approach to the management of recurrent vascular headaches. Am J Med Sci. 1960;240:327–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Graham JR, Malvea BP, Gramm HF. Aerosol ergotamine tartrate for migraine and Horton's syndrome. N Engl J Med. 1960;263:802–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Kudrow L. Cluster Headache:Mechanisms and Management. Oxford, New York: Oxford University Press; 1980.Google Scholar
  22. 22.
    Ekbom K. Ergotamine tartrate orally in Horton’s ‘histaminic cephalalgia’ (also called Harris’s ‘ciliary neuralgia’). Acta Psychiatrica et Neurologica. 1947;46:106–13.Google Scholar
  23. 23.
    Symonds C. A particular variety of headache. Brain. 1956;79:217–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Meyler WJ. Side effects of ergotamine. Cephalalgia. 1996;16:5–10.PubMedCrossRefGoogle Scholar
  25. 25.
    Horton BT. Histaminic cephalgia. J Lancet. 1952;72:92–8.PubMedGoogle Scholar
  26. 26.
    Dodick DW, Rozen TD, Goadsby PJ, Silberstein SD. Cluster headache. Cephalalgia. 2000;20:787–803.PubMedCrossRefGoogle Scholar
  27. 27.
    Andersson PG, Jespersen LT. Dihydroergotamine nasal spray in the treatment of attacks of cluster headache. A double-blind trial versus placebo. Cephalalgia. 1986;6:51–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Shrewsbury SB, Cook RO, Taylor G, et al. Safety and pharmacokinetics of dihydroergotamine mesylate administered via a Novel (Tempo) inhaler. Headache. 2008;48:355–67.PubMedCrossRefGoogle Scholar
  29. 29.
    Silberstein S, Kori S, Tepper S, et al. Efficacy and tolerability of MAP0004, a novel inhaled therapy, in treating acute migraine. Cephalalgia. 2009;29 Suppl 1:12–3.Google Scholar
  30. 30.
    Mather PJ, Silberstein SD, Schulman EA, Hopkins MM. The treatment of cluster headache with repetitive intravenous dihydroergotamine. Headache. 1991;31:525–32.PubMedCrossRefGoogle Scholar
  31. 31.
    Magnoux E, Zlotnik G. Outpatient intravenous dihydroergotamine for refractory cluster headache. Headache. 2004;44:249–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Tyagi A, Matharu ML. Evidence base for the medical treatments used in cluster headache. Curr Pain Headache Rep. 2009;13:168–78.PubMedCrossRefGoogle Scholar
  33. 33.
    Sicuteri F. Prophylactic and therapeutic properties of 1-methylysergic acid butanolamide in migraine. Int Arch Allergy. 1959;15:300–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Curran DA, Hinterberger H, Lance JW. Methysergide. Research and Clinical Studies in Headache. 1967;1:74–122.Google Scholar
  35. 35.
    Krabbe A. Limited efficacy of methysergide in cluster headache. A clinical experience. Cephalalgia. 1989;9 Suppl 10:404–5.Google Scholar
  36. 36.
    Matharu MS, Boes CJ, Goadsby PJ. Management of trigeminal autonomic cephalgias and hemicrania continua. Drugs. 2003;63:1637–77.PubMedCrossRefGoogle Scholar
  37. 37.
    Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associated with methysergide therapy for headache. N Engl J Med. 1966;274:360–8.CrossRefGoogle Scholar
  38. 38.
    Silberstein SD. Methysergide. Cephalalgia. 1998;18:421–35.PubMedCrossRefGoogle Scholar
  39. 39.
    Blakeborough P, Fowler PA, Ashford EA. The use of sumatriptan in patients taking migraine prophylactic agents. Cephalalgia. 1993;13:163.Google Scholar
  40. 40.
    Liston H, Bennett L, Usher Jr B. Nappi J: The association of the combination of sumatriptan and methysergide in myocardial infarction in a premenopausal woman. Arch Intern Med. 1999;159:511–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Mueller L, Gallagher RM, Ciervo CA. Methylergonovine maleate as a cluster headache prophylactic: a study and review. Headache. 1997;37:437–42.PubMedCrossRefGoogle Scholar
  42. 42.
    Schiff PL. Ergot and its alkaloids. Am J Pharm Educ. 2006;70:98.PubMedGoogle Scholar
  43. 43.
    Fantegrossi WE, Murnane KS, Reissig CJ. The behavioral pharmacology of hallucinogens. Biochem Pharmacol. 2008;75:17–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Sicuteri F. Prophylactic Treatment of Migraine by Means of Lysergic Acid Derivatives. Triangle. 1963;67:116–25.PubMedGoogle Scholar
  45. 45.
    Sewell RA, Halpern JH, Pope Jr HG. Response of cluster headache to psilocybin and LSD. Neurology. 2006;66:1920–2.PubMedCrossRefGoogle Scholar
  46. 46.
    Clark LD, Bliss EL. Psychopharmacological studies of lysergic acid diethylamide (LSD-25) intoxication; effects of premedication with BOL-128 (2-bromo-d-lysergic acid diethylamide), mescaline, atropine, amobarbital, and chlorpromazine. AMA Arch Neurol Psychiatry. 1957;78:653–5.PubMedGoogle Scholar
  47. 47.
    • Karst M, Halpern JH, Bernateck M, Passie T. The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: an open, non-randomized case series. Cephalalgia 2010, 30:1140–1144. This study provides evidence of the efficacy of a non-hallucinogen LSD analogue in a small series of patients with cluster headache. PubMedCrossRefGoogle Scholar
  48. 48.
    Treatment of acute cluster headache with sumatriptan. The Sumatriptan Cluster Headache Study Group. N Engl J Med. 1991;325:322–6.CrossRefGoogle Scholar
  49. 49.
    Ekbom K, Monstad I, Prusinski A, et al. Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. The Sumatriptan Cluster Headache Study Group. Acta Neurol Scand. 1993;88:63–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Ekbom K, Krabbe A, Micieli G, et al. Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg). Sumatriptan Cluster Headache Long-term Study Group. Cephalalgia. 1995;15:230–6. Published erratum appears in Cephalalgia 1995, 15:446.PubMedCrossRefGoogle Scholar
  51. 51.
    Göbel H, Lindner V, Heinze A, et al. Acute therapy for cluster headache with sumatriptan: findings of a one-year long-term study. Neurology. 1998;51:908–11.PubMedGoogle Scholar
  52. 52.
    van Vliet JA, Bahra A, Martin V, et al. Intranasal sumatriptan is effective in the treatment of acute cluster headache—a double-blind placebo-controlled crossover study. Cephalalgia. 2001;21:270–1.Google Scholar
  53. 53.
    Cittadini E, May A, Straube A, et al. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol. 2006;63:1537–42.PubMedCrossRefGoogle Scholar
  54. 54.
    • Rapoport AM, Mathew NT, Silberstein SD, et al.: Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study. Neurology 2007, 69:821–826. This recent randomized control trial demonstrates the efficacy of intranasal zolmitriptan in cluster headache. PubMedCrossRefGoogle Scholar
  55. 55.
    Bahra A, Gawel MJ, Hardebo JE, et al. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54:1832–9.PubMedGoogle Scholar
  56. 56.
    Eekers PJ, Koehler PJ. Naratriptan prophylactic treatment in cluster headache. Cephalalgia. 2001;21:75–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Mulder LJ, Spierings EL. Naratriptan in the preventive treatment of cluster headache. Cephalalgia. 2002;22:815–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Siow HC, Pozo-Rosich P, Silberstein SD. Frovatriptan for the treatment of cluster headaches. Cephalalgia. 2004;24:1045–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Wober C, Vigl K, Wessely P. Eletriptan for short-term prophylaxis of cluster headache. Cephalalgia. 2002;22:584.Google Scholar
  60. 60.
    Sicuteri F, Franchi G, Del Biancho PL. An antaminic drug, BC 105, in the prophylaxis of migraine. Pharmacological, clinical, and therapeutic experiences. Int Arch Allergy Appl Immunol. 1967;31:78–93.PubMedCrossRefGoogle Scholar
  61. 61.
    Ekbom K. Prophylactic treatment of cluster headache with a new serotonin antagonist, BC 105. Acta Neurol Scand. 1969;45:601–10.PubMedCrossRefGoogle Scholar
  62. 62.
    Speight TM, Avery GS. Pizotifen (BC-105): a review of its pharmacological properties and its therapeutic efficacy in vascular headaches. Drugs. 1972;3:159–203.PubMedCrossRefGoogle Scholar
  63. 63.
    Pasquali L, Busceti CL, Fulceri F, et al. Intracellular pathways underlying the effects of lithium. Behav Pharmacol. 2010;21:473–92.PubMedCrossRefGoogle Scholar
  64. 64.
    Subhash MN, Vinod KY, Srinivas BN. Differential effect of lithium on 5-HT1 receptor-linked system in regions of rat brain. Neurochem Int. 1999;35:337–43.PubMedCrossRefGoogle Scholar
  65. 65.
    Knapp S, Mandell AJ. Effects of lithium chloride on parameters biosynthetic capacity for 5-hydroxytryptamin in rat brain. J Pharmacol Exp Ther. 1975;193:812–23.PubMedGoogle Scholar
  66. 66.
    Ekbom K. Lithium in the treatment of chronic cluster headache. Headache. 1977;17:39–40.PubMedCrossRefGoogle Scholar
  67. 67.
    Ekbom K. Lithium for cluster headache: review of the literature and preliminary results of long-term treatment. Headache. 1981;21:132–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Bussone G, Leone M, Peccarisi C, Micieli G, Granella F, Magri M, et al. Double blind comparison of lithium and verapamil in cluster headache prophylaxis. Headache. 1990;30:411–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Steiner TJ, Hering R, Couturier EG, et al. Double-blind placebo-controlled trial of lithium in episodic cluster headache [see comments]. Cephalalgia. 1997;17:673–5.PubMedCrossRefGoogle Scholar
  70. 70.
    Baf MH, Subhash MN, Lakshmana KM, Rao BS. Sodium valproate induced alterations in monoamine levels in different regions of the rat brain. Neurochem Int. 1994;24:67–72.PubMedCrossRefGoogle Scholar
  71. 71.
    El Amrani M, Massiou H, Bousser M. A negative trial of sodium valproate in cluster headache: methodological issues. Cephalalgia. 2002;22:205–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Eide PK, Hole K. The role of 5-hydroxytryptamine (5-HT) receptor subtypes and plasticity in the 5-HT systems in the regulation of nociceptive sensitivity. Cephalalgia. 1993;13:75–85.PubMedCrossRefGoogle Scholar
  73. 73.
    Donaldson C, Boers PM, Hoskin KL, et al. The role of 5-HT1B and 5-HT1D receptors in the selective inhibitory effect of naratriptan on trigeminovascular neurons. Neuropharmacology. 2002;42:374–85.PubMedCrossRefGoogle Scholar
  74. 74.
    Goadsby PJ, Knight YE. Direct evidence for central sites of action of zolmitriptan (311C90): an autoradiographic study in cat. Cephalalgia. 1997;17:153–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Hedlund PB. The 5-HT7 receptor and disorders of the nervous system: an overview. Psychopharmacology (Berl). 2009;206(3):345–54.CrossRefGoogle Scholar
  76. 76.
    Wang X, Fang Y, Liang J, et al. Selective inhibition of 5-HT7 receptor reduces CGRP release in an experimental model for migraine. Headache. 2010;50:579–87.PubMedCrossRefGoogle Scholar
  77. 77.
    Terron JA, Martinez-Garcia E. 5-HT7 receptor-mediated dilatation in the middle meningeal artery of anesthetized rats. Eur J Pharmacol. 2007;560:56–60.PubMedCrossRefGoogle Scholar
  78. 78.
    Brenchat A, Romero L, García M, et al. 5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice. Pain. 2009;141:239–47.PubMedCrossRefGoogle Scholar
  79. 79.
    Terron JA. Is the 5-HT(7) receptor involved in the pathogenesis and prophylactic treatment of migraine? Eur J Pharmacol. 2002;439:1–11.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Headache Group, Institute of Neurology and The National Hospital for Neurology and NeurosurgeryQueen SquareUK

Personalised recommendations