Medication Overuse and Headache

Reference work entry


Medication-overuse headache (MOH) is a chronic, secondary headache disorder caused by the extensive overuse of all known symptomatic anti-headache drugs. Although its prevalence in the general population is limited to 1%, MOH has a major impact on the patient’s quality of life; thus, it creates a high economic burden on society. The ICHD-II guidelines classify MOH into eight subtypes based on the overused medication. Migraine is the most common primary headache complicated by medication overuse. Typically, headaches should resolve or revert to their previous pattern within 2 months after discontinuation of the overused medication, but revised criteria have been published. MOH is often comorbid with many affective disorders; therefore, its management requires a multidisciplinary therapeutic approach, including both pharmaceutical and behavioral treatments. Withdrawal of the overused medication is necessary to improve the headaches, yet MOH frequently recurs. To treat rebound headache from withdrawal, preventive therapy can be started prior to withdrawal of the overused medication. All medications used for the prevention of the primary headache disorders involved in MOH are also effective for the prevention of MOH after withdrawal. Additional treatment of all comorbid conditions, however, is also required.


Obsessive Compulsive Disorder Chronic Migraine Headache Disorder Medication Overuse Episodic Migraine 
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  1. Aaseth K, Grande RB, Kvaerner KJ, Gulbrandsen P, Lundqvist C, Russell MB (2008) Prevalence of secondary chronic headaches in a population-based sample of 30–44-year-old persons. The Akershus study of chronic headache. Cephalalgia 28:705–713PubMedCrossRefGoogle Scholar
  2. Andrasik F, Buse DC, Grazzi L (2009) Behavioral medicine for migraine and medication overuse headache. Curr Pain Headache Rep 13:241–248PubMedCrossRefGoogle Scholar
  3. Bigal ME, Lipton RB (2008) Excessive acute migraine medication use and migraine progression. Neurology 71:1821–1828PubMedCrossRefGoogle Scholar
  4. Bigal ME, Lipton RB (2009) Overuse of acute migraine medications and migraine chronification. Curr Pain Headache Rep 13:301–307PubMedCrossRefGoogle Scholar
  5. Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB (2008a) Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 48:1157–1168PubMedCrossRefGoogle Scholar
  6. Bigal ME, Rapoport AM, Hargreaves R (2008b) Advances in the pharmacologic treatment of tension-type headache. Curr Pain Headache Rep 12:442–446PubMedCrossRefGoogle Scholar
  7. Bodnar RJ, Klein GE (2006) Endogenous opiates and behavior: 2005. Peptides 27:3391–3478PubMedCrossRefGoogle Scholar
  8. Bøe MG, Mygland Å, Salvesen R (2007) Prednisolone does not reduce withdrawal headache: a randomized, double-blind study. Neurology 69:26–31PubMedCrossRefGoogle Scholar
  9. Calabresi P, Cupini LM (2005) Medication-overuse headache: similarities with drug addiction. Trends Pharmacol Sci 26:62–68PubMedCrossRefGoogle Scholar
  10. Cevoli S, Sancisi E, Grimaldi D, Pierangeli G, Zanigni S, Nicodemo M, Cortelli P, Montagna P (2009) Family history for chronic headache and drug overuse as a risk factor for headache chronification. Headache 49(3):412–418PubMedCrossRefGoogle Scholar
  11. Colas R, Muρoz P, Temprano R, Gσmez C, Pascual J (2004) Chronic daily headache with analgesic overuse: epidemiology and impact on quality of life. Neurology 62:1338–1342PubMedGoogle Scholar
  12. Cupini LM, De Murtas M, Costa C, Mancini M, Eusebi P, Sarchielli P, Calabresi P (2009) Obsessive-compulsive disorder and migraine with medication-overuse headache. Headache 49:1005–1013PubMedCrossRefGoogle Scholar
  13. Di Lorenzo C, Sances G, Di Lorenzo G, Rengo C, Ghiotto N, Guaschino E, Perrotta A, Santorelli FM, Grieco GS, Troisi A, Siracusano A, Pierelli F, Nappi G, Casali C (2007) The wolframin His611Arg polymorphism influences medication overuse headache. Neurosci Lett 424:179–184PubMedCrossRefGoogle Scholar
  14. Di Lorenzo C, Di Lorenzo G, Sances G, Ghiotto N, Guaschino E, Grieco GS, Santorelli FM, Casali C, Troisi A, Siracusano A, Pierelli F (2009) Drug consumption in medication overuse headache is influenced by brain-derived neurotrophic factor Val66 Met polymorphism. J Headache Pain 10(5):349–355. Epub 2009 Jun 11PubMedCrossRefGoogle Scholar
  15. Diener HC, Dahlöf CG (1999) Headache associated with chronic use of substances. In: Olesen J, Tfelt-Hansen P, Welch KMA (eds) The headaches, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 156–164Google Scholar
  16. Diener HC, Katsarava Z (2001) Medication overuse headache. Curr Med Res Opin 17(Suppl 1):s17–21. ReviewPubMedCrossRefGoogle Scholar
  17. Diener HC, Limmroth V (2004) Medication-overuse headache: a worldwide problem. Lancet Neurol 3:475–483PubMedCrossRefGoogle Scholar
  18. Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ, TOPMAT-MIG-201(TOP-CHROME) Study Group (2007) Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 27:814–823PubMedCrossRefGoogle Scholar
  19. Dodick DW, Freitag F, Banks J, Saper J, Xiang J, Rupnow M, Biondi D, Greenberg SJ, Hulihan J, CAPSS-277 Investigator Group (2009) Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs. Clin Ther 31:542–559PubMedCrossRefGoogle Scholar
  20. Domingues RB, Silva AL, Domingues SA, Aquino CC, Kuster GW (2009) A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine. Arq Neuropsiquiatr 67(4):973–977PubMedCrossRefGoogle Scholar
  21. Drucker P, Tepper S (1998) Daily sumatriptan for detoxification from rebound. Headache 38:687–690PubMedCrossRefGoogle Scholar
  22. Evers S, Marziniak M (2010) Clinical features, pathophysiology, and treatment of medication-overuse headache. Lancet Neurol 9:391–401PubMedCrossRefGoogle Scholar
  23. Evers S, Bauer B, Suhr S (1996) Ergotamine-induced headache associated with cluster headache. Neurology 46:291PubMedGoogle Scholar
  24. Fontanillas N, Colás R, Muñoz P, Oterino A, Pascual J (2010) Long-term evolution of chronic daily headache with medication overuse in the general population. Headache 50(6):981–988PubMedCrossRefGoogle Scholar
  25. Fumal A, Laureys S, Di Clemente L et al (2006) Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine. Brain 129:543–550PubMedCrossRefGoogle Scholar
  26. Galeotti N, Bartolini A, Ghelardini G (2004) Role of intracellular calcium in acute thermal pain perception. Neuropharmacology 47:935–944PubMedCrossRefGoogle Scholar
  27. Goadsby PJ (2006) Is medication-overuse headache a distinct biological entity? Nat Clin Pract Neurol 2:401PubMedCrossRefGoogle Scholar
  28. Gratacòs M, González JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X (2007) Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry 61:911–922PubMedCrossRefGoogle Scholar
  29. Grazzi L, Usai S, Prunesti A, Bussone G, Andrasik F (2009) Behavioral plus pharmacological treatment versus pharmacological treatment only for chronic migraine with medication overuse after day-hospital withdrawal. Neurol Sci 30(Suppl 1):S117–S119PubMedCrossRefGoogle Scholar
  30. Hagen K, Albretsen C, Vilming ST, Salvesen R, Grønning M, Helde G, Gravdahl G, Zwart JA, Stovner LJ (2009) Management of medication overuse headache: 1-year randomized multicentre open-label trial. Cephalalgia 29(2):221–232. Epub 2008 Sep 24PubMedCrossRefGoogle Scholar
  31. Headache Classification Committee (2006) New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 26:742–746CrossRefGoogle Scholar
  32. Headache Classification Committee of the International Headache Society (ICHD-I) (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8(suppl 7):1–96Google Scholar
  33. Headache Classification Subcommittee of the International Headache Society (ICHD-II) (2004) The international classification of headache disorders, 2nd edn. Cephalalgia 24(Suppl 1):1–160CrossRefGoogle Scholar
  34. Horton BT, Peters GA (1963) Clinical manifestations of excessive use of ergotamine preparations and management of withdrawal effect: report of 52 cases. Headache 3:214–226CrossRefGoogle Scholar
  35. Imai N, Kitamura E, Konishi T, Suzuki Y, Serizawa M, Okabe T (2007) Clinical features of probable medication-overuse headache: a retrospective study in Japan. Cephalalgia 27:1020–1023PubMedCrossRefGoogle Scholar
  36. Jensen R, Bendtsen L (2008) Medication overuse headache in Scandinavia. Cephalalgia 28:1237–1239PubMedCrossRefGoogle Scholar
  37. Katsarava Z, Jensen R (2007) Medication-overuse headache: where are we now? Curr Opin Neurol 20:326–330PubMedCrossRefGoogle Scholar
  38. Katsarava Z, Fritsche G, Muessig M, Diener HC, Limmroth V (2001) Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 57:1694–1698PubMedGoogle Scholar
  39. Katsarava Z, Schneeweiss S, Kurth T, Kroener U, Fritsche G, Eikermann A, Diener HC, Limmroth V (2004) Incidence and predictors for chronicity of headache in patients with episodic migraine. Neurology 62:788–790PubMedGoogle Scholar
  40. Katsarava Z, Dzagnidze A, Kukava M, Mirvelashvili E, Djibuti M, Janelidze M, Jensen R, Stovner LJ, Steiner TJ (2009) Lifting the burden: the global campaign to reduce the burden of headache worldwide and the russian linguistic subcommittee of the international headache society. Primary headache disorders in the Republic of Georgia: prevalence and risk factors. Neurology 73:1796–1803PubMedCrossRefGoogle Scholar
  41. Krymchantowski AV, Barbosa JS (2000) Prednisone as initial treatment of analgesic-induced daily headache. Cephalalgia 20:107–113PubMedCrossRefGoogle Scholar
  42. Lautenbacher S, Krieg JC (1994) Pain perception in psychiatric disorders: a review of the literature. J Psychiatr Res 28:109–122PubMedCrossRefGoogle Scholar
  43. Limmroth V, Katsarava Z, Fritsche G, Przywara S, Diener HC (2002) Features of medication overuse headache following overuse of different acute headache drugs. Neurology 59:1011–1014PubMedGoogle Scholar
  44. Limmroth V, Biondi D, Pfeil J, Schwalen S (2007) Topiramate in patients with episodic migraine: reducing the risk for chronic forms of headache. Headache 47:13–21PubMedCrossRefGoogle Scholar
  45. Linton-Dahlöf P, Linde M, Dahlöf C (2000) Withdrawal therapy improves chronic daily headache associated with long-term misuse of headache medication: a retrospective study. Cephalalgia 20:658–662PubMedGoogle Scholar
  46. Lu SR, Fuh JL, Chen WT, Juang KD, Wang SJ (2001) Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome predictors. Cephalalgia 21:980–986PubMedCrossRefGoogle Scholar
  47. Lundqvist C, Aaseth K, Grande RB, Benth JS, Russell MB (2010) The severity of dependence score correlates with medication overuse in persons with secondary chronic headaches. The Akershus study of chronic headache. Pain 148:487–491PubMedCrossRefGoogle Scholar
  48. Mathew NT (2009) Dynamic optimization of chronic migraine treatment: current and future options. Neurology 72(5 Suppl):S14–S20PubMedCrossRefGoogle Scholar
  49. Mei D, Ferraro D, Zelano G, Capuano A, Vollono C, Gabriele C, Di Trapani G (2006) Topiramate and triptans revert chronic migraine with medication overuse to episodic migraine. Clin Neuropharmacol 29:269–275PubMedCrossRefGoogle Scholar
  50. Merikangas KR, Stevens DE (1997) Comorbidity of migraine and psychiatric disorders. Neurol Clin 15:115–123PubMedCrossRefGoogle Scholar
  51. Meskunas CA, Tepper SJ, Rapoport AM, Sheftell FD, Bigal ME (2006) Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period. Headache 46(5):766–772PubMedCrossRefGoogle Scholar
  52. Mitsikostas DD, Thomas AM (1999) Comorbidity of headache and depressive disorders. Cephalalgia 19:211–217PubMedCrossRefGoogle Scholar
  53. Mitsikostas DD, Vikelis M, Kodounis A, Zaglis D, Xifaras M, Doitsini S, Georgiadis G, Thomas A, Charmoussi S (2010) Migraine recurrence is not associated with depressive or anxiety symptoms. Results of a randomized controlled trial. Cephalalgia 30(6):690–695PubMedGoogle Scholar
  54. Paemeleire K, Bahra A, Evers S, Matharu M, Goadsby PJ (2006) Medication-overuse headache in patients with cluster headache. Neurology 67:109–113PubMedCrossRefGoogle Scholar
  55. Paemeleire K, Evers S, Goadsby PJ (2008) Medication-overuse headache in patients with cluster headache. Curr Pain Headache Rep 12:122–127PubMedCrossRefGoogle Scholar
  56. Pageler L, Katsarava Z, Diener HC, Limmroth V (2008) Prednisone vs. placebo in withdrawal therapy following medication overuse headache. Cephalalgia 28:152–156PubMedGoogle Scholar
  57. Peters GA, Horton BT (1951) Headache: with special reference to the excessive use of ergotamine preparations and withdrawal effects. Mayo Clin Proc 26:153–161Google Scholar
  58. Radat F, Swendsen J (2005) Psychiatric comorbidity in migraine: a review. Cephalalgia 25:165–178PubMedCrossRefGoogle Scholar
  59. Radat F, Creac'h C, Guegan-Massardier E, Mick G, Guy N, Fabre N, Giraud P, Nachit-Ouinekh F, Lantéri-Minet M (2008) Behavioral dependence in patients with medication overuse headache: a cross-sectional study in consulting patients using the DSM-IV criteria. Headache 48:1026–1036PubMedCrossRefGoogle Scholar
  60. Radat F, Creac'h C, Swendsen JD, Lafittau M, Irachabal S, Dousset V, Henry P (2005) Psychiatric comorbidity in the evolution from migraine to medication overuse headache. Cephalalgia 25(7):519–522PubMedCrossRefGoogle Scholar
  61. Rainero I, Ferrero M, Rubino E, Valfrè W, Pellegrino M, Arvat E, Giordano R, Ghigo E, Limone P, Pinessi L (2006) Endocrine function is altered in chronic migraine patients with medication-overuse. Headache 46:597–603PubMedCrossRefGoogle Scholar
  62. Rapoport AM (2008) Medication overuse headache: awareness, detection and treatment. CNS Drugs 22:995–1004PubMedCrossRefGoogle Scholar
  63. Relja G, Granato A, Maria Antonello R, Zorzon M (2004) Headache induced by chronic substance use: analysis of medication overused and minimum dose required to induce headache. Headache 44:148–153PubMedCrossRefGoogle Scholar
  64. Rossi P, Jensen R, Nappi G, Allena M, the COMOESTAS Consortium (2009) A narrative review on the management of medication overuse headache: the steep road from experience to evidence. J Headache Pain 10:407–417PubMedCrossRefGoogle Scholar
  65. Sarchielli P, Rainero I, Coppola F et al (2008) Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine and medication-overuse headache: findings from cerebrospinal fluid. Cephalalgia 28:714–722PubMedCrossRefGoogle Scholar
  66. Silberstein SD, Olesen J, Bousser MG et al; International Headache Society (2005) The international classification of headache disorders, 2nd edn (ICHD-II–revision of criteria for 8.2 Medication-overuse headache. Cephalalgia 25:460–465PubMedCrossRefGoogle Scholar
  67. Silberstein SD, Schulman EA, Hopkins MM (1990) Repetitive intravenous DHE in the treatment of refractory headache. Headache 30:334–339PubMedCrossRefGoogle Scholar
  68. Silberstein SD, Saper J, Stein M, DeGryse R, Turkel C (2010) Onabotulinumtoxin A for treatment of chronic migraine: 56-week analysis of the PREEMPT chronic migraine subgroup with baseline acute headache medication overuse. 62th AAN Annual Meeting, Toronto April 10–17, 2010.Google Scholar
  69. Smith TR (2002) Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache. Headache 42:175–177PubMedCrossRefGoogle Scholar
  70. Srikiatkhachorn A, Anthony M (1996) Serotonin receptor adaptation in patients with analgesic-induced headache. Cephalalgia 16:419–422PubMedCrossRefGoogle Scholar
  71. Srikiatkhachorn A, Govitrapong P, Limthavon C (1994) Up-regulation of 5-HT2 serotonin receptor: a possible mechanism of transformed migraine. Headache 34:8–11PubMedCrossRefGoogle Scholar
  72. Straube A, Pfaffenrath V, Ladwig KH, Meisinger C, Hoffmann W, Fendrich K, Vennemann M, Berger K (2010) Prevalence of chronic migraine and medication overuse headache in Germany-the German DMKG headache study. Cephalalgia 30(2):207–213PubMedGoogle Scholar
  73. Usai S, Grazzi L, D'Amico D, Andrasik F, Bussone G (2009) Psychological variables in chronic migraine with medication overuse before and after inpatient withdrawal: results at 1-year follow-up. Neurol Sci 30(Suppl 1):S125–S127PubMedCrossRefGoogle Scholar
  74. Vieira DS, Naff ah-Mazzacoratti Mda G, Zukerman E, Senne Soares CA, Cavalheiro EA, Peres MF (2007) Glutamate levels in cerebrospinal fluid and triptans overuse in chronic migraine. Headache 47:842–847PubMedCrossRefGoogle Scholar
  75. Weeks RE (2009) Practical strategies for treating chronic migraine with medication overuse: case examples and role play demonstrations. Neurol Sci 30(Suppl 1):S95–S99PubMedCrossRefGoogle Scholar
  76. Wiendels NJ, van der Geest MC, Neven AK, Ferrari MD, Laan LA (2005) Chronic daily headache in children and adolescents. Headache 45:678–683PubMedCrossRefGoogle Scholar
  77. Wiendels NJ, van Haestregt A, Knuistingh Neven A, Spinhoven P, Zitman FG, Assendelft WJ, Ferrari MD (2006a) Chronic frequent headache in the general population: comorbidity and quality of life. Cephalalgia 26:1443–1450PubMedCrossRefGoogle Scholar
  78. Wiendels NJ, Knuistingh Neven A, Rosendaal FR, Spinhoven P, Zitman FG, Assendelft WJ, Ferrari MD (2006b) Chronic frequent headache in the general population: prevalence and associated factors. Cephalalgia 26:1434–1442PubMedCrossRefGoogle Scholar
  79. Worz R (1983) Effects and risks of psychotropic and analgesic combinations. Am J Med 75:139–140PubMedCrossRefGoogle Scholar
  80. Zeeberg P, Olesen J, Jensen R (2006a) Probable medication-overuse headache: the effect of a 2-month drug-free period. Neurology 66:1894–1898PubMedCrossRefGoogle Scholar
  81. Zeeberg P, Olesen J, Jensen R (2006b) Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness. Cephalalgia 26:1192–1198PubMedCrossRefGoogle Scholar
  82. Zeeberg P, Olesen J, Jensen R (2009) Medication overuse headache and chronic migraine in a specialized headache centre: field-testing proposed new appendix criteria. Cephalalgia 29:214–220PubMedCrossRefGoogle Scholar
  83. Zwart JA, Dyb G, Hagen K, Svebak S, Stovner LJ, Holmen J (2004) Analgesic overuse among subjects with headache, neck, and low-back pain. Neurology 62:1540–1544PubMedGoogle Scholar

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© Lifting The Burden 2011

Authors and Affiliations

  1. 1.Neurology DepartmentAthens Naval HospitalAthensGreece
  2. 2.College of MedicineKAIMRC, King Saud Ben Abdulaziz University for Health SciencesRiyadhSaudi Arabia

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