CNS Drugs

, Volume 22, Issue 12, pp 995–1004 | Cite as

Medication Overuse Headache

Awareness, Detection and Treatment
  • Alan M. RapoportEmail author
Review Article


Episodic migraine is a disabling painful disease that can affect the normal function of daily routine activities such as performance at work and school, and home and social relationships. In addition to the physical disability during migraine, between attacks many patients experience a condition referred to as interictal burden, which can present as pre-event worry about future attacks and can result in the anticipatory use and/or overuse of acute care medications. The overuse of medication can often lead to medication overuse headaches (MOHs) and chronic migraine. Unfortunately, patients, and even some physicians, are often unaware of this phenomenon. Therefore, it is important for knowledgeable physicians to raise awareness and to address the risks of medication overuse with their patients through effective communication. Future management of medication overuse should include detoxification and a comprehensive programme that includes the use of preventive medications such as sodium valproate (divalproex sodium) and topiramate in order to reduce dependency on acute care medication. Also, MOHs may be most effectively managed with the initiation of preventive treatment prior to detoxification, in addition to the decreased use of acute care medication. A long-term treatment plan, including behavioural therapy, migraine preventive medication and appropriate acute care therapy, may be optimal in treating patients with MOHs.


Migraine Botulinum Toxin Topiramate Chronic Migraine Ergotamine 
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.



Dr Rapoport has served on speakers’ bureaus for Endo Pharmaceuticals, GlaxoSmithKline, Merck, Ortho-McNeil and Pfizer Inc., and has participated on advisory boards for Allergan, Endo Pharmaceuticals, Merck, NuPathe and Ortho-McNeil Neurologics. Dr Rapoport has previously received research grants from Ortho-McNeil. Editorial support was provided by Ann Yeung of Phase Five Communications (New York, NY, USA), with funding from Ortho-McNeil Neurologics.


  1. 1.
    Bigal ME, Lipton RB. When migraine progresses: transformed or chronic migraine. Expert Rev Neurother 2006; 6: 297–306PubMedCrossRefGoogle Scholar
  2. 2.
    Colas R, Munoz P, Temprano R, et al. Chronic daily headache with analgesic overuse: epidemiology and impact on quality of life. Neurology 2004; 62: 1338–42PubMedCrossRefGoogle Scholar
  3. 3.
    International Classification of Disorders, Committee of the International Headache Society. Classification and diagnosis criteria for headache disorders, cranial neuralgia and facial pain. Cephalalgia 2004; 24Suppl. 1: 1–150Google Scholar
  4. 4.
    Katsarava Z, Schneeweiss S, Kurth T, et al. Incidence and predictors for chronicity of headache in patients with episodic migraine. Neurology 2004; 62: 788–90PubMedCrossRefGoogle Scholar
  5. 5.
    Scher AI, Stewart WF, Ricci JA, et al. Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain 2003; 106: 81–9PubMedCrossRefGoogle Scholar
  6. 6.
    Cupini LM, Calabresi P. Medication-overuse headache: pathophysiological insights. J Headache Pain 2005; 6: 199–202PubMedCrossRefGoogle Scholar
  7. 7.
    Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. Lancet 2004; 3: 475–83CrossRefGoogle Scholar
  8. 8.
    Kudrow L. Paradoxical effects of frequent analgesic use. Adv Neurol 1982; 33: 335–41PubMedGoogle Scholar
  9. 9.
    Rapoport A. Analgesic rebound headache. Headache 1988; 28: 662–5PubMedCrossRefGoogle Scholar
  10. 10.
    Rapoport A, Stang P, Gutterman DL, et al. Analgesic rebound headache in clinical practice: data from a physician survey. Headache 1996; 36: 14–9PubMedCrossRefGoogle Scholar
  11. 11.
    Ayzenberg I, Obermann M, Nyhuis P, et al. Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures. Cephalalgia 2006; 26: 1106–14PubMedCrossRefGoogle Scholar
  12. 12.
    Meskunas CA, Tepper SJ, Rapoport AM, et al. Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period. Headache 2006; 46: 766–72PubMedCrossRefGoogle Scholar
  13. 13.
    Lake III AE. Medication overuse headache: biobehavioral issues and solutions. Headache 2006; 46Suppl. 3: S88–97PubMedCrossRefGoogle Scholar
  14. 14.
    Bigal ME, Lipton RB. Modifiable risk factors for migraine progression. Headache 2006; 46: 1334–43PubMedCrossRefGoogle Scholar
  15. 15.
    Sances G, Ghiotto N, Loi M, et al. A CARE pathway in medication-overuse headache: the experience of the Headache Centre in Pavia. J Headache Pain 2005; 6: 307–9PubMedCrossRefGoogle Scholar
  16. 16.
    Lipton RB, Bigal E, Diamond M, et al., on behalf of the AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007; 6: 343–9CrossRefGoogle Scholar
  17. 17.
    Dodick D, Freitag F. Evidence-based understanding of medication-overuse headache: clinical implications. Headache 2006; 46Suppl. 4: S202–11PubMedCrossRefGoogle Scholar
  18. 18.
    Couch JR. Rebound-withdrawal headache (medication overuse headache). Curr Treat Opt Neurol 2006; 8: 11–9CrossRefGoogle Scholar
  19. 19.
    Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology 2002; 59: 1011–4PubMedCrossRefGoogle Scholar
  20. 20.
    Dodick DW, Silberstein S, Saper J, et al. The impact of topiramate on health-related quality of life indicators in chronic migraine. Headache 2007; 47: 1398–408PubMedCrossRefGoogle Scholar
  21. 21.
    D’Amico D, Usai S, Grazzi L, et al. Quality of life and disability in primary chronic daily headaches. Neurol Sci 2003; 24Suppl. 2: S97–100PubMedGoogle Scholar
  22. 22.
    Couch JR. Can medication overuse headache be treated by abrupt withdrawal of the overused agent? Nat Clin Pract Neurol 2006; 2: 654–5PubMedCrossRefGoogle Scholar
  23. 23.
    Katsarava Z, Limmroth V, Finke M, et al. Rates and predictors for relapse in medication overuse headache: a 1-year prospective study. Neurology 2003; 60: 1682–3PubMedCrossRefGoogle Scholar
  24. 24.
    Relja G, Granato A, Bratina A, et al. Outcome of medication overuse headache after abrupt in-patient withdrawal. Cephalalgia 2006; 26: 589–95PubMedCrossRefGoogle Scholar
  25. 25.
    Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs structured detoxification programmes for medication overuse headache: a prospective, randomized open-label trial in transformed migraine patients with low medical needs. Cephalalgia 2006; 26: 1097–105PubMedCrossRefGoogle Scholar
  26. 26.
    Mei D, Ferraro D, Zelano G, et al. Topiramate and triptans revert chronic migraine with medication overuse to episodic migraine. Clin Neuropharmacol 2006; 29: 269–75PubMedCrossRefGoogle Scholar
  27. 27.
    Zeeberg P, Olesen J, Jensen R. Probable medication-overuse headache. Neurology 2006; 66: 1894–8PubMedCrossRefGoogle Scholar
  28. 28.
    Olesen J, Bousser M-G, Diener H-C, et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006; 26: 742–6PubMedCrossRefGoogle Scholar
  29. 29.
    Pascual J, Fite B, Lopez-Gil A. Comparison of triptan tablet consumption per attack: a prospective study of migraineurs in Spain. Headache 2002; 42: 93–8PubMedCrossRefGoogle Scholar
  30. 30.
    Boes CJ, Black DF, Dodick DW. Pathophysiology and management of transformed migraine and medication overuse headache. Semin Neurol 2006; 26: 232–41PubMedCrossRefGoogle Scholar
  31. 31.
    Calabresi P, Cupini LM. Medication-overuse headache: similarities with drug addiction. Trends Pharmacol Sci 2005; 26: 62–8PubMedCrossRefGoogle Scholar
  32. 32.
    Fumai A, Laureys S, Di Clemente L, et al. Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine. Brain 2006; 129: 543–50Google Scholar
  33. 33.
    Katsarava Z, Jensen R. Medication-overuse headache: where are we now? Curr Opin Neurol 2007; 20: 326–30PubMedCrossRefGoogle Scholar
  34. 34.
    Smith TR, Stoneman J. Medication overuse headache from antimigraine therapy: clinical features, pathogenesis and management. Drugs 2004; 64: 2503–14PubMedCrossRefGoogle Scholar
  35. 35.
    Fuh JL, Wang SJ, Lu SR, et al. Does medication overuse headache represent a behavior of dependence? Pain 2005; 119: 49–55PubMedCrossRefGoogle Scholar
  36. 36.
    Sheftell FD, Atlas SJ. Migraine and psychiatric comorbidity: from theory and hypotheses to clinical application. Headache 2002; 42: 934–44PubMedCrossRefGoogle Scholar
  37. 37.
    Hahn SR, Nelson MR, Lipton RB. Provider-patient migraine discussions: results of American Migraine Communication Study (AMCS). 58th Annual Meeting of the American Academy of Neurology; 2006 Apr 1–8; San Diego (CA)Google Scholar
  38. 38.
    Hahn SR, Cady RK, Nelson MR, et al. Improving healthcare professional-patient communication to promote more effective assessment of migraine impairment during and between attacks: results of the American Migraine Communication Study (AMCS) phase II. Diamond Headache Clinic’s 20th Annual Practicing Physician’s Approach to the Difficult Headache Patient; 2007 Feb 13–17; Rancho Mirage (CA)Google Scholar
  39. 39.
    Boyle D, Dwinnell B, Platt F. Invite, listen, and summarize: a patient-centered communication technique. Acad Med 2005; 80: 29–32PubMedCrossRefGoogle Scholar
  40. 40.
    Martin LR, Jahng KH, Golin CE, et al. Physician facilitation of patient involvement in care: correspondence between patient and observer reports. Behav Med 2003; 28: 159–64PubMedCrossRefGoogle Scholar
  41. 41.
    Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. MIGR-002 Study Group. JAMA 2004; 291: 965–73PubMedCrossRefGoogle Scholar
  42. 42.
    Edmeads JG, Gawel MJ, Vickers J. Strategies for diagnosing and managing medication-induced headache. Can Fam Physician 1997; 43: 1249–54PubMedGoogle Scholar
  43. 43.
    Frediani F, Cannata AP, Magnoni A, et al. The patient with medication overuse: clinical management problems. Neurol Sci 2003; 24Suppl. 2: S108–11PubMedGoogle Scholar
  44. 44.
    Sands GH. A protocol for butalbital, aspirin and caffeine (BAC) detoxification in headache patients. Headache 1990; 30: 491–6PubMedCrossRefGoogle Scholar
  45. 45.
    Loder E, Biondi D. Oral phenobarbital loading: a safe and effective method of withdrawing patients with headache from butalbital compounds. Headache 2003; 43(8): 904–9PubMedCrossRefGoogle Scholar
  46. 46.
    Zeeberg P, Olesen J, Jensen R. Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness. Cephalalgia 2006; 26: 1192–8PubMedCrossRefGoogle Scholar
  47. 47.
    Andrasik F. Behavioral treatment of migraine: current status and future directions. Expert Rev Neurother 2004; 4: 403–13PubMedCrossRefGoogle Scholar
  48. 48.
    Fanciullacci M, De Cesaris F. Preventing chronicity of migraine. J Headache Pain 2005; 6: 331–3PubMedCrossRefGoogle Scholar
  49. 49.
    Schwartz MS, Andrasik F, editors. Biofeedback, a practitioner’s guide. 3rd ed. New York: Guilford Press, 2005Google Scholar
  50. 50.
    Penzien DB, Holroyd KA. Psychosocial interventions in the management of recurrent headache disorders: II. Description of treatment techniques. Behav Med 1994; 20: 64–73PubMedCrossRefGoogle Scholar
  51. 51.
    Hammond DC, editor. Handbook of hypnotic suggestions and metaphors. New York: Norton and Company, 1990Google Scholar
  52. 52.
    Beck AT, Rush AJ, Shaw BF, et al. Cognitive techniques. In: Beck AT, Rush AJ, Shaw BF, et al., editors. Cognitive therapy of depression. New York: Guilford Press, 1979: 142–66Google Scholar
  53. 53.
    Diener HC, Bussone G, Van Oene JC, et al. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. TOPMAT-MIG-201 (TOP-CHROME) Study Group. Cephalalgia 2007; 27: 814–23PubMedCrossRefGoogle Scholar
  54. 54.
    Silberstein SD, Lipton RB, Dodick DW, et al., on behalf of the Topiramate Chronic Migraine Study Group. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 2007; 47: 170–80PubMedCrossRefGoogle Scholar
  55. 55.
    Silberstein SD, Neto W, Schmitt J, et al. Topiramate in migraine prevention: results of a large controlled trial. MIGR-001 Study Group. Arch Neurol 2004; 61: 490–5Google Scholar
  56. 56.
    Goadsby PJ, Diener H-C, Bussone G, et al., on behalf of the TOPMAT-MIG-201 Investigators Group. Assessing the efficacy and safety of topiramate for the prevention of chronic migraine. 6th Meeting of the European Headache Federation; 2006 Apr 26; ValenciaGoogle Scholar
  57. 57.
    Klapper J, on behalf of the Divalproex Sodium in Migraine Prophylaxis Study Group. Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia 1997; 17(2): 103–8PubMedCrossRefGoogle Scholar
  58. 58.
    Mathew NT, Saper JR, Silberstein SD, et al. Migraine prophylaxis with divalproex. Arch Neurol 1995; 52: 281–6PubMedCrossRefGoogle Scholar
  59. 59.
    Landy SH, Baker JD. Divalproex ER prophylaxis in migraineurs with probable chronic migraine and probable medicationoveruse headache: a case series. Pain Pract 2004; 4: 292–4PubMedCrossRefGoogle Scholar
  60. 60.
    Depakote® (divalproex sodium): product information. North Chicago (IL): Abbott Laboratories, 2006 JanGoogle Scholar
  61. 61.
    Diener HC, Tfelt-Hansen P, Dahlöf C, et al. Topiramate in migraine prophylaxis: results from a placebo-controlled trial with propranolol as an active control. MIGR-003 Study Group. J Neurol 2004; 251: 943–50Google Scholar
  62. 62.
    Dodick DW, Bigal ME, Silberstein S, et al. Efficacy of topiramate treatment for chronic migraine in patients with medication overuse. Diamond Headache Clinic’s 20th Annual Practicing Physician’s Approach to the Difficult Headache Patient; 2007 Feb 13–17; Rancho Mirage (CA)Google Scholar
  63. 63.
    Mathew NT. Antiepileptic drugs in migraine prevention. Headache 2001; 41Suppl. 1: S18–24PubMedCrossRefGoogle Scholar
  64. 64.
    Bigal ME, Krymchantowski AV, Rapoport AM. Prophylactic migraine therapy: emerging treatment options. Curr Pain Headache Rep 2004; 8: 178–84PubMedCrossRefGoogle Scholar
  65. 65.
    Kaniecki R. Neuromodulators for migraine prevention. Headache 2008; 48: 586–600PubMedCrossRefGoogle Scholar
  66. 66.
    Calabresi P, Galletti F, Rossi C, et al. Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms. Trends Pharmacol Sci 2007; 28: 188–95PubMedCrossRefGoogle Scholar
  67. 67.
    Johannessen Landmark C. Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs 2008; 22: 27–47PubMedCrossRefGoogle Scholar
  68. 68.
    Spierings EL. Migraine mechanism and management. Otolaryngol Clin North Am 2003; 36: 1063–78PubMedCrossRefGoogle Scholar
  69. 69.
    White HS. Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache 2005; 45Suppl. 1: S48–56PubMedCrossRefGoogle Scholar
  70. 70.
    Kuzniecky R, Ho S, Pan J, et al. Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Neurology 2002; 58: 368–72PubMedCrossRefGoogle Scholar
  71. 71.
    Eross EJ, Gladstone JP, Lewis S, et al. Duration of migraine is a predictor for response to botulinum toxin type A. Headache 2005; 45: 308–14PubMedCrossRefGoogle Scholar
  72. 72.
    Evers S. Status on the use of botulinum toxin for headache disorders. Curr Opin Neurol 2006; 19: 310–5PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of NeurologyThe David Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.The New England Center for HeadacheStamfordUSA

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