CNS Drugs

, Volume 27, Issue 11, pp 867–877 | Cite as

Medication Overuse Headache: History, Features, Prevention and Management Strategies

  • Joel R. SaperEmail author
  • Arnaldo Neves Da Silva
Leading Article


Medication overuse headache (MOH) is a daily, or almost daily, headache form that arises from overuse of one or more classes of migraine-abortive or analgesic medication. The main classes of drugs that cause MOH are opioids, butalbital-containing mixed analgesics, triptans, ergotamine tartrate derivatives, simple analgesics (except for plain aspirin), and perhaps non-steroidal anti-inflammatory drugs. MOH can be debilitating and results from biochemical and functional brain changes induced by certain medications taken too frequently. At this time, migraine and other primary headache disorders in which migraine or migraine-like elements occur seem exclusively vulnerable to the development of MOH. Other primary headache disorders are not currently believed to be vulnerable. The treatment of MOH consists of discontinuation of the offending drug(s), acute treatment of the withdrawal symptoms and escalating pain, establishing a preventive treatment when necessary, and the implementation of educational and behavioral programs to prevent recidivism. In most patients, MOH can be treated in the outpatient setting but, for the most difficult cases, including those with opioid or butalbital overuse, or in patients with serious medical or behavioral disturbances, effective treatment requires a multidisciplinary, comprehensive headache program, either day-hospital with infusion or an inpatient hospital setting.


Migraine Topiramate Chronic Migraine Chronic Daily Headache Medication Overuse 
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.


The authors have received no funding for the preparation or completion of this manuscript.


The first and all drafts were written exclusively by the authors.

Conflicts of interest

Joel R. Saper, M.D. has served on a Speakers Bureau for Merck and received research grants from Allergan, Merck, St. Jude Medical, Eli Lilly, Pfizer, Vanda, Forest Research Institute, J & J, Endo, Astellas, BMS, SK Lifesciences, Optinose Glaxo and Nu Pathe. He has also served as a consultant for St. Jude Medical, Autonomic Technologies, BMS, Nu Pathe, Merck, Migraine Research Foundation and Arteaus Therapeutic. Dr Da Silva has no potential conflicts of interest to report.


  1. 1.
    Kudrow L. Paradoxical effects of frequent analgesic use. Adv Neurol. 1982;33:335–41.PubMedGoogle Scholar
  2. 2.
    Saper JR. Drug abuse among headache patients. In: Headache disorders: current concepts and treatment strategies. USA: John Wright; 1983. p. 263–78.Google Scholar
  3. 3.
    Saper JR. Migraine. I. classification and pathogenesis. JAMA. 1978;239(22):2380–3.PubMedCrossRefGoogle Scholar
  4. 4.
    Isler H. Headaches combined with overuse of analgesics. In: Carrol JD, Pfaffenrath V, Sjaastad O, editors. Migraine and beta-blockade. Molndal (Sweeden): Hassle; 1985. p. 180–3.Google Scholar
  5. 5.
    Rowsell AR, Neylan C, Wilkinson M. Ergotamine induced headaches in migrainous patients. Headache. 1973;13(2):65–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Saper JR. Migraine: II. Treatment. JAMA. 1978;239(23):2480–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Rapoport AM, Sheftell FD, Weeks RE, Baskin SM. Analgesic rebound headache. In: Proceedings of the Twelfth Meeting of the Scandinavian Migraine Society. 1983. p. 37–38.Google Scholar
  8. 8.
    Saper JR, Jones JM. Ergotamine tartrate dependency: features and possible mechanisms. Clin Neuropharmacol. 1986;9(3):244–56.PubMedCrossRefGoogle Scholar
  9. 9.
    Ferraro S, Grazzi L, Muffatti R, Nava S, Ghielmetti F, Bertolino N, et al. In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas. Headache. 2012;52(10):1520–34.Google Scholar
  10. 10.
    Headache Classification Committee; Olesen J, Bousser MG, Diener HC, Dodick D, First M, et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia. 2006;26(6):742–6.Google Scholar
  11. 11.
    Saper JR, Lake AE, 3rd. Medication overuse headache: type I and type II. Cephalalgia. 2006;26(10):1262.Google Scholar
  12. 12.
    Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache. 2008;48(8):1157–68.PubMedCrossRefGoogle Scholar
  13. 13.
    De Felice M, Ossipov MH, Porreca F. Update on medication-overuse headache. Curr Pain Headache Rep. 2011;15(1):79–83.PubMedCrossRefGoogle Scholar
  14. 14.
    De Felice M, Ossipov MH, Wang R, Lai J, Chichorro J, Meng I, et al. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol. 2010;67(3):325–37.PubMedGoogle Scholar
  15. 15.
    Tepper SJ. Medication-overuse headache. Continuum (Minneapolis Minn). 2012;18(4):807–22.Google Scholar
  16. 16.
    Katsarava Z, Fritsche G, Muessig M, Diener HC, Limmroth V. Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology. 2001;57(9):1694–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Katsarava Z, Jensen R. Medication-overuse headache: where are we now? Curr Opin Neurol. 2007;20(3):326–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Limmroth V, Katsarava Z, Fritsche G, Przywara S, Diener HC. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Bahra A, Walsh M, Menon S, Goadsby PJ. Does chronic daily headache arise de novo in association with regular use of analgesics? Headache. 2003;43(3):179–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Wilkinson SM, Becker WJ, Heine JA. Opiate use to control bowel motility may induce chronic daily headache in patients with migraine. Headache. 2001;41(3):303–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Waeber C, Moskowitz MA. Therapeutic implications of central and peripheral neurologic mechanisms in migraine. Neurology. 2003;61(8 Suppl 4):S9–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Calabresi P, Cupini LM. Medication-overuse headache: similarities with drug addiction. Trends Pharmacol Sci. 2005;26(2):62–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Diener HC, Dahlof CGH. Headache associated with chronic use of substances. In: Olesen J, Tfelt-Hansen P, Welch KMA, editors. The Headaches, 2nd edn. Philadelphia: Lippincott, Williams & Wilkins; 1999. p. 671–878.Google Scholar
  24. 24.
    Castillo J, Munoz P, Guitera V, Pascual J. Kaplan award 1998. Epidemiology of chronic daily headache in the general population. Headache. 1999;39(3):190–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Lipton RB. Tracing transformation: chronic migraine classification, progression, and epidemiology. Neurology. 2009;72(5 Suppl):S3–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Ghiotto N, Sances G, Galli F, Tassorelli C, Guaschino E, Sandrini G, et al. Medication overuse headache and applicability of the ICHD-II diagnostic criteria: 1-year follow-up study (CARE I protocol). Cephalalgia. 2009;29(2):233–43.PubMedCrossRefGoogle Scholar
  27. 27.
    Pascual J, Colas R, Castillo J. Epidemiology of chronic daily headache. Curr Pain Headache Rep. 2001;5(6):529–36.PubMedCrossRefGoogle Scholar
  28. 28.
    Rapoport A, Stang P, Gutterman DL, Cady R, Markley H, Weeks R, et al. Analgesic rebound headache in clinical practice: data from a physician survey. Headache. 1996;36(1):14–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Russell MB, Lundqvist C. Prevention and management of medication overuse headache. Curr Opin Neurol. 2012;25(3):290–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Piazza F, Chiappedi M, Maffioletti E, Galli F, Balottin U. Medication overuse headache in school-aged children: more common than expected? Headache. 2012;52(10):1506–10.Google Scholar
  31. 31.
    Saper JR, Hamel RL, Lake AE 3rd. Medication overuse headache (MOH) is a biobehavioural disorder. Cephalalgia. 2005;25(7):545–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Fuh JL, Wang SJ, Lu SR, Juang KD. Does medication overuse headache represent a behavior of dependence? Pain. 2005;119(1–3):49–55.PubMedCrossRefGoogle Scholar
  33. 33.
    Saper JR, Lake AE 3rd. Borderline personality disorder and the chronic headache patient: review and management recommendations. Headache. 2002;42(7):663–74.PubMedCrossRefGoogle Scholar
  34. 34.
    Srikiatkhachorn A, Puangniyom S, Govitrapong P. Plasticity of 5-HT serotonin receptor in patients with analgesic-induced transformed migraine. Headache. 1998;38(7):534–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Srikiatkhachorn A, Tarasub N, Govitrapong P. Effect of chronic analgesic exposure on the central serotonin system: a possible mechanism of analgesic abuse headache. Headache. 2000;40(5):343–50.PubMedCrossRefGoogle Scholar
  36. 36.
    Pini LA, Sandrini M, Vitale G. The antinociceptive action of paracetamol is associated with changes in the serotonergic system in the rat brain. Eur J Pharmacol. 1996;308(1):31–40.PubMedCrossRefGoogle Scholar
  37. 37.
    Bjorkman R. Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol: experimental studies in the rat. Acta Anaesthesiol Scand Suppl. 1995;103:1–44.PubMedGoogle Scholar
  38. 38.
    Supornsilpchai W, le Grand SM, Srikiatkhachorn A. Cortical hyperexcitability and mechanism of medication-overuse headache. Cephalalgia. 2010;30(9):1101–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Saper JR, Lake AE 3rd, Bain PA, Stillman MJ, Rothrock JF, Mathew NT, et al. A practice guide for continuous opioid therapy for refractory daily headache: patient selection, physician requirements, and treatment monitoring. Headache. 2010;50(7):1175–93.PubMedCrossRefGoogle Scholar
  40. 40.
    De Felice M, Porreca F. Opiate-induced persistent pronociceptive trigeminal neural adaptations: potential relevance to opiate-induced medication overuse headache. Cephalalgia. 2009;29(12):1277–84.PubMedCrossRefGoogle Scholar
  41. 41.
    Mao J. Opioid-induced abnormal pain sensitivity. Curr Pain Headache Rep. 2006;10(1):67–70.PubMedCrossRefGoogle Scholar
  42. 42.
    Watkins LR, Hutchinson MR, Johnston IN, Maier SF. Glia: novel counter-regulators of opioid analgesia. Trends Neurosci. 2005;28(12):661–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24(8):450–5.PubMedCrossRefGoogle Scholar
  44. 44.
    De Felice M, Ossipov MH, Wang R, Dussor G, Lai J, Meng ID, et al. Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers. Brain. 2010;133(Pt 8):2475–88.PubMedCrossRefGoogle Scholar
  45. 45.
    Fumal A, Laureys S, Di Clemente L, Boly M, Bohotin V, Vandenheede M, et al. Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine. Brain. 2006;129(Pt 2):543–50.PubMedGoogle Scholar
  46. 46.
    Jakubowski M, Levy D, Goor-Aryeh I, Collins B, Bajwa Z, Burstein R. Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache. 2005;45(7):850–61.PubMedCrossRefGoogle Scholar
  47. 47.
    Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804–14.PubMedCrossRefGoogle Scholar
  48. 48.
    Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ, et al. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007;27(7):814–23.PubMedCrossRefGoogle Scholar
  49. 49.
    Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47(2):170–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Rabe K, Pageler L, Gaul C, Lampl C, Kraya T, Foerderreuther S, et al. Prednisone for the treatment of withdrawal headache in patients with medication overuse headache: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2013;33(3):202–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Swidan SZ, Lake AE 3rd, Saper JR. Efficacy of intravenous diphenhydramine versus intravenous DHE-45 in the treatment of severe migraine headache. Curr Pain Headache Rep. 2005;9(1):65–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Silberstein SD, Schulman EA, Hopkins MM. Repetitive intravenous DHE in the treatment of refractory headache. Headache. 1990;30(6):334–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129–36.PubMedCrossRefGoogle Scholar
  54. 54.
    Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology. 1986;36(7):995–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Nagy AJ, Gandhi S, Bhola R, Goadsby PJ. Intravenous dihydroergotamine for inpatient management of refractory primary headaches. Neurology. 2011;77(20):1827–32.PubMedCrossRefGoogle Scholar
  56. 56.
    Bigal ME, Bordini CA, Speciali JG. Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial. J Emerg Med. 2002;23(2):141–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials. BMJ. 2004;329(7479):1369–73.PubMedCrossRefGoogle Scholar
  58. 58.
    Jones J, Sklar D, Dougherty J, White W. Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache. JAMA. 1989;261(8):1174–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Miner JR, Fish SJ, Smith SW, Biros MH. Droperidol vs. prochlorperazine for benign headaches in the emergency department. Acad Emerg Med. 2001;8(9):873–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Schwartz TH, Karpitskiy VV, Sohn RS. Intravenous valproate sodium in the treatment of daily headache. Headache. 2002;42(6):519–22.PubMedCrossRefGoogle Scholar
  61. 61.
    Mathew NT, Kailasam J, Meadors L, Chernyschev O, Gentry P. Intravenous valproate sodium (depacon) aborts migraine rapidly: a preliminary report. Headache. 2000;40(9):720–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Shrestha M, Singh R, Moreden J, Hayes JE. Ketorolac vs chlorpromazine in the treatment of acute migraine without aura: a prospective, randomized, double-blind trial. Arch Intern Med. 1996;156(15):1725–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Demirkaya S, Vural O, Dora B, Topcuoglu MA. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache. 2001;41(2):171–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Bigal ME, Bordini CA, Tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2002;22(5):345–53.PubMedCrossRefGoogle Scholar
  65. 65.
    Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate rapidly alleviates headaches of various types. Headache. 1996;36(3):154–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Donaldson D, Sundermann R, Jackson R, Bastani A. Intravenous dexamethasone vs placebo as adjunctive therapy to reduce the recurrence rate of acute migraine headaches: a multicenter, double-blinded, placebo-controlled randomized clinical trial. Am J Emerg Med. 2008;26(2):124–30.PubMedCrossRefGoogle Scholar
  67. 67.
    Fiesseler FW, Shih R, Szucs P, Silverman ME, Eskin B, Clement M, et al. Steroids for migraine headaches: a randomized double-blind, two-armed, placebo-controlled trial. J Emerg Med. 2011;40(4):463–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Munksgaard SB, Bendtsen L, Jensen RH. Detoxification of medication-overuse headache by a multidisciplinary treatment programme is highly effective: a comparison of two consecutive treatment methods in an open-label design. Cephalalgia. 2012;32(11):834–44.PubMedCrossRefGoogle Scholar
  69. 69.
    Creac’h C, Frappe P, Cancade M, Laurent B, Peyron R, Demarquay G, et al. In-patient versus out-patient withdrawal programmes for medication overuse headache: a 2-year randomized trial. Cephalalgia. 2011;31(11):1189–98.PubMedCrossRefGoogle Scholar
  70. 70.
    Lake AE 3rd, Saper JR, Hamel RL. Comprehensive inpatient treatment of refractory chronic daily headache. Headache. 2009;49(4):555–62.PubMedCrossRefGoogle Scholar
  71. 71.
    Zed PJ, Loewen PS, Robinson G. Medication-induced headache: overview and systematic review of therapeutic approaches. Ann Pharmacother. 1999;33(1):61–72.PubMedCrossRefGoogle Scholar
  72. 72.
    Hagen K, Albretsen C, Vilming ST, Salvesen R, Gronning M, Helde G, et al. A 4-year follow-up of patients with medication-overuse headache previously included in a randomized multicentre study. J Headache Pain. 2011;12(3):315–22.PubMedCrossRefGoogle Scholar
  73. 73.
    Rossi P, Faroni JV, Nappi G. Medication overuse headache: predictors and rates of relapse in migraine patients with low medical needs. A 1-year prospective study. Cephalalgia. 2008;28(11):1196–200.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Michigan Head Pain & Neurological InstituteAnn ArborUSA

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