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Medication-overuse headache: risk factors, pathophysiology and management

  • Review Article
  • Published:

From Nature Reviews Neurology

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Key Points

  • Medication-overuse headache (MOH) — headache worsening attributed to overuse of attack-aborting medication — is common: its prevalence in the general population is 1%, and as high as 11–70% in people with chronic daily headache

  • Although overuse of any pain medication can result in MOH, some drugs carry an increased risk of the disorder; combination analgesics, opioids and triptans are the medications that are most commonly associated with MOH

  • Risk factors of MOH include female gender, psychiatric comorbidities, pre-existing pain and medication use, and lifestyle-related factors; identification and education of at-risk patients could help to prevent the development of the disorder

  • The pathophysiology of MOH is not completely understood, but headache seems to make the brain more susceptible to central sensitization; moreover, acute pain medications can interfere with neurotransmitter systems and thereby lead to MOH

  • The most common comorbidities of MOH are depression and anxiety, and up to 50% of patients with MOH show a dependence-type behaviour, such as tolerance or loss of control over pain medication use

  • Treatment includes patient counselling, initiation of prevention therapy and detoxification; in patients with psychiatric comorbidities, history of substance abuse and in patients overusing opioids, inpatient detoxification in a specialist headache centre is recommended

Abstract

Medication-overuse headache (MOH) is defined by the International Classification of Headache Disorders as a headache in patients with a pre-existing primary headache disorder that occurs on ≥15 days per month for >3 months, and is caused by overuse of medication intended for acute or symptomatic headache treatment. The prevalence of MOH in the general population is around 1%, but the condition is much more common in people with headache, in particular chronic migraine. The phenotype of the headache in MOH depends on the initial primary headache and the type of overused acute medication. In this Review, we will discuss the epidemiology, risk factors, pathophysiology, prevention and treatment of MOH. Treatment of MOH is performed in three steps: educating patients about the relationship between frequent intake of acute headache medication and MOH with the aim to reduce intake of acute medication; initiation of migraine prevention (such as topiramate or onabotulinumtoxin A in migraine) in patients who fail step 1; detoxification on an outpatient basis or in a day hospital or inpatient setting, depending on severity and comorbidities. The success rate of treatment is around 50–70%, although patients whose MOH is associated with opioid overuse have higher relapse rates. In all patients with MOH, relapse rates can be reduced by patient education and care in the follow-up period.

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Figure 1: Treatment algorithm in medication-overuse headache.

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References

  1. Paemeleire, K., Evers, S. & Goadsby, P. J. Medication-overuse headache in patients with cluster headache. Curr. Pain Headache Rep. 12, 122–127 (2008).

    Article  PubMed  Google Scholar 

  2. Bahra, A., Walsh, M., Menon, S. & Goadsby, P. J. Does chronic daily headache arise de novo in association with regular use of analgesics? Headache 43, 179–190 (2003).

    Article  PubMed  Google Scholar 

  3. Westergaard, M. L., Hansen, E. H., Glumer, C., Olesen, J. & Jensen, R. H. Definitions of medication-overuse headache in population-based studies and their implications on prevalence estimates: a systematic review. Cephalalgia 34, 409–425 (2014).

    Article  PubMed  Google Scholar 

  4. Peters, G. & Horton, B. Headache: with special reference to the excessive use of ergotamine preparations and withdrawal effects. Proc. Staff Meet. Mayo Clin. 26, 153–161 (1951).

    CAS  PubMed  Google Scholar 

  5. Dichgans, J. et al. Analgetika-induzierter Dauerkopfschmerz. Dtsch. Med. Wochenschr. 109, 369–373 (in German) (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Diener, H. C. & Wilkinson, M. (eds) Drug Induced Headache (Springer, 1988).

    Book  Google Scholar 

  7. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache classification committee of the international headache society. Cephalalgia 8 (Suppl. 7), 1–96 (1988).

  8. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia 24 (Suppl. 1), 9–160 (2004).

  9. Olesen, J. et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 26, 742–746 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33, 629–808 (2013).

  11. Bigal, M., Rapoport, A., Sheftell, F., Tepper, S. & Lipton, R. Transformed migraine and medication overuse in a tertiary headache centre — clinical characteristics and treatment outcomes. Cephalalgia 24, 483–490 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. Limmroth, V., Katsarava, Z., Fritsche, G., Przywara, S. & Diener, H. Features of medication overuse headache following overuse of different acute headache drugs. Neurology 59, 1011–1014 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Creac'h, C. et al. One or several types of triptan overuse headaches? Headache 49, 519–528 (2009).

    Article  PubMed  Google Scholar 

  14. Ayzenberg, I. et al. The prevalence of primary headache disorders in Russia: a countrywide survey. Cephalalgia 32, 373–381 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Shahbeigi, S. et al. Epidemiology of headaches in Tehran urban area: a population-based cross-sectional study in district 8, year 2010. Neurol. Sci. 34, 1157–1166 (2013).

    Article  PubMed  Google Scholar 

  16. Wang, S.-J. et al. Chronic daily headache in Chinese elderly. Prevalence, risk factors and biannual follow-up. Neurology 54, 314–319 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Prencipe, M. et al. Prevalence of headache in an elderly population: attack frequency, disability and use of medication. J. Neurol. Neurosurg. Psychiatry 70, 377–381 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dyb, G., Holmen, T. L. & Zwart, J. A. Analgesic overuse among adolescents with headache: the Head-HUNT-Youth Study. Neurology 66, 198–201 (2006).

    Article  PubMed  Google Scholar 

  19. Wang, S. J., Fuh, J. L., Lu, S. R. & Juang, K. D. Chronic daily headache in adolescents: prevalence, impact, and medication overuse. Neurology 66, 193–197 (2006).

    Article  PubMed  Google Scholar 

  20. Westergaard, M. L., Glumer, C., Hansen, E. H. & Jensen, R. H. Prevalence of chronic headache with and without medication overuse: associations with socioeconomic position and physical and mental health status. Pain 155, 2005–2013 (2014).

    Article  PubMed  Google Scholar 

  21. Hagen, K., Linde, M., Steiner, T. J., Stovner, L. J. & Zwart, J. A. Risk factors for medication-overuse headache: an 11-year follow-up study. The Nord-Trondelag Health Studies. Pain 153, 56–61 (2012).

    Article  PubMed  Google Scholar 

  22. Shand, B. et al. Clinical and demographical characteristics of patients with medication overuse headache in argentina and chile: analysis of the latin american section of COMOESTAS project. J. Headache Pain 16, 83 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hoem Nordhaug, L. et al. Headaches in patients with previous head injuries: a population-based historical cohort study (HUNT). Cephalalgia http://dx.doi.org/10.1177/0333102415618948 (2015).

  24. Heyer, G. L. & Idris, S. A. Does analgesic overuse contribute to chronic post-traumatic headaches in adolescent concussion patients? Pediatr. Neurol. 50, 464–468 (2014).

    Article  PubMed  Google Scholar 

  25. Knackstedt, H. et al. Cervicogenic headache in the general population: the Akershus study of chronic headache. Cephalalgia 30, 1468–1476 (2010).

    Article  PubMed  Google Scholar 

  26. Paemeleire, K., Bahra, A., Evers, S., Matharu, M. S. & Goadsby, P. J. Medication-overuse headache in patients with cluster headache. Neurology 67, 109–113 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Radat, F. et al. Psychiatric comorbidity in the evolution from migraine to medication overuse headache. Cephalalgia 25, 519–522 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Atasoy, H. T., Atasoy, N., Unal, A. E., Emre, U. & Sumer, M. Psychiatric comorbidity in medication overuse headache patients with pre-existing headache type of episodic tension-type headache. Eur. J. Pain 9, 285–291 (2005).

    Article  PubMed  Google Scholar 

  29. Radat, F. et al. Behavioral dependence in patients with medication overuse headache: a cross-sectional study in consulting patients using the DSM-IV criteria. Headache 48, 1026–1036 (2008).

    Article  PubMed  Google Scholar 

  30. Lundqvist, C., Aaseth, K., Grande, R. B., Benth, J. S. & Russell, M. B. The severity of dependence score correlates with medication overuse in persons with secondary chronic headaches. The Akershus study of chronic headache. Pain 148, 487–491 (2010).

    Article  PubMed  Google Scholar 

  31. Corbelli, I., Caproni, S., Eusebi, P. & Sarchielli, P. Drug-dependence behaviour and outcome of medication-overuse headache after treatment. J. Headache Pain 13, 653–660 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Scher, A. I., Lipton, R. B., Stewart, W. F. & Bigal, M. Patterns of medication use by chronic and episodic headache sufferers in the general population: results from the frequent headache epidemiology study. Cephalalgia 30, 321–328 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Lance, F., Parkes, C. & Wilkinson, M. Does analgesic abuse cause headaches de novo. Headache 28, 61–62 (1988).

    Article  CAS  PubMed  Google Scholar 

  34. Di Lorenzo, C. et al. Cortical response to somatosensory stimulation in medication overuse headache patients is influenced by angiotensin converting enzyme (ACE) I/D genetic polymorphism. Cephalalgia 32, 1189–1197 (2012).

    Article  PubMed  Google Scholar 

  35. Phillips, M. I. Functions of angiotensin in the central nervous system. Annu. Rev. Physiol. 49, 413–435 (1987).

    Article  CAS  PubMed  Google Scholar 

  36. Pan, H. L. Brain angiotensin II and synaptic transmission. Neuroscientist 10, 422–431 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Binder, D. K., & Scharfman, H. E. Brain-derived neurotrophic factor. Growth Factors 22, 123–131 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gratacos, M. et al. 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, 911–922 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Bath, K. G. & Lee, F. S. Variant BDNF (Val66Met) impact on brain structure and function. Cogn. Affect. Behav. Neurosci. 6, 79–85 (2006).

    Article  PubMed  Google Scholar 

  40. Di Lorenzo, C. et al. Drug consumption in medication overuse headache is influenced by brain-derived neurotrophic factor Val66Met polymorphism. J. Headache Pain 10, 349–355 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Andersen, S. & Skorpen, F. Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics 10, 669–684 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Cargnin, S. et al. Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy. Eur. J. Neurol. 21, 989–995 (2014).

    Article  CAS  PubMed  Google Scholar 

  43. Serretti, A., Calati, R., Mandelli, L. & De Ronchi, D. Serotonin transporter gene variants and behavior: a comprehensive review. Curr. Drug Targets. 7, 1659–1669 (2006).

    Article  CAS  PubMed  Google Scholar 

  44. Kumar et al. Serotonin transporter gene (SLC6A4) polymorphism in patients with irritable bowel syndrome and healthy controls. J. Gastrointestin. Liver Dis. 21, 31–38 (2012).

    PubMed  Google Scholar 

  45. De Felice, M. et al. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann. Neurol. 67, 325–337 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Srikiatkhachorn, A., Tarasub, N. & Govitrapong, P. Effect of chronic analgesic exposure on the central serotonin system: a possible mechanism of analgesic abuse headache. Headache 40, 343–350 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Supornsilpchai, W., le Grand, S. M. & Srikiatkhachorn, A. Involvement of pro-nociceptive 5-HT2A receptor in the pathogenesis of medication-overuse headache. Headache 50, 185–197 (2010).

    Article  PubMed  Google Scholar 

  48. Dobson, C. F., T. Y., Diksic, M. & Hamel, E. Effects of acute or chronic administration of anti-migraine drugs sumatriptan and zolmitriptan on serotonin synthesis in the rat brain. Cephalalgia 24, 2–11 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Reuter, U., Salomone, S., Ickenstein, G. & Waeber, C. Effects of chronic sumatriptan and zolmitriptan treatment on 5-HT receptor expression and function in rats. Cephalalgia 24, 398–407 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Srikiatkhachorn, A. & Anthony, M. Serotonin receptor adaptation in patients with analgesic-induced headache. Cephalalgia 16, 419–422 (1996).

    Article  CAS  PubMed  Google Scholar 

  51. Srikiatkhachorn, A. & Anthony, M. Platelet serotonin in patients with analgesic-induced headache. Cephalalgia 16, 423–426 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Srikiatkhachorn, A., Puangniyom, S. & Govitrapong, P. Plasticity of 5-HT serotonin receptor in patients with analgesic-induced transformed migraine. Headache 38, 534–539 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Rossi, C., Pini, L. A., Cupini, M. L., Calabresi, P. & Sarchielli, P. Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: relation with serotonin levels. Eur. J. Clin. Pharmacol. 64, 1–8 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Cupini, L. M. et al. Degradation of endocannabinoids in chronic migraine and medication overuse headache. Neurobiol. Dis. 30, 186–189 (2008).

    Article  CAS  PubMed  Google Scholar 

  55. Loder, E. Post-marketing experience with an opioid nasal spray for migraine: lessons for the future. Cephalalgia 26, 89–97 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Ayzenberg, I. et al. Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures. Cephalalgia 26, 1106–1114 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Perrotta, A. et al. Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control. Cephalalgia 30, 272–284 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Coppola, G. et al. Abnormal cortical responses to somatosensory stimulation in medication-overuse headache. BMC Neurol. http://dx.doi.org/10.1186/1471-2377-10-126 (2010).

  59. Ferraro, D. et al. Habituation to pain in “medication overuse headache”: a CO2 laser-evoked potential study. Headache 52, 792–807 (2012).

    Article  PubMed  Google Scholar 

  60. Fuh, J. L., Wang, S. J., Lu, S. R. & Juang, K. D. Does medication overuse headache represent a behavior of dependence? Pain 119, 49–55 (2005).

    Article  PubMed  Google Scholar 

  61. Riederer, F. et al. Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety. World J. Biol. Psychiatry 13, 517–525 (2012).

    Article  PubMed  Google Scholar 

  62. Riederer, F. et al. Decrease of gray matter volume in the midbrain is associated with treatment response in medication-overuse headache: possible influence of orbitofrontal cortex. J. Neurosci. 33, 15343–15349 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Grazzi, L. et al. Chronic migraine with medication overuse pre-post withdrawal of symptomatic medication: clinical results and FMRI correlations. Headache 50, 998–1004 (2010).

    Article  PubMed  Google Scholar 

  64. Ferraro, S. et al. Pain processing in medication overuse headache: a functional magnetic resonance imaging (fMRI) study. Pain Med. 13, 255–262 (2012).

    Article  PubMed  Google Scholar 

  65. Ferraro, S. et al. In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas. Headache 52, 1520–1534 (2012).

    Article  PubMed  Google Scholar 

  66. Fumal, A. et al. Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine. Brain 129, 543–550 (2006).

    Article  PubMed  Google Scholar 

  67. Lai, T. H. et al. Gray matter changes related to medication overuse in patients with chronic migraine. Cephalalgia http://dx.doi.org/10.1177/0333102416630593 (2016).

  68. Hu, W., Guo, J., Chen, N., Guo, J. & He, L. A meta-analysis of voxel-based morphometric studies on migraine. Int. J. Clin. Exp. Med. 8, 4311–4319 (2015).

    PubMed  PubMed Central  Google Scholar 

  69. Sinding, C. et al. Grey matter changes of the pain matrix in patients with burning mouth syndrome. Eur. J. Neurosci. 43, 997–1005 (2016).

    Article  PubMed  Google Scholar 

  70. Diaz-Piedra, C., Guzman, M. A., Buela-Casal, G. & Catena, A. The impact of fibromyalgia symptoms on brain morphometry. Brain Imag. Behav. http://dx.doi.org/10.1007/s11682-015-9485-2 (2015).

  71. Fritz, H. et al. Chronic back pain is associated with decreased prefrontal and anterior insular gray matter: results from a population-based cohort study. J. Pain 17, 111–118 (2016).

    Article  PubMed  Google Scholar 

  72. Hedenrud, T., Babic, N. & Jonsson, P. Medication overuse headache: self-perceived and actual knowledge among pharmacy staff. Headache 54, 1019–1025 (2014).

    Article  PubMed  Google Scholar 

  73. Lanteri-Minet, M., Valade, D., Geraud, G., Lucas, C. & Donnet, A. Revised French guidelines for the diagnosis and management of migraine in adults and children. J. Headache Pain 15, 2 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Silberstein, S. D. et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 78, 1337–1345 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Pringsheim, T. et al. Canadian Headache Society guideline for migraine prophylaxis. Can. J. Neurol. Sci. 39, S1–S59 (2012).

    Article  PubMed  Google Scholar 

  76. Sarchielli, P. et al. Psychopathological comorbidities in medication-overuse headache: a multicentre clinical study. Eur. J. Neurol. http://dx.doi.org/10.1111/ene.12794 (2015).

  77. Fritsche, G. et al. Prevention of medication overuse in patients with migraine. Pain 151, 404–413 (2010).

    Article  PubMed  Google Scholar 

  78. Rossi, P., Di Lorenzo, C., Faroni, J., Cesarino, F. & Nappi, G. Advice alone versus structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia 26, 1097–1105 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Rossi, P., Faroni, J. V., Tassorelli, C. & Nappi, G. Advice alone versus structured detoxification programmes for complicated medication overuse headache (MOH): a prospective, randomized, open-label trial. J. Headache Pain 14, 10 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Grande, R. B., Aaseth, K., Benth, J. S., Lundqvist, C. & Russell, M. B. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur. J. Neurol. 18, 129–137 (2011).

    Article  CAS  PubMed  Google Scholar 

  81. Kristoffersen, E. S., Straand, J., Russell, M. B. & Lundqvist, C. Disability, anxiety and depression in patients with medication-overuse headache in primary care - the BIMOH study. Eur. J. Neurol. 23 (Suppl. 1), 28–35 (2016).

    Article  PubMed  Google Scholar 

  82. Diener, H. C. et al. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 27, 814–823 (2007).

    Article  PubMed  Google Scholar 

  83. Silberstein, S. D. et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 47, 170–180 (2007).

    Article  PubMed  Google Scholar 

  84. Silberstein, S. et al. Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures. Headache 49, 1153–1162 (2009).

    Article  PubMed  Google Scholar 

  85. Diener, H. C. et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia 29, 1021–1027 (2009).

    Article  PubMed  Google Scholar 

  86. Aurora, S. K. et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 30, 793–803 (2010).

    Article  CAS  PubMed  Google Scholar 

  87. Diener, H. C. et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 30, 804–814 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Dodick, D. W. et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 50, 921–936 (2010).

    Article  PubMed  Google Scholar 

  89. Silberstein, S. D. et al. OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. J. Neurol. Sci. 331, 48–56 (2013).

    Article  CAS  PubMed  Google Scholar 

  90. Chiang, C. C., Schwedt, T. J., Wang, S. J. & Dodick, D. W. Treatment of medication-overuse headache: a systematic review. Cephalalgia 36, 371–386 (2015).

    Article  PubMed  Google Scholar 

  91. Diener, H. C. & Limmroth, V. Medication-overuse headache: a worldwide problem. Lancet Neurol. 3, 475–483 (2004).

    Article  PubMed  Google Scholar 

  92. Katsarava, Z., Fritsche, G., Muessig, M., Diener, H. C. & Limmroth, V. Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 57, 1694–1698 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. Rabe, K. et al. Prednisone for the treatment of withdrawal headache in patients with medication overuse headache: a randomized, double-blind, placebo-controlled study. Cephalalgia 33, 202–207 (2013).

    Article  PubMed  Google Scholar 

  94. Boe, M. G., Mygland, A. & Salvesen, R. Prednisolone does not reduce withdrawal headache: a randomized, double-blind study. Neurology 69, 26–31 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Tassorelli, C. et al. A consensus protocol for the management of medication-overuse headache: evaluation in a multicentric, multinational study. Cephalalgia 34, 645–655 (2014).

    Article  PubMed  Google Scholar 

  96. Bendtsen, L. et al. Disability, anxiety and depression associated with medication-overuse headache can be considerably reduced by detoxification and prophylactic treatment. Results from a multicentre, multinational study (COMOESTAS project). Cephalalgia 34, 426–433 (2014).

    Article  CAS  PubMed  Google Scholar 

  97. Hagen, K. et al. Management of medication overuse headache: 1-year randomized multicentre open-label trial. Cephalalgia 29, 221–232 (2009).

    Article  CAS  PubMed  Google Scholar 

  98. Zeeberg, P., Olesen, J. & Jensen, R. Probable medication-overuse headache: the effect of a 2-month drug-free period. Neurology 66, 1894–1898 (2006).

    Article  PubMed  Google Scholar 

  99. Gaul, C., Bromstrup, J., Fritsche, G., Diener, H. C. & Katsarava, Z. Evaluating integrated headache care: a one-year follow-up observational study in patients treated at the Essen headache centre. BMC Neurol. 11, 124 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Gaul, C., Liesering-Latta, E., Schafer, B., Fritsche, G. & Holle, D. Integrated multidisciplinary care of headache disorders: a narrative review. Cephalalgia http://dx.doi.org/10.1177/0333102415617413 (2015).

  101. He, Z. et al. Metabolic syndrome in female migraine patients is associated with medication overuse headache: a clinic-based study in China. Eur. J. Neurol. 22, 1228–1234 (2015).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

H.-C.D. acknowledges the support of the German Research Foundation (Deutsche Forschungsgemeinschaft), Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) and the European Union.

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Authors and Affiliations

  1. Department of Neurology and Headache Center, University Hospital Essen, Hufelandstrasse 55, Essen, 45147, Germany

    Hans-Christoph Diener, Dagny Holle, Kasja Solbach & Charly Gaul

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Contributions

H.C.D. drafted the structure of the Review and was the main contributor to Introduction, treatment and prevention of medication overuse headache (MOH), as well as to the section on practical recommendations. K.S. was the main contributor to the section on definition of MOH. D.H. was the main contributor to the section on pathophysiology, and C.G. was the main contributor to the sections on epidemiology and predictors.

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Correspondence to Hans-Christoph Diener.

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Competing interests

H.-C.D. has received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Böhringer Ingelheim, Bristol-Myers Squibb, Chordate, Coherex, CoLucid, ElectroCore Medical, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Labrys Biologicals, Lilly, La Roche, 3M Medica, Medtronic, Menerini, Minster, MSD, Neuroscore, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, Sanofi, St. Jude Medical, Teva and Weber & Weber. Financial support for research projects was provided by Allergan, Almirall, AstraZeneca, Bayer, Electrocore Medical, GSK, Janssen-Cilag, MSD and Pfizer. He has no ownership interest and does not own stocks of any pharmaceutical company. D.H. has received financial support for research projects from Allergan, Grünenthal, Lilly, and research support from EFIC. K.S. has received honoraria for oral presentation from Allergan and MSD. C.G. has received honoraria from Allergan, Berlin-Chemie, MSD, ElectroCore Medical, St. Jude Medical, Grünenthal, Desitin, Bayer, Böhringer Ingelheim, Autonomic Technologies and Hormosan. He has no ownership interests and does not own any pharmaceutical company stocks.

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Diener, HC., Holle, D., Solbach, K. et al. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol 12, 575–583 (2016). https://doi.org/10.1038/nrneurol.2016.124

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  • DOI: https://doi.org/10.1038/nrneurol.2016.124

  • Springer Nature Limited

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