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Medication Overuse and Medication Overuse Headache: Risk Factors, Comorbidities, Associated Burdens and Nonpharmacologic and Pharmacologic Treatment Approaches

  • Psychological and Behavioral Aspects of Headache and Pain (D Buse, Section Editor)
  • Published:
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Abstract

Purpose of Review

With a worldwide high disease burden, medication overuse headache (MOH) is an endemic and disabling neurological disorder. Because of the limitations of previous study designs, there are still debates and questions regarding the disease’s nature and treatment strategy. This review will discuss the following concepts; (1) recent progress in association between medication overuse (MO) and MOH; (2) the burden, risk factors and comorbidities of MOH; (3) evidence of treatment in patients with MOH.

Recent Findings

The causal relationship between MO and MOH has not been identified. Currently, the treatment policy is still mainly based on small clinical observations, some with highly specified patients. In addition to withdrawal and preventive treatment, some studies have provided evidence for nonpharmacological treatments.

Summary

Well-designed studies for specific treatment strategies with enough statistical power are warranted to make more relevant, better clinical decisions.

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References

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

  1. Peters GA, Horton BT. Headache: with special reference to the excessive use of ergotamine preparations and withdrawal effects. Proc Staff Meet Mayo Clin. 1951;26(9):153–61.

    CAS  PubMed  Google Scholar 

  2. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.

    Google Scholar 

  3. Westergaard ML, Hansen EH, Glümer C, Olesen J, Jensen RH. Definitions of medication-overuse headache in population-based studies and their implications on prevalence estimates: a systematic review. Cephalalgia. 2014;34(6):409–25.

    Article  PubMed  Google Scholar 

  4. Castillo J, Munoz P, Guitera V, Pascual J. Epidemiology of chronic daily headache in the general population. Headache. 1999;39(3):190–6.

    Article  CAS  PubMed  Google Scholar 

  5. Colás R, Muñoz P, Temprano R, Gómez C, Pascual J. Chronic daily headache with analgesic overuse: epidemiology and impact on quality of life. Neurology. 2004;62(8):1338–42.

    Article  PubMed  Google Scholar 

  6. Lantéri-Minet M, Auray JP, El Hasnaoui A, Dartigues JF, Duru G, Henry P, et al. Prevalence and description of chronic daily headache in the general population in France. Pain. 2003;102(1–2):143–9.

    Article  PubMed  Google Scholar 

  7. Lu SR1, Fuh JL, Chen WT, Juang KD, Wang SJ. Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome predictors. Cephalalgia. 2001;21(10):980–6.

    Article  CAS  PubMed  Google Scholar 

  8. Prencipe M, Casini AR, Ferretti C, Santini M, Pezzella F, Scaldaferri N, et al. Prevalence of headache in an elderly population: attack frequency, disability, and use of medication. J Neurol Neurosurg Psychiatry. 2001;70(3):377–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Scher AI, Stewart WF, Liberman J, Lipton RB. Prevalence of frequent headache in a population sample. Headache. 1998;38(7):497–506.

    Article  CAS  PubMed  Google Scholar 

  10. Wang SJ, Fuh JL, Lu SR, Liu CY, Hsu LC, Wang PN, et al. Chronic daily headache in Chinese elderly: prevalence, risk factors, and biannual follow-up. Neurology. 2000;54(2):314–9.

    Article  CAS  PubMed  Google Scholar 

  11. Lance F, Parkes C, Wilkinson M. Does analgesic abuse cause headaches de novo? Headache. 1988;28:61–2 Letter.

    Article  CAS  PubMed  Google Scholar 

  12. Bowdler I, Kilian J. The association between analgesic abuse and headache: coincidental or causal? Headache. 1988;28:494 Letter.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Scher AI, Rizzoli PB, Loder EW. Medication overuse headache: an entrenched idea in need of scrutiny. Neurology. 2017;89(12):1296–304 This article discussed the weakness of the study design in the evidence of the causal relationship between ‘medication overuse’ and ‘medication overuse headache’.

    Article  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. Manack A, Buse DC, Serrano D, Turkel CC, Lipton RB. Rates, predictors, and consequences of remission from chronic migraine to episodic migraine. Neurology. 2011;76(8):711–8.

    Article  CAS  PubMed  Google Scholar 

  18. Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology. 2008;71(22):1821–8.

    Article  CAS  PubMed  Google Scholar 

  19. Paemeleire K, Bahra A, Evers S, Matharu MS, Goadsby PJ. Medication-overuse headache in patients with cluster headache. Neurology. 2006;67(1):109–13.

    Article  CAS  PubMed  Google Scholar 

  20. Hagen K, Linde M, Steiner TJ, Stovner LJ, Zwart JA. Risk factors for medication-overuse headache: an 11-year follow-up study. The Nord-Trøndelag Health Studies Pain. 2012;153(1):56–61.

    PubMed  Google Scholar 

  21. Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J. Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain. 2000;86(1–2):133–8.

    Article  CAS  PubMed  Google Scholar 

  22. Cernuda-Morollón E, Larrosa D, Ramón C, Vega J, Martínez-Camblor P, Pascual J. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013;81(14):1191–6.

    Article  PubMed  CAS  Google Scholar 

  23. Munksgaard SB, Ertsey C, Frandsen E, Bendtsen L, Tekes K, Jensen RH. Circulating nociceptin and CGRP in medication-overuse headache. Acta Neurol Scand. 2018 Nov 20. https://doi.org/10.1111/ane.13053.

  24. Atasoy HT, Unal AE, Atasoy N, Emre U, Sumer M. Low income and education levels may cause medication overuse and chronicity in migraine patients. Headache. 2005;45(1):25–31.

    Article  PubMed  Google Scholar 

  25. Wiendels NJ, Knuistingh Neven A, Rosendaal FR, Spinhoven P, Zitman FG, Assendelft WJ, et al. Chronic frequent headache in the general population: prevalence and associated factors. Cephalalgia. 2006;26(12):1434–42.

    Article  CAS  PubMed  Google Scholar 

  26. Jonsson P, Hedenrud T, Linde M. Epidemiology of medication overuse headache in the general Swedish population. Cephalalgia. 2011;31(9):1015–22.

    Article  PubMed  Google Scholar 

  27. Raggi A, Grazzi L, Ayadi R, Leonardi M, Proietti A, Schiavolin S, et al. Clinical and psychosocial features of frequent relapsers (FR) among patients with chronic migraine and medication overuse. Neurol Sci. 2017;38(Suppl 1):169–71.

    Article  PubMed  Google Scholar 

  28. Cevoli S, Mochi M, Scapoli C, Marzocchi N, Pierangeli G, Pini LA, et al. A genetic association study of dopamine metabolism-related genes and chronic headache with drug abuse. Eur J Neurol. 2006;13(9):1009–13.

    Article  CAS  PubMed  Google Scholar 

  29. Di Lorenzo C, Coppola G, Currà A, Grieco G, Santorelli FM, Lepre 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. 2012;32(16):1189–97.

    Article  PubMed  Google Scholar 

  30. Di Lorenzo C, Di Lorenzo G, Sances G, Ghiotto N, Guaschino E, Grieco GS, et al. Drug consumption in medication overuse headache is influenced by brain-derived neurotrophic factor Val66Met polymorphism. J Headache Pain. 2009;10(5):349–55.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bottiroli S, Allena M, Sances G, De Icco R, Avenali M, Fadic R, et al. COMOESTAS Consortium. Psychological, clinical, and therapeutic predictors of the outcome of detoxification in a large clinical population of medication-overuse headache: a six-month follow-up of the COMOESTAS Project. Cephalalgia. 2018:333102418783317 This multicenter-based study in Europe demonstrated the risk factors to predict relapse in patients with medication overuse headache after a detoxification program.

  32. Zidverc-Trajkovic JJ, Pekmezovic T, Jovanovic Z, Pavlovic A, Mijajlovic M, Radojicic A, et al. Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: a prospective cohort study. Cephalalgia. 2018;38(2):265–73.

    Article  PubMed  Google Scholar 

  33. Cargnin S, Viana M, Ghiotto N, Bianchi M, Sances G, Tassorelli C, et al. Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy. Eur J Neurol. 2014;21(7):989–95.

    Article  CAS  PubMed  Google Scholar 

  34. Lampl C, Thomas H, Tassorelli C, Katsarava Z, Laínez JM, Lantéri-Minet M, et al. Headache, depression and anxiety: associations in the Eurolight project. J Headache Pain. 2016;17:59.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bendtsen L, Munksgaard S, Tassorelli C, Nappi G, Katsarava Z, Lainez M, et al. COMOESTAS Consortium. 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. 2014;34(6):426–33.

    Article  CAS  PubMed  Google Scholar 

  36. Kristoffersen ES, Straand J, Russell MB, Lundqvist C. Disability, anxiety and depression in patients with medication-overuse headache in primary care - the BIMOH study. Eur J Neurol. 2016;23(Suppl 1):28–35.

    Article  PubMed  Google Scholar 

  37. Sarchielli P, Corbelli I, Messina P, Cupini LM, Bernardi G, Bono G, et al. SAMOHA Study Group.Psychopathological comorbidities in medication-overuse headache: a multicentre clinical study. Eur J Neurol. 2016;23(1):85–91.

    Article  CAS  PubMed  Google Scholar 

  38. Curone M, Tullo V, Mea E, Proietti-Cecchini A, Peccarisi C, Bussone G. Psychopathological profile of patients with chronic migraine and medication overuse: study and findings in 50 cases. Neurol Sci. 2011;32(Suppl 1):S177–9.

    Article  PubMed  Google Scholar 

  39. Westergaard ML, Glümer C, Hansen EH, Jensen RH. Medication overuse, healthy lifestyle behaviour and stress in chronic headache: results from a population-based representative survey. Cephalalgia. 2016;36(1):15–28.

    Article  PubMed  Google Scholar 

  40. Mose LS, Pedersen SS, Debrabant B, Jensen RH, Gram B. The role of personality, disability and physical activity in the development of medication-overuse headache: a prospective observational study. J Headache Pain. 2018;19(1):39.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Saylor D, Steiner TJ. The global burden of headache. Semin Neurol. 2018;38(2):182–90.

    Article  PubMed  Google Scholar 

  42. Kristoffersen ES, Grande RB, Aaseth K, Russell MB, Lundqvist C. Medication-overuse headache detoxification reduces headache disability - the Akershus study of chronic headache. Eur J Neurol. 2018;25(9):1140–7.

    Article  CAS  PubMed  Google Scholar 

  43. Linde M, Gustavsson A, Stovner LJ, Steiner TJ, Barré J, Katsarava Z, et al. The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol. 2012;19(5):703–11.

    Article  CAS  PubMed  Google Scholar 

  44. Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication- overuse headache: a systematic review. Cephalalgia. 2016;36(4):371–86.

    Article  PubMed  Google Scholar 

  45. Negro A, Curto M, Lionetto L, Guerzoni S, Pini LA, Martelletti P. A critical evaluation on MOH current treatments. Curr Treat Options Neurol. 2017;19(9):32.

    Article  PubMed  Google Scholar 

  46. Kristoffersen ES, Straand J, Vetvik KG, Benth JŠ, Russell MB, Lundqvist C. Brief intervention for medication-overuse headache in primary care. J Neurol Neurosurg Psychiatry. 2015;86(5):505–12.

    Article  PubMed  Google Scholar 

  47. Corbelli I, Sarchielli P, Eusebi P, Cupini LM, Caproni S, Calabresi P, et al. Early management of patients with medication-overuse headache: results from a multicentre clinical study. Eur J Neurol. 2018;(8):25, 1027–1033 The study found a high percentage of patients with medication overuse headache who ‘self-detoxified’ after being informed of the risk of medication overuse.

  48. Grande RB, Aaseth K, Benth JS, Lundqvist C, Russell MB. Reduction in medication-overuse headache after short information: the Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129–37.

    Article  CAS  PubMed  Google Scholar 

  49. Hagen K, Albretsen C, Vilming ST, Salvesen R, Grønning M, Helde G, et al. Management of medication overuse headache: 1-year randomized multicenter open-label trial. Cephalalgia. 2009;29(2):221–32.

    Article  CAS  PubMed  Google Scholar 

  50. Rossi P, Faroni JV, Nappi G. Short-term effectiveness of simple advice as a withdrawal strategy in simple and complicated medication overuse headache. Eur J Neurol. 2011;18(3):396–401.

    Article  CAS  PubMed  Google Scholar 

  51. Zeeberg P, Olesen J, Jensen R. Probable medication overuse headache: the effect of a 2-month drug-free period. Neurology. 2006;66(12):1894–8.

    Article  PubMed  Google Scholar 

  52. Sarchielli P, Messina P, Cupini LM, Tedeschi G, Di Piero V, Livrea P, et al. Sodium valproate in migraine without aura and medication overuse headache: a randomized controlled trial. Eur Neuropsychopharmacol. 2014;24(8):1289–97.

    Article  CAS  PubMed  Google Scholar 

  53. Pijpers JA, Louter MA, de Bruin ME, van Zwet EW, Zitman FG, Ferrari MD, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122–30.

    Article  CAS  PubMed  Google Scholar 

  54. Carlsen LN, Munksgaard SB, Jensen RH, Bendtsen L. Complete detoxification is the most effective treatment of medication-overuse headache: a randomized controlled open-label trial. Cephalalgia. 2018;38(2):225–36.

    Article  PubMed  Google Scholar 

  55. Evers S, Jensen R. European Federation of Neurological Societies. Treatment of medication overuse headache--guideline of the EFNS headache panel. Eur J Neurol. 2011;18(9):1115–21.

    Article  CAS  PubMed  Google Scholar 

  56. Cevoli S, Giannini G, Favoni V, Terlizzi R, Sancisi E, Nicodemo M, et al. Treatment of withdrawal headache in patients with medication overuse headache: a pilot study. J Headache Pain. 2017;18(1):56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Dodick DW, Turkel CC, RE DG, Aurora SK, Silberstein SD, Lipton RB, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo controlled phases of the PREEMPT clinical program. Headache. 2010;50(6):921–36.

    Article  PubMed  Google Scholar 

  58. 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.

    Article  CAS  PubMed  Google Scholar 

  59. Silberstein SD, Blumenfeld AM, Cady RK, Turner IM, Lipton RB, Diener HC, 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. 2013;331(1–2):48–56.

    Article  CAS  PubMed  Google Scholar 

  60. 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.

    Article  PubMed  Google Scholar 

  61. 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.

    Article  PubMed  Google Scholar 

  62. Silberstein S, Lipton R, Dodick D, Freitag F, Mathew N, Brandes J, et al. Topiramate treatment of chronic migraine: a randomized, placebo controlled trial of quality of life and other efficacy measures. Headache. 2009;49(8):1153–62.

    Article  PubMed  Google Scholar 

  63. Grazzi L, Andrasik F, D’Amico D, Leone M, Usai S, Kass SJ, et al. Behavioral and pharmacologic treatment of transformed migraine with analgesic overuse: outcome at 3 years. Headache. 2002;42(6):483–90 This study shows evidence of the long-term effect of nonpharmacological treatment in medication overuse headache.

    Article  PubMed  Google Scholar 

  64. Grazzi L, Usai S, Prunesti A, Bussone G, Andrasik F. Behavioral plus pharmacological treatment versus pharmacological treatment only for chronic migraine with medication overuse after day-hospital withdrawal. Neurol Sci. 2009;30(Suppl 1):S117–9.

    Article  PubMed  Google Scholar 

  65. Kristoffersen ES, Straand J, Russell MB, Lundqvist C. Lasting improvement of medication-overuse headache after brief intervention - a long-term follow-up in primary care. Eur J Neurol. 2017;24(7):883–91 This study shows evidence of the long-term effect of nonpharmacological treatment in medication overuse headache.

    Article  CAS  PubMed  Google Scholar 

  66. Grazzi L, Sansone E, Raggi A, D’Amico D, De Giorgio A, Leonardi M, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Grazzi L, Raggi A, D’Amico D, Sansone E, Leonardi M, Andrasik F, Gucciardi A, Guido D, D’Andrea G. A prospective pilot study of the effect on catecholamines of mindfulness training vs pharmacological prophylaxis in patients with chronic migraine and medication overuse headache. Cephalalgia 2018 13:333102418801584. [Epub ahead of print].

  68. Vacca A, Gai A, Govone F, Rubino E, De Martino P, Gentile S, et al. Noninvasive vagal nerve stimulation in chronic migraine with medication overuse headache. Pain Med. 2018;19(12):2575–7.

    Article  PubMed  Google Scholar 

  69. Paemeleire K, Van Buyten JP, Van Buynder M, Alicino D, Van Maele G, Smet I, et al. Phenotype of patients responsive to occipital nerve stimulation for refractory head pain. Cephalalgia. 2010;30(6):662–73.

    CAS  PubMed  Google Scholar 

  70. Serra G, Marchioretto F. Occipital nerve stimulation for chronic migraine: a randomized trial. Pain Physician. 15(3):245–53.

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Funding

This study was supported in part by grants from Ministry of Health and Welfare, Taiwan (MOHW 107-TDU-B-211-123001, MOST106-2314-B-010-019-MY2, MOHW 108-TDU-B-211-133001), and Brain Research Center, National Yang-Ming University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.

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  1. School of Medicine, China Medical University, Taichung, Taiwan

    Ping-Kun Chen

  2. Department of Neurology, China Medical University Hospital, Taichung, Taiwan

    Ping-Kun Chen

  3. Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan

    Shuu-Jiun Wang

  4. Brain Research Center and School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Shuu-Jiun Wang

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Correspondence to Shuu-Jiun Wang.

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Ping-Kun Chen declares no conflict of interest. Dr. Wang reports personal fees from Eli-Lilly, personal fees from Daiichi-Sankyo, personal fees from Pfizer, Taiwan, personal fees from Bayer and personal fees from Eisai, all outside of the submitted work.

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Chen, PK., Wang, SJ. Medication Overuse and Medication Overuse Headache: Risk Factors, Comorbidities, Associated Burdens and Nonpharmacologic and Pharmacologic Treatment Approaches. Curr Pain Headache Rep 23, 60 (2019). https://doi.org/10.1007/s11916-019-0796-7

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