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The Evolution of Medication Overuse Headache: History, Pathophysiology and Clinical Update

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Abstract

Medication overuse headache (MOH), the development or worsening of chronic headache resulting from frequent and excessive intake of medications used for acute treatment of headache, is a common secondary headache disorder and is associated with significant personal and societal burdens. The plausible physiologic mechanism is that chronic exposure to acute care migraine treatment leads to suppression of endogenous antinociceptive systems, consequently facilitating the trigeminal nociceptive process via up-regulation of the calcitonin gene-related peptide (CGRP) system. Recognizing and preventing its development is an integral aspect of migraine management, as medication overuse is a modifiable risk factor in the progression from episodic to chronic migraine. Over the years, MOH has been difficult to treat and has generated much controversy. Ongoing debates exist over the diagnostic criteria and treatment strategies, particularly regarding the roles of formal detoxification and preventive treatment. The arrival of the anti-CGRP monoclonal antibodies has also challenged our views of MOH and its treatment. This review outlines the evolution of MOH diagnostic criteria, presents the current understanding of MOH pathogenesis and discusses the debates over its development and treatment. Data on the efficacy of anti-CGRP monoclonal antibodies in the setting of medication overuse is also presented. These results indicate that patients with medication overuse, who are treated with these new medications, may not need to be detoxified in order to treat MOH. In light of these developments, it is likely that in the future MOH will be more readily diagnosed and treatment will result in better outcomes.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, St Vincent’s Hospital, University of Melbourne, Melbourne, Australia

    Christina Sun-Edelstein

  2. Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Alan M. Rapoport

  3. Department of Medicine, King Mongkut’s Institute of Technology Ladkrabang, Bangkok, Thailand

    Wanakorn Rattanawong

  4. Faculty of Medicine, King Mongkut’s Institute of Technology Ladkrabang, Bangkok, Thailand

    Anan Srikiatkhachorn

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  1. Christina Sun-Edelstein
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Correspondence to Christina Sun-Edelstein.

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Dr Sun-Edelstein is on the Migraine Advisory Boards for Teva, Eli Lilly, and Lundbeck. She has also received speaking fees from Teva and Eli Lilly. Compliance with Ethical Standards statement: “I am on the migraine advisory board for Teva, Eli Lilly, and Lundbeck pharmaceutical companies and have received speaking fees from Teva and Eli Lilly. Discussion of their medications in this manuscript is primarily based on data that has been published or presented at conferences. Any description of my experiences with these medications is clearly specified as such and is not influenced by any role I have with these companies.” Prof. Rapoport has received consulting fees or honoraria from Allergan, Amgen, Biohaven, Cala Health, Novartis, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc, and Zosano. He has also received speaking fees from Allergan, Amgen Biohaven, Lundbeck, and Teva Pharmaceutical Industries. Compliance with Ethical Standards statement: “I have consulted for and have been part of the Speakers Bureau for multiple companies. Any mention of clinical data from any of those companies is purely an accurate representation of that data. Any mention of how I use a medication is the honest representation of how I would use it whether or not I was a consultant or speaker for the company.” Dr Rattanawong does not have anything to disclose. Prof. Srikiatkhachorn does not have anything to disclose.

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Article conceptualization: AR, AS, CSE. Writing: Original draft preparation (CSE, AS), review and editing (AR, CSE, AS, WR).

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Sun-Edelstein, C., Rapoport, A.M., Rattanawong, W. et al. The Evolution of Medication Overuse Headache: History, Pathophysiology and Clinical Update. CNS Drugs 35, 545–565 (2021). https://doi.org/10.1007/s40263-021-00818-9

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