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Differential medication overuse risk of novel anti-migraine therapeutics

Research output: Contribution to journalArticlepeer-review

Chonlawan Saengjaroentham, Lauren C Strother, Isaac Dripps, Mohammad Rayhan Sultan Jabir, Amynah Pradhan, Peter J Goadsby, Philip R Holland

Original languageEnglish
Pages (from-to)2681-2688
Number of pages8
Issue number9
Early online date18 Aug 2020
Accepted/In press3 May 2020
E-pub ahead of print18 Aug 2020
Published1 Sep 2020

Bibliographical note

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.


King's Authors


Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use. The current study explores the potential medication overuse risk of two novel therapeutic drug classes, namely the ditans: 5-HT1F receptor agonists, and the gepants: calcitonin gene-related peptide receptor antagonists, in a preclinical model of medication overuse. Persistent exposure of mice to the 5-HT1F agonist LY344864, but not olcegepant produced a significant reduction in hind paw and orofacial mechanical withdrawal thresholds as a surrogate readout of allodynia. In agreement, only LY344864 induced neuroplastic changes in trigeminal sensory afferents, increasing calcitonin gene-related peptide expression and basal trigeminal nociception. Our data highlight a differential medication overuse headache risk profile for the ditan and gepant classes of drugs that has important implications for their clinical use and patient education to help reduce the burden of medication overuse headache.

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