Indomethacin-responsive Headaches—A Narrative Review

Maria Dolores Villar-Martínez MD; David Moreno-Ajona MD; Calvin Chan MBChB; Peter J. Goadsby MD, PhD


Headache. 2021;61(5):700-714. 

In This Article

Abstract and Introduction


Background: Indomethacin is a nonsteroidal anti-inflammatory drug whose mechanism of action in certain types of headache disorders remains unknown. The so-called indomethacin-responsive headache disorders consist of a group of conditions with a very different presentation that have a particularly good response to indomethacin. The response is so distinct as to be used in the definition of two: hemicrania continua and paroxysmal hemicrania.

Methods: This is a narrative literature review. PubMed and the Cochrane databases were used for the literature search.

Results: We review the main pharmacokinetic and pharmacodynamics properties of indomethacin useful for daily practice. The proposed mechanisms of action of indomethacin in the responsive headache disorders, including its effect on cerebral blood flow and intracranial pressure, with special attention to nitrergic mechanisms, are covered. The current evidence for its use in primary headache disorders, such as some trigeminal autonomic cephalalgias, cough, hypnic, exertional or sexual headache, and migraine will be covered, as well as its indication for secondary headaches, such as those of posttraumatic origin.

Conclusion: Increasing understanding of the mechanism(s) of action of indomethacin will enhance our understanding of the complex pathophysiology that might be shared by indomethacin-sensitive headache disorders.