Side effects are the main culprit for treatment discontinuation in indomethacin-sensitive headache disorders

According to a real-world analysis, indomethacin-sensitive disorders such as hemicrania continua and paroxysmal hemicrania derive long-term benefit from indomethacin, with the most common reason for discontinuation being driven by side effects.

Dr Mantas Jokubaitis (King’s College London, UK) and colleagues assessed patients who were referred to 2 tertiary headache clinics (King’s College London and Leeds Teaching Hospitals) between January 2014 and October 2024 [1]. They focused on patients who received indomethacin treatment, to identify those with hemicrania continua and paroxysmal hemicrania. Data analysed for these patients included treatment effectiveness, safety and tolerability, duration of therapy, association with other headache disorders, and use of therapies other than indomethacin.

Of 4,099 clinical letters which contained the word “indomethacin”, the researchers selected 165 for analysis, including 87 diagnoses of hemicrania continua and 54 diagnoses of paroxysmal hemicrania. Around 70% of the included patients were women, and the median age was 46 years. In total, 130 patients had a follow-up of 5 years or longer. Indomethacin treatment was discontinued in 29.7% of patients included in the analysis. The major reason for discontinuation was the occurrence of adverse effects (36% gastrointestinal adverse effects and 25% CNS-related disorders such as dizziness or worsening headache). Other therapies in the study population included melatonin (n=43), greater occipital nerve blocks (n=39), non-invasive vagus nerve stimulation (n=39), and anti-CGRP monoclonal antibodies (n=12). Responses to these therapies were 40%, 63%, 51%, and 25%, respectively. Response to anti-CGRP monoclonal antibodies was associated with comorbid migraine (P<0.001) and patients receiving anti-CGRP antibodies tended to receive higher indomethacin doses (P=0.017)

The authors concluded that in this patient population with headache disorders treated with indomethacin, “long-term discontinuation was primarily driven by side effects”. Furthermore, CGRP-targeted therapies “independently predicted the use of indomethacin and were associated with comorbid migraine. The data suggests a potential synergistic mechanism in indomethacin-sensitive headaches with CGRP in some patients.”

1. Jokubaitis M, et al. Indomethacin-responsive headache disorders: long-term outcome on efficacy, tolerability, and treatment alternatives. 18^th European Headache Congress, 4–7 December 2024, Rotterdam, the Netherlands.

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Posted on 6 January 20256 January 2025