Treating Hemicrania Continua When Indomethacin Can't Be Used

by Teri Robert Patient Advocate

Hemicrania continua is not a form of migraine. It's an entirely separate primary headache disorder. The International Headache Society's International Classification of Headache Disorders, 3rd edition (ICHD-3) describes hemicrania as:

"Persistent, strictly unilateral headache, associated with ipsilateral conjunctival injection (forcing of fluid into the conjuctiva, the mucous membrane that lines the eyelids), lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis and/or eyelid edema, and/or with restlessness or agitation. The headache is absolutely sensitive to indomethacin."


The Research Poster

Study Objectives:

"To find safe and comparable alternative treatments for HC in patients intolerant to indomethacin."


Study Background:

"Hemicrania continua (HC) is a primary headache disorder which responds absolutely to therapeutic doses of indomethacin. Unfortunately, approximately a fourth of patients develop adverse effects leading to discontinuation of the drug, and no other treatments have been proven to be consistently effective."


Study Methods:

  • The Mayo Clinic's medical index database was searched to include the period from January, 2004, to November, 2013.

  • Researchers performed a retrospective medical record review of HC patients seen by headache specialists at Mayo.

  • Patients who discontinued indomethacin due to intolerance were identified.

  • Alternative treatments tried were recorded for response rate, efficacy, and side effect profile, which were documented in subsequent visits and communications with headache specialists.

Study Results:

  • 291 patients with a possible diagnosis of HC were identified.

  • 41 were diagnosed with HC according to the International Classification of Headache Disorders 2nd edition (ICHD-II) by a headache specialist.

  • 12 patients discontinued indomethacin: 11 (26.8%) due to adverse outcomes, and one (2.4%) due to a diagnosis of non-alcoholic fatty liver disease (NAFLD).

  • The commonly reported adverse effects were gastrointestinal (63.6%), and elevated creatinine (18%).

  • Alternative treatments tried after the discontinuation of indomethacin included:

    • gabapentin (Neurontin),

    • melatonin,

    • verapamil,

    • topiramate (Topamax),

    • celecoxib (Celebrex),

    • and onabotulinumtoxinA (Botox).

  • Preventive treatment with these agents resulted in a partial decrease of headache severity but not frequency in 33% cases with gabapentin and 25% with both celecoxib and verapamil respectively.

  • No therapeutic response was reported with topiramate or melatonin.

  • Adverse side effects were reported in 66.7% cases with gabapentin, 25% with celecoxib, and 28.6% with topiramate.

  • No adverse outcomes were reported with verapamil or melatonin.

  • Six patients received onabotulinumtoxinA after alternative treatments had been tried and failed.

  • Favorable responses were reported with onabotulinumtoxinA in 5 cases (83%):

    • two became headache-free,

    • one reported a headache frequency decrease by 66%,

    • the other two reported an unquantified but meaningful decrease in headache severity but not in frequency.

    • One patient (16.6%) reported no benefit.

    • No adverse outcomes were reported with onabotulinumtoxinA.

Study Conclusion:

"Indomethacin is the most effective treatment for HC. Adverse effects and comorbidities which preclude the use of indomethacin often make the treatment of HC challenging. In clinical practice, alternative treatments have not been consistently effective or tolerated. In our series, onabotulinumtoxinA was well tolerated and superior to other alternatives commonly used in HC when indomethacin is not tolerated. Our findings suggest onabotulinumtoxinA may have an important role managing HC patients in whom indomethacin needs to be discontinued. In some cases, onabotulinumtoxinA may have comparable efficacy to indomethacin with a favorable side effect profile. Larger studies are needed to confirm our findings."


My Summary and Comments:

In a way, it would seem that hemicrania continua should be easy to treat given that one of the criteria for diagnosing it is that it responds to indomethacin. However, to the extreme frustration of both patients and their doctors, it's not that simple. Because of the potential side effects and various contraindications some due to comorbid conditions, many people cannot take indomethacin.

This is an issue that has needed to be studied for quite some time. The results of this study are promising. For onabotulinumtoxinA to have resulted in even two patients becoming headache-free is remarkable. Although reading the potential side effects of onabotulinumtoxinA can look somewhat alarming, it's important to note that its side effects profile is actually quite favorable when compared to that of many other treatments used for migraine and headache prevention. Hopefully, larger studies will be undertaken soon.


1 Musonza, T.; Garza, I.; Robertson, C.E. "Treatment of Hemicrania Continua in Patients Intolerant to Indomethacin." Poster Presentation. 56th Annual Scientific Meeting; American Headache Society. Los Angeles. June, 2014.

2 Headache Classification Committee of the International Headache Society. "The International Classification of Headache Disorders, 3rd edition (beta version)." Cephalalgia. July 2013 vol. 33 no. 9 629-808

Live well,

PurpleRibbonTiny Teri1

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Teri Robert
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Teri Robert

Teri Robert is a leading patient educator and advocate and the author of Living Well with Migraine Disease and Headaches. A co-founder of the Alliance for Headache Disorders Advocacy and the American Headache and Migraine Association, she received the National Headache Foundation's Patient Partners Award and a Distinguished Service Award from the American Headache Society.