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Harrison’s Online


A Long Course of Intravenous Dihydroergotamine Likely Effective for Refractory Headaches

S. Andrew Josephson
M.D., Department of Neurology, University of California San Francisco, San Francisco, USA

Patients with chronic headache disorders present a particularly difficult challenge for physicians aiming to relieve pain and prevent disability. For nearly three decades, IV dihydroergotamine (DHE) has been an option for treatment of refractory migraine in both emergency and inpatient settings. Nagy and colleagues (2011) examined a large series of cases using IV DHE for a variety of headache conditions and in a more prolonged dosing schedule in order to report a contemporary experience with this drug.

The authors retrospectively interviewed a subpopulation of 163 of the 446 patients treated with IV DHE over a 5-year period at a single institution in London. A total of 110 women and 52 men with an average age of 45 years were included. Diagnoses included chronic migraine in 114 (70%), cluster in 38 (23%), and new daily persistent headache in 11 (7%). One patient had both migraine with aura and new daily persistent headache. Patients were treated with an IV DHE inpatient protocol that included 5 days of treatment with a goal cumulative dosage of 11.25 mg (range, 8.25 €“11.25 mg). Severe nausea, a known side effect, was treated with a variety of antiemetic medications.

A total of 74% of the patients with migraine reported benefit, half of which was rated as moderate or excellent. A total of 67% reported headache freedom during treatment, and 75% percent achieved freedom within 1 month of therapy. The effect of this therapy on these patients with medically refractory migraine lasted an average of 28 days. All of the treated patients halted their medication overuse, including that of narcotics €”a primary reason why some have advocated admission for IV DHE therapy in the past. In terms of disability, 25% reported less time off work following treatment and 50% reported increased activity. Patients who had migraine with aura (n=42) had no appreciable differences in their results compared to those without aura.

A total of 84% of the patients with cluster headache reported headache freedom during the hospitalization for IV DHE treatment; the mean time to return of attacks was 17 days. Of the 11 patients with new daily persistent headache, only 2 (18%) reported a mild benefit with the treatment. In the entire cohort, the largest predictor of achieving a pain-free state in a logistic model was increasing DHE dose (p = .001); greater amounts of nausea despite treatment with antiemetics was a predictor of failure to become pain free (p = .002).

The most common adverse event was nausea, which was reported in 94 patients (58%) and led to cessation of IV DHE treatment in 6. Other common adverse events were leg cramps and the need for replacement of the peripheral IV. Other side effects included limb pain with infusion in 26 and chest tightness during the infusion in 5. No cardiac effects including electrocardiographic changes were found in the cohort.

This report certainly suffers from limitations inherent in a retrospective analysis of an uncontrolled study. However, a few important points emerge in this modern snapshot of DHE use that may be useful to clinicians. First, DHE is an effective therapy that can be considered in patients with refractory headache disorders including cluster headache. Interestingly, some of the patients achieved their pain-free state in a delayed fashion following discharge; this suggests that physicians should counsel their patients that the goal of IV DHE therapy is not to achieve a pain-free state during the actual admission but rather that some effects will be achieved only well after discharge and may be long-lasting. Nausea is a common side effect and, if not controlled aggressively, can lead to treatment failure. Finally, the successful response to a longer course and cumulative dose of DHE, often 5 days and 11.25 mg, should drive protocol changes in hospitals considering this treatment. For clinicians and their patients with refractory migraine or cluster headache, IV DHE should be considered, although the cost-benefit analysis of a potentially 5-day hospitalization is an extremely important consideration meriting future investigation.

– Josephson SA. A Long Course of Intravenous Dihydroergotamine Likely Effective for Refractory Headaches. Harrison’s Online, December 13, 2011. https://www.accessmedicine.com

Related to Chapter 14 Headache, in Harrison €™s Principles of Internal Medicine, 18th edition, Dan L. Longo, Dennis L. Kasper, J. Larry Jameson, Anthony S. Fauci, Stephen L. Hauser, Joseph Loscalzo, Eds. McGraw-Hill, New York, 2012.


Nagy AJ et al. Intravenous dihydroergotamine for inpatient management of refractory primary headaches. Neurology 2011;77:1827. [PubMed ® Abstract]

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