Repetitive dihydroergotamine nasal spray for treatment of refractory headaches:an open-label pilot study

ABSTRACT

Objective: To evaluate the safety and efficacy of a repetitive intranasal (IN) dihydroergotamine (DHE) burst protocol for treatment of refractory headaches.

Research design and methods: Patients with refractory headaches were enrolled in a prospective, open-label, pilot study. Patients were instructed to self-administer IN DHE every 8 hours for 3 days; each IN DHE dose consisted of one 0.5-mg spray in each nostril that was repeated 15 minutes later, for a total of 2.0 mg DHE per dose. Follow-up visits were scheduled approximately 3 weeks later.

Main outcome measures: Efficacy and safety measurements were collected during patient interviews. Primary efficacy measures were the change in headache frequency, duration, and severity (rated from 0 [none] to 5 [extremely severe]) between the initial and follow-up visits. Safety was assessed at the follow-up visits through the occurrence of adverse events (AEs).

Results: Twenty-six patients were enrolled in the study. Follow-up visits were completed by 24 patients whose mean headache frequency at study entry was 6.6 d/wk. The IN DHE burst protocol was associated with significant mean decreases in headache frequency (2.6 d/wk, p < 0.001), duration (5.8 hours, p = 0.03), and severity (1.2 units, p < 0.001) between study entry and the follow-up visit. One patient discontinued IN DHE use early because of an AE (nasal stuffiness); two additional patients each reported one AE (fatigue and increased headache) that was attributed to IN DHE.

Conclusions: The results of this pilot study suggest that the IN DHE burst protocol may be an effective and safe treatment for refractory headaches; interpretation of these results is limited by the open-label, uncontrolled design and the small number of patients. The development of a doubleblind, placebo-controlled study to further evaluate this treatment regimen is warranted.

Key words: :

• Dihydroergotamine
• Intranasal
• Raskin protocol
• Refractory headache

Notes

* Preliminary data from a limited number of patients in this study were the subject of posters presented at the 46th Annual Scientific Meeting of the American Headache Society, June 10–13, 2004, in Vancouver, British Columbia, Canada, and the 47th Annual Scientific Meeting of the American Headache Society, June 23–26, 2005, in Philadelphia, Pennsylvania, USA.