Double-Blind, Multicenter Trial to Compare the Efficacy of Intramuscular Dihydroergotamine Plus Hydroxyzine Versus Intramuscular Meperidine Plus Hydroxyzine for the Emergency Department Treatment of Acute Migraine Headache,☆☆,,★★

Presented at the Society for Academic Emergency Medicine Annual Meeting, San Francisco, CA, May 1993.
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Abstract

Study objective: To evaluate intramuscular dihydroergotamine in direct comparison with opioid analgesia in the treatment of acute migraine headache.

Methods: This was a prospective, multicenter, double-blind trial performed in the emergency departments of 11 general hospitals in the United States. One hundred seventy-one patients between the ages of 18 and 60 years who presented to the ED with acute migraine headache were enrolled. Patients were randomly assigned to receive either 1 mg dihydroergotamine (DHE) or 1.5 mg/kg meperidine (MEP) by intramuscular injection. The antinauseant hydroxyzine (H) was coadministered in both treatment groups.

Results: One hundred fifty-six patients were evaluable. Treatment groups were comparable in sample size, demographics, and baseline measurements of headache pain. Reduction of headache pain as measured on a 100-mm visual analog scale was 41±33 mm (53.5% reduction) for the DHE group, and 45±30 mm (55.7% reduction) for the MEP group at 60 minutes after treatment (difference=2.2%; 95% confidence interval [CI] –10%, 14.5%; P=.81). Reduction in the severity of nausea and improvement in functional ability were similar between treatment groups. Central nervous system adverse events were less common in the DHE group (DHE 23.5% versus MEP 37.6%, difference=–14.1%: 95% CI –28%, 0%). In particular, dizziness was reported less commonly with DHE than MEP (2% versus 15%, difference=–13%: 95% CI –21%, –5%).

Conclusion: In this prospective, double-blind trial of a convenience sample of ED patients randomly assigned to one of two treatment regimens, DHE and MEP were comparable therapies for acute migraine. The use of DHE avoids several problems associated with opioid analgesia, including dizziness.

[Carleton SC, Shesser RF, Pietrzak MP, Chudnofsky CR, Starkman S, Morris DL, Johnson G, Rhee KJ, Barton CW, Chelly JE, Rosenberg J, Van Valen, MK: Double-blind, multicenter trial to compare the efficacy of intramuscular dihydroergotamine plus hydroxyzine versus intramuscular meperidine plus hydroxyzine for the emergency department treatment of acute migraine headache. Ann Emerg Med August 1998;32:129-138.]

Section snippets

INTRODUCTION

There is no universally accepted, standard regimen for the abortive therapy of acute migraine headache. Opioid analgesics are commonly used in the emergency department treatment of migraine, and meperidine (MEP) has served as a reference drug in several comparative clinical trials for acute migraine.1, 2, 3, 4, 5, 6 The use of parenteral opioids in the ED is associated with several disadvantages relating to the encouragement of spurious presentations for drug seeking and difficulties with

Enrollment

Patients with a chief complaint of headache presenting to the EDs at 11 general hospitals (sites) from November 1991 to August 1992 were identified to study personnel by ED nursing staff, then approached and screened for enrollment. Screening and enrollment were not consecutive; patients presenting during times when study personnel were unavailable were not approached. Records were not kept on patients who were screened but refused enrollment. No steps were taken to relieve patients’ pain

Patient characteristics

One hundred seventy-one patients were enrolled and received at least 1 dose of either DHE or MEP. The intent-to-treat population consisted of 170 patients (85 in each group); 1 patient was excluded from the enrolled population because of complete loss of records. Fourteen patients (7 in each group) were excluded from the analysis of efficacy because of protocol violations. One of these patients was demonstrated after study enrollment to have meningitis that was considered to be unrelated to the

DISCUSSION

This trial was a randomized, controlled study of acute migraine headache treatment in a nonconsecutive convenience sample of ED patients. The study demonstrated that intramuscular DHE+H and MEP+H produce comparable reductions in migraine headache pain. DHE+H resulted in fewer CNS adverse events than the combination of MEP+H overall, and was significantly less likely to provoke dizziness as a complication of therapy. The current study used a dosage of the active control regimen, MEP, that was

Acknowledgements

We gratefully acknowledge the contributions to data analysis of the late Betty Margul, MD, of Novartis Pharmaceuticals Corporation. The authors also offer sincere thanks to the physicians, nurses, and ED personnel who assisted in the conduct of this study, and in particular to the following individuals: Catherine Hamilton, RN, MPH, University of Cincinnati; Sandra Sanford, RN, George Washington University; Thomas E Terndrup, MD, SUNY; and Rita A Manfredi, MD, Alexandria Hospital.

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    From the Department of Emergency Medicine, University Hospital of Cincinnati,* Cincinnati, OH; the Department of Emergency Medicine, George Washington University, Washington DC; Uniformed Services University of the Health Sciences, Bethesda, MD, and Andrews Air Force Base,§ MD; the Department of Emergency Medicine, University of Massachusetts, Worcester, MA; the UCLA Emergency Medicine Center, Los Angeles, CA; the Department of Emergency Medicine, University of North Carolina,# Chapel Hill, NC; the Department of Emergency Medicine, SUNY Health Sciences Center,** Syracuse, NY; the Division of Emergency Medicine and Toxicology, University of California, Davis,‡‡ Sacramento, CA; Emergency Medicine, University of California, San Francisco,§§ San Francisco, CA; the Department of Emergency Medicine, University of Texas, Houston,∥∥ Houston, TX; and Novartis Medical Operations,¶¶ East Hanover, NJ.

    ☆☆

    Supported by the Medical Operations Division of Novartis Pharmaceuticals Corporation, East Hanover, NJ.

    Reprint no.47/1/91462

    ★★

    Address for reprints: Steven C Carleton, MD, PhD Department of Emergency Medicine University of Cincinnati Hospital 231 Bethesda Avenue Cincinnati, OH 45267-0769 513-558-5281 Fax 513-558-5791 E-mail [email protected]

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