Neurology
Intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headaches: A prospective, randomized, double-blind trial,☆☆,,★★

https://doi.org/10.1067/mem.2003.195Get rights and content

Abstract

Study objectives: We compare the efficacy of intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headache. Methods: We performed a randomized, prospective, double-blind trial performed at a tertiary care military ED. Forty patients, aged 18 to 65 years, presenting with typical migraine symptoms were enrolled. Patients were randomized to receive either 10 mg of prochlorperazine or 500 mg of valproate intravenously over 2 minutes. Pain, nausea, and sedation were assessed by using a standard visual analog scale (VAS). Changes in VAS scores were compared between groups from baseline to end point by using a rank sum test, over time by using 2-way repeated-measures analysis of variance, and by requirement for rescue at 60 minutes by using the Fisher exact test. Results: Comparison of the change in median VAS scores over 60 minutes revealed that sodium valproate was significantly less effective than prochlorperazine in reducing pain or nausea (P <.001). Median improvements in VAS pain scores (binomial confidence intervals) were as follows: 64.5 mm (48.1 to 75.6 mm) for prochlorperazine versus 9 mm (-3 to 39.6 mm) for sodium valproate. Median improvements in VAS nausea scores were as follows: 35.5 mm (13.2 to 47.9 mm) for prochlorperazine versus 2 mm (−1.3 to 11 mm) for sodium valproate. There was no significant difference (P =.603) detected in the median changes in VAS scores for sedation: -4 mm (−29.9 to 8.6 mm) for prochlorperazine versus 0 mm (−6.6 to 6 mm) for sodium valproate. Comparison of the mean VAS time curves for pain and nausea also demonstrated a significant difference (both P <.001) but not for sedation (P =.232). In post hoc analysis, valproate failed to elicit significant improvement in pain or nausea scores over time, whereas prochlorperazine improved pain by 30 minutes (P <.001) and nausea by 15 minutes (P =.002). At the conclusion of the study, 15 (79%) of 19 patients receiving valproate required rescue treatment compared with 5 (25%) of 20 patients receiving prochlorperazine (P <.001). Conclusion: Prochlorperazine was statistically and clinically superior to sodium valproate for the treatment of the pain and nausea associated with acute migraine headaches. [Ann Emerg Med. 2003;41:847-853.]

Introduction

Migraine headache is a common presenting complaint to the emergency department. The management of these patients presents a therapeutic challenge in attempting to provide pain relief while minimizing time spent in the ED. Numerous therapies have been tried, including narcotics, antiemetics, phenothiazines, triptans, ergot alkaloids, and nonsteroidal anti-inflammatory drugs.1, 2, 3, 4, 5, 6, 7 Among these, intravenous prochlorperazine is one of the most common and has been shown to be superior to placebo in randomized clinical trials.1, 8 However, the efficacy of prochlorperazine might be limited because of its sedative and extrapyramidal effects.

Recently, there has been increasing interest in sodium valproate, an antiepileptic agent that has shown some usefulness in the prophylactic treatment of migraine headaches.9 Several case series have revealed significant improvement in patients treated with intravenous sodium valproate.10, 11, 12 In the only prospective randomized trial, sodium valproate demonstrated similar effectiveness as that provided by the combination of dihydroergotamine and metoclopramide in the treatment of acute migraine headaches.13

The purpose of the present study was to compare the efficacy of intravenous sodium valproate with that of prochlorperazine for the initial ED treatment of migraine headaches. Our null hypothesis was that there would be no difference in visual analog scale (VAS) scores for pain, nausea, or sedation between the 2 agents.

Section snippets

Materials and methods

This was a randomized, controlled, double-blind study to evaluate the efficacy of intravenous sodium valproate when compared with prochlorperazine for the ED treatment of acute migraine headaches. The medical center's institutional review board for protection of human subjects approved the study. Written informed consent was obtained from all participants.

The study was conducted in the ED of a tertiary care medical center that serves beneficiaries of active duty and retired military personnel

Results

Between January 2002 and August 2002, 40 patients were enrolled in the study. One patient was dropped from the sodium valproate group because the data were incorrectly collected with a verbal analog scale rather than a VAS. On this scale, the patient, a woman, demonstrated only minimal improvement in pain (8/10 to 7/10) and required rescue medication (Figure 1).

. Total number of patients enrolled in each study group.

Baseline data, including pain, nausea, sedation, age, and sex are represented in

Discussion

Migraine headache is a common presentation to the ED. Currently, there is no criterion standard for abortive treatment in the ED. The optimal therapy would work quickly and have no significant side effects so that patients can obtain relief from their symptoms and be able to be discharged from the ED in an expedited fashion. Because the cause of migraine headaches remains unknown, many different classifications of medicines have been tried with varying success.

Prochlorperazine, a phenothiazine,

Acknowledgements

Author contributions: SM, TF, and DAT conceived and designed the trial and obtained research funding. TF and DAT supervised the conduct of the trial and data collection. RHR provided statistical advice on study design, and both RHR and DAT analyzed the data. DAT drafted the manuscript, and all authors contributed substantially to its revision. DAT takes responsibility for the paper as a whole.

References (17)

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The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.

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Presented at the American College of Emergency Physicians Research Forum , Seattle, WA, October 2002.

The Chief, Bureau of Medicine and Surgery, Navy Department, Washington, DC, Clinical Investigation Program, sponsored this report (CIP No. S01-096), as required by NSHSBETHINST 6000.41A. This study was supported by a grant from the Clinical Investigations Department, Naval Medical Center San Diego.

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