WASHINGTON – Intravenous diphenhydramine is not an effective adjuvant therapy for the treatment of acute migraine, according to a study presented by Dr. Ben Friedman at the annual meeting of the American Headache Society.
Dr. Friedman of the department of emergency medicine at Albert Einstein College of Medicine in New York explained that no high-quality evidence exists to support or refute the role of antihistamines in the treatment of acute migraine. Therefore, the purpose of Dr. Friedman’s investigation was to confirm that acute migraine, of either moderate or severe intensity, can be effectively treated by a combination of diphenhydramine 50 mg IV plus metoclopramide 10 mg IV, rather than a placebo and metoclopramide 10 mg IV.
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All subjects were no older than 65 years and presented to an emergency department with acute or severe migraine, or had probable migraine without aura – International Classification of Headache Disorders, 2nd edition, diagnoses 1.1 and 1.6.1, respectively – in the previous year. Patients were excluded if they had a history of allergy, a contraindication, intolerance of medications in the trial, or suspicion of secondary headache.
In total, 420 patients were deemed eligible for inclusion and 208 ultimately consented; they were randomized into either the placebo or diphenhydramine arm, and followed for 21 months starting in April 2013. The primary outcome was defined as achieving a mild headache, or no headache at all, within 2 hours of receiving medication and maintaining that level for at least 48 hours. The secondary outcome was an average improvement in the 0-10 numerical migraine rating scale within 1 hour of taking medication.
The results between the two cohorts, however, were not significantly different, and the study was halted for futility by a data safety monitoring committee at a planned interim analysis because of the lack of effect of diphenhydramine. Of patients randomized to diphenhydramine, 40% reported sustained relief, compared with 37% of patients randomized to placebo. One hour after medication administration, those randomized to diphenhydramine improved by a mean of 5.1 on a 0-10 scale, versus 4.8 for those randomized to placebo. Overall, 85% of the patients in the diphenhydramine arm reported they would want the same medication combination during a subsequent ED visit, as did 76% of those who received placebo. The length of stay in emergency departments – 122 minutes for patients who took diphenhydramine versus 131 minutes for those who took placebo – and the rates of side effects were also not significantly different between the two cohorts.
Eighty-five percent of the diphenhydramine group (88/104) were females, while 89% (92/104) were female in the placebo group. The average age was 34 years versus 36 years, while 64% (66 of 104) and 65% (67 of 104) were taking some form of medication before coming to the emergency department, respectively. Both cohorts reported a mean of 3 headache days per subject at baseline.
Although the study was conducted at just a single center (Montefiore Medical Center) within an underserved population, the results of the study clearly show that “there is no reason to administer [intravenous] diphenhydramine routinely for patients who present with acute or severe migraine,” Dr. Friedman said.
He did not report any relevant financial disclosures.