Parenteral diphenhydramine is commonly used as adjuvant therapy for acute migraine despite
the fact that data supporting this practice do not exist. The investigators propose a
randomized double blind study to test the hypothesis that 50mg of intravenous
diphenhydramine, when added to standard migraine therapy, will result in a greater rate of
sustained headache relief than standard migraine therapy alone. For this study, standard
migraine therapy will be 10mg of intravenous metoclopramide. Sustained headache relief is
defined as achieving a headache level of "mild" or "none" within two hours and maintaining a
level of "mild" or "none" for 48 hours. Patients who present to the Montefiore emergency room
(Bronx, NY) with an acute migraine will be approached for participation. They will be
screened for medication contra-indications and non-migraine etiologies of headache. The study
will be randomized. Assignment will be concealed. Participants and researchers will be
blinded. Efficacy outcomes and adverse events will be assessed every half hour for two hours
in the Emergency Department and by telephone 48 hours after medication administration. A
sample size calculation, based on pilot data, revealed the need for 374 participants. An
interim analysis will be performed after 200 participants have been enrolled with the goal of
assessing for lack of conditional power.