There is mounting evidence in favor of effectively treating migraine headaches with antiemetic dopamine antagonists such as metoclopramide (Reglan) and prochlorperazine (Compazine) as primary parenteral management.
Diphenhydramine (Benadryl) can be administered simultaneously with such agents to prevent akathisia and dystonic reactions.
Apart from the prophylactic effects of diphenhydramine, it may also play a synergistic role is actually treating the symptoms.
A recent study (Friedman, et al) showed no significant difference in the efficacy or adverse events of treating migraine with 20 mg of metoclopramide plus 25 mg of diphenhydramine versus 10 mg of prochlorperazine plus 25 mg of diphenhydramine, although there was an insignificant trend in favor of prochlorperazine lowering the pain score to a greater degree.
Note that the 20 mg dose of metoclopramide is higher than what is traditionally used in most emergency departments, but escalating the dose of up to 20 mg over a few hours may be more efficacious (the slower the administration and the simultaneous use of diphenhydramine decreases risk of dystonic reactions).
References
Friedman, et al. "A Randomized Controlled Trial of Prochlorperazine Versus Metoclopramide for the Treatment of Acute Migraine." Annals of Emergency Medicine. 52:4, 399-406, October 2008.
