Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study).

Objective: We investigated whether metoclopramide administered with diphenhydramine (MAD) relieves headache in pregnant women when acetaminophen alone is ineffective, using codeine for comparison.

Study Design: Normotensive pregnant women in the second or third trimester were randomized to MAD intravenously (10 mg and 25 mg, respectively) or codeine orally (30 mg) for headache after 650 to 1,000 mg of acetaminophen failed to relieve their headaches. Headache severity (pain score 0-10) was noted at intervals over 24 hours.