Promethazine (Phenergan) is a phenothiazine drug that can be very effective for the treatment of migraine-induced nausea and vomiting. Like other phenothiazine drugs, it can have some direct effect on pain of migraine although it has not been studied as extensively as prochlorperazine or metoclopramide.
A double-blind study in 216 patients comparing sumatriptan with promethazine with sumatriptan alone, showed that the combination was more effective in relieving pain, achieving pain-free state, and preventing recurrence of migraine.
Promethazine is available as a tablet and injection as well as a rectal suppository which is very useful for patients with severe nausea and vomiting.
Side effects of promethazine are similar to other phenothiazine drugs and include drowsiness, dizziness, and akathisia or restlessness. This restlessness can be very unpleasant but can be treated with oral or injected diphenhydramine (Benadryl).
