Ondansetron (Zofran) is not a migraine drug per se, but it is used for the treatment of nausea that often accompanies a migraine attack. It belongs to a different class of nausea drugs than the older drugs such as prochlorperazine (Compazine), promethazine (Phenergan) or metoclopramide (Reglan). which are effective for both nausea and pain of migraine.
There are no good studies of ondansetron for the treatment of migraines, but the impression of most headache specialists is that it is helpful only for the treatment of nausea of migraine and not the pain. However, one large observational study does suggest that it may help more than just nausea, at least in children. Observational studies are much less reliable than double-blind placebo-controlled ones, however, the large size of this study provides some compensation for this deficiency. The researchers looked at the records of 32,124 children with migraine who presented to the emergency room. One fifth received ondansetron and it was as effective in preventing a return visit to the ER as metoclopramide, while prochlorperazine was a bit more effective.
The advantage of ondansetron is that it does not cause neurological symptoms of restlessness (akathisia) and drowsiness, which can occur with metoclopramide and prochlorperazine.
Ondansetron is available in a tablet, an orally disintegrating tablet, and as an injection, but not as a suppository. Rectal suppositories of prochlorperazine and promethazine work fast and are very useful for patients who are vomiting and cannot hold down a tablet.
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