100 Migraine Drugs, A to Z: metoclopramide

Metoclopramide (Reglan) is an anti-nausea drug that has been in use since 1979. Controlled studies have shown that metoclopramide stops not only nausea and vomiting that often accompany migraine attacks, but also relieves the pain.

The American Headache Society (AHS) and the European Federation of Neurological Societies (EFNS) guidelines on the management of adults with acute migraine recommend intravenous metoclopramide as an effective and recommended treatment in the management of acute migraine. While intravenous (IV) administration is preferred, intramuscular (IM), subcutaneous (SC) and oral routes are also effective.

These guidelines were based on many high-quality blinded studies such as one comparing 10 mg of IV metoclopramide with 600 mg of ibuprofen in which metoclopramide was clearly superior. A meta-analysis of 13 studies of intravenous metoclopramide involving 655 patients showed that “Metoclopramide is an effective treatment for migraine headache..” and that “Given its non-narcotic and antiemetic properties, metoclopramide should be considered a primary agent in the treatment of acute migraines in emergency departments”. Another emergency room study that was done after this meta-analysis was published, compared IV metoclopramide with IV ketorolac (an NSAID pain drug) and IV valproate, (an epilepsy drug approved in a pill form for the prevention of migraines) in 330 patients. Metoclopramide was the most effective of the three.

We give IV metoclopramide in the office and prescribe it in a tablet form. However, this drug is not free of side effects. Drowsiness is one of the common side effects, but a much more unpleasant side effect is severe restlessness or akathisia. Some patients describe it as wanting to crawl out of their skin, being very restless and very uncomfortable. This side effect can be relieved by diphenhydramine (Benadryl) given IV or as a tablet. According to one study, the incidence of this side effect is 6% if the IV infusion is given over 15 minutes and 25% if given as a “push” in under a minute. We usually give it as a “push” and find that significantly fewer than 20% of patients develop this side effect.

A much more serious side effect of metoclopramide is tardive dyskinesia or involuntary movements of the mouth, face or another part of the body. The FDA warning states in part:
“The development of this condition is directly related to the length of time a patient is taking metoclopramide and the number of doses taken. Those at greatest risk include the elderly, especially older women, and people who have been on the drug for a long time. Tardive dyskinesia is rarely reversible and there is no known treatment. However, in some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped”. A recent review estimates that tardive dyskinesia happens in less than 1% of patients.

This very rare but devastating side effect is not likely to occur in our patients who receive this drug very infrequently, only for emergencies. However, the thought of tardive dyskinesia is always lurking in the back of our minds so we tend to use IV ondansetron (Zofran) to treat nausea. Ondansetron does not help with pain and we have to combine it with IV ketorolac (Toradol) or another drug, but it is safer.