100 Migraine Drugs, A to Z: prochlorperazine

Prochlorperazine (Compazine) belongs to the category of phenothiazine drugs. Chlorpromazine (Thorazine) was the first drug in this family and it was approved for the treatment of schizophrenia in 1950. Phenothiazine drugs have also been found to be effective for the treatment of nausea and vomiting, severe anxiety, and persistent hiccups.

Prochlorperazine is mostly used for the treatment of nausea and vomiting and it is available in tablets, rectal suppositories, and injections. Prochlorperazine appears to be an effective drug not only for the treatment of nausea and vomiting of migraine, but also for head pain and other symptoms.

Prochlorperazine was found to be more effective in treating all migraine symptoms than another antiemetic (nausea drug), metoclopramide (Reglan). In a study of children with migraine seen in an emergency department, intravenous prochlorperazine was more effective than an intravenous pain medication ketorolac (Toradol).

The main side effect of prochlorperazine is restlessness or akathisia, which occurs in a large minority of patients who receive it intravenously. In many patients this symptom is mild but in some, it is severe and extremely unpleasant. Many describe the sensation as if wanting to crawl out of their skin. With regular long-term intake of phenothiazine medications, involuntary movements can be a very serious side effect.

I do have patients for whom chlorpromazine works exceptionally well and with no side effects. Most of them need it not more than a few times a month and most use tablets and less often, suppositories. Suppositories work faster than tablets and are preferred by patients who experience vomiting with their migraines. I also use it occasionally as an intravenous injection in the office when a patient is known to respond to it well or when ondansetron (Zofran), a safer antiemetic, is ineffective.