Metoclopramide Related Tardive Dyskinesia & Dystonia
Metoclopramide is widely used for relief of upper gastrointestinal
symptoms such as heartburn, nausea, and vomiting. Adverse reactions
are relatively rare,' but may include disturbances of the central
nervous system such as drowsiness, restlessness, and dizziness.'
Recently acute facial dyskinesias and dystonia' have been reported in
several children and young adults shortly after administration of low
doses of metoclopramide. These extrapyramidal effects were attributed
to idiosyncrasy, and completely subsided in all cases after withdrawal
of the drug. We report on a patient who developed tardive dyskinesia
after long-term treatment with high doses of metoclopramide. We
know of no other report of such an association.
Case report
A 48-year-old Jewish man began to complain of persistent nausea without
vomiting or other gastrointestinal symptoms. No organic basis was found for
his complaint, and results of physical and neurological examinations as well
as various laboratory tests were normal. There was no evidence of other
disease or metabolic abnormalities. There was no history of food or drug
allergies in the patient or in his family. Metoclopramide (Pramin, Rafa
Laboratories, Israel) was prescribed for the nausea. He took the drug by
mouth at a daily dose of 20-40 mg for about six years. He asked for the
dosage to be gradually increased, and during the last four years he
consistently ingested eight tablets (80 mg) daily without any side effects.
Because he could not get metoclopramide without prescription while his
regular doctor was away, he abruptly stopped taking the drug.
Ten days later he progressively developed severe persistent facial dyskinesia
consisting of repetitive involuntary movements of the lips, jaws, cheeks, and
tongue. The latter were mainly constant, forceful sucking, chewing,
grimacing, and rapid protrusions of the tongue. Results of general physical
and neurological examinations were otherwise normal. Blood count, sedimentation
rate, and biochemical and serological examinations showed nothing
abnormal. The patient had never received other drugs known-to be associated
with involuntary movements, such as phenothiazines or butyrophenones.
Readministration of metoclopramide at a daily dose of 30 mg resulted in
almost complete disappearance of the involuntary movements. Another
attempt to withdraw the drug was associated with- recurrence of the
dyskinesia, which subsided when metoclopramide was given again.
Comment
The severe involuntary movements developed by this patient after
chronic use of high doses of metoclopramide are identical to the
syndrome of tardive dyskinesia. The latter is commonly reported in
psychiatric patients after long-term administration of phenothiazines
or butyrophenones, particularly when these agents are abruptly
withdrawn or their dosage reduced.5 Similarly, our patient developed
this extrapyramidal syndrome after long-term ingestion of metoclopramide and sudden discontinuation. Phenothiazines and butyrophenones are potent dopamine-receptor antagonists, and tardive
dyskinesia may be caused by a hypersensitivity of central dopamine
receptors induced by neuroleptics.6 Metoclopramide may block cerebral
dopamine receptors,7 and a similar mechanism may have operated in
our patient. Paradoxically, tardive dyskinesia sometimes improves
after readministration of neuroleptics.5 6 Similarly, the involuntary
movements in our patient also subsided after reinstitution of metoclopramide.
This report should alert doctors to the risk that patients may
develop serious and potentially irreversible extrapyramidal side effects after long-term use of metoclopramide.
1. Pinder, R M, et al, Drugs, 1976, 12, 81.
2 Melmed, S, and Bank, H, British Medical Journal, 1975, 1, 331.
3 Van Daele, M C, Archives of Disease in Childhood, 1970, 45, 130.
4 Cochlin, D L, British Journal of Clinical Practice, 1974, 28, 201.
5 Crane, G E, American Journal of Psychiatry, 1972, 129, 446.
6 Klawans, H L, American Journal of Psychiatry, 1973, 130, 82.
7 Dolphin, A, Psychopharmacology, 1975, 41, 133.
(Accepted 18 October 1977)
* Please Note: This article is old. It is being provided here to show the long length of time that Metoclopramide has been associated with increased risks and complications of tardive dyskinesia. Do not rely on this article in the diagnosis, treatment of tardive dyskinesia or any other illness or medical issue. Talk to you doctor about any medical problem or questions about your health.
