Review article: metoclopramide and tardive dyskinesia
Article first published online: 3 NOV 2009
© 2010 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 31, Issue 1, pages 11–19, January 2010
How to Cite
RAO, A. S. and CAMILLERI, M. (2010), Review article: metoclopramide and tardive dyskinesia. Alimentary Pharmacology & Therapeutics, 31: 11–19. doi: 10.1111/j.1365-2036.2009.04189.x
- Issue published online: 2 DEC 2009
- Article first published online: 3 NOV 2009
- Publication data Submitted 14 August 2009 First decision 14 September 2009 Resubmitted 15 September 2009 Accepted 31 October 2009 Epub Accepted Article 3 November 2009
Background Metoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In 2009, the FDA issued a black box warning regarding long-term or high-dose use of this medication because of the risk of developing tardive dyskinesia.
Aims To review the mechanism of action and pharmacokinetic properties of metoclopramide, the risk of metoclopramide-induced tardive dyskinesia, potential mechanisms that may alter and to summarize the clinical context for appropriate use of the drug.
Methods We conducted a PubMed search using the following key words and combined searches: metoclopramide, neuroleptics, tardive dyskinesia, incidence, prevalence, dopamine, receptors, pharmacokinetic, pharmacology, pharmacogenetics, DRD3 Ser9Gly polymorphism, cytochrome P450, p-glycoprotein, risk factors, gastroparesis, outcome, natural history.
Results Available data show that risk of tardive dyskinesia from metoclopramide use is likely to be <1%, much less than the estimated 1–10% risk previously suggested in national guidelines. Tardive dyskinesia may represent an idiosyncratic response to metoclopramide; pharmacogenetics affect pharmacokinetic and dopamine receptor pharmacodynamics in response to neuroleptic agents that cause similar neurological complications.
Conclusion Community prevalence and pharmacogenetic mechanisms involved in metoclopramide-induced tardive dyskinesia require further study to define the benefit-risk ratio more clearly.