Review article: metoclopramide and tardive dyskinesia

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.