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Review article: metoclopramide and tardive dyskinesia
Open accessAbstract
Summary: 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.
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“Its most serious side effect is the occurrence of extrapyramidal movement disorders, tardive dyskinesia, and akathisia in a significant number of patients (30-40%). Drowsiness, fatigue, and depression also occur frequently.”
From Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review (2018) · cites this paper as [56]
Experimental — accuracy not yet measuredIn the citing paper
“The Food and Drug Administration has a black box warning against the chronic use of metoclopramide [56].”
From Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review (2018) · cites this paper as [56]
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Rapid Determination of Metoclopramide Level in Human Plasma by LC-MS/MS Assay
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Treatment of Clozapine-Associated Sialorrhea
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“Regarding metoclopramide toxicity, Rao and Camilleri [20] conducted a review of the evidence on the frequency of late dyskinesia, the most feared side effect, leading to the FDA warning.”
BackgroundGastric motility disorders and their endoscopic and surgical treatments other than bariatric surgery
Soliman, H., Mariano, G., Duboc, H., Giovinazzo, D., Coffin, B., Gourcerol, G., & Moszkowicz, D. (2022) · Journal of Visceral Surgery · doi:10.1016/j.jviscsurg.2022.01.003 · Cited by 7
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“Metoclopramide is a substituted benzamide derivative used widely for relief of multiple gastrointestinal symptoms, facilitating gut motility via antagonism of enteric neuronal and muscular inhibitory D2 receptors.(71,72) Antiemetic effects derive from central inhibition of D2 and 5-HT3 receptors within the chemorecept…”
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Metadata
- Authors
- RAO, A. S., & CAMILLERI, M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- CAMILLERI, M.
- ORCID
- CAMILLERI, M.
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2009-12-02
- Volume
- 31
- Issue
- 1
- Pages
- 11-19
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- OpenAlex
- W2049233278
- Cited by
- 316
- References
- 38
- Citations by year
- 2026: 15 · 2025: 8 · 2024: 11 · 2023: 16 · 2022: 33 · 2021: 21 · 2020: 24 · 2019: 28 · 2018: 24 · 2017: 21 · 2016: 22 · 2015: 25 · 2014: 18 · 2013: 21 · 2012: 12
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Surgery › Nausea and vomiting management
- Keywords
- metoclopramide, tardive dyskinesia, dopamine antagonists, pharmacokinetics, pharmacogenetics, cytochrome P450, P-glycoprotein, gastroparesis, black box warning, risk factors, risk-benefit assessment
- MeSH terms
- Dyskinesia, Drug-Induced, Humans, Metoclopramide, Risk Factors, Prevalence, Odds Ratio, Dopamine Antagonists
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