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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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“Use of metoclopramide should, therefore, be restricted to a maximum of 3 months, at the lowest possible dose [75].”
BackgroundMedication overuse and chronic migraine: a critical review according to clinical pharmacology
Ferrari, A., Baraldi, C., & Sternieri, E. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2015.1043265 · Cited by 38
Movement Disorders From the Use of Metoclopramide and Other Antiemetics in the Treatment of Migraine
Wijemanne, S., Jankovic, J. J., & Evans, R. W. (2015) · Headache The Journal of Head and Face Pain · doi:10.1111/head.12712 · Cited by 36
“Recent data show that the risk of tardive syndrome due to metoclopramide is likely to be <1%, much less than the estimated 1–10% risk previously suggested in national guidelines.(43) The risk of DIMD is related to the duration of treatment and the total cumulative dose.”
BackgroundTherapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis
Shin, A., & Wo, J. M. (2015) · Current Gastroenterology Reports · doi:10.1007/s11894-015-0430-8 · Cited by 36
Management of gastroparesis‐associated malnutrition
Bharadwaj, S., Meka, K. C., Tandon, P., Rathur, A., Rivas, J. M., Vallabh, H., Jevenn, A., Guirguis, J. K., Sunesara, I., Nishnick, A., et al. (2016) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12344 · Cited by 37
Sienaert, P. A., van Harten, P. N., & Rhebergen, D. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64012-3.00025-3 · Cited by 38
Khoury, T., Mizrahi, M., Mahamid, M., Daher, S., Nadella, D., Hazou, W., Benson, A., Massarwa, M., & Sbeit, W. (2018) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.14293 · Cited by 34
Advancement in the clinical management of intestinal pseudo-obstruction
Lauro, A., GIORGIO, R. D., & Pinna, A. D. (2014) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2014.940317 · Cited by 31
A Guide to the Extrapyramidal Side-Effects of Antipsychotic Drugs
Owens, D. G. C. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781139149112 · Cited by 32
Gastric Emptying Scans: Poor Adherence to National Guidelines
Wise, J. L., Vázquez‐Roque, M. I., McKinney, C. J., Zickella, M., Crowell, M. D., & Lacy, B. E. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06314-2 · Cited by 31
Tangible pathologies in functional dyspepsia
Walker, M. M., Potter, M. D. E., & Talley, N. J. (2019) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2019.101650 · Cited by 30
Advances in the Pharmacogenomics of Adverse Drug Reactions
Collins, S. L., Carr, D. F., & Pirmohamed, M. (2015) · Drug Safety · doi:10.1007/s40264-015-0367-8 · Cited by 31
“Metoclopramide [113]”
Drug‐drug interactions in pharmacologic management of gastroparesis
Youssef, A. S., Parkman, H. P., & Nagar, S. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12614 · Cited by 29
Hale, T. W., Kendall-Tackett, K. A., & Cong, Z. (2018) · Clinical Lactation · doi:10.1891/2158-0782.9.1.10 · Cited by 29
“Thus, the available data suggested that the risk of TD is probably less than 1% with the consumption of metoclopramide (Rao & Camilleri, 2010).”
BackgroundAn examination of three prescribing cascades in a cohort of older adults with dementia
Trenaman, S., Bowles, S., Kirkland, S., & Andrew, M. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02246-2 · Cited by 26
“The 180 day timeframe chosen was consistent with the amount of time required for any of the three inciting medications to cause their associated adverse event; urinary incontinence due to cholinesterase inhibitors typically presents within 26 weeks (182 days) of medication initiation [45, 46], metoclopramide carries a…”
Lin, S. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.10.001 · Cited by 29
Tardive Dyskinesia: Treatment Update
Arya, D., Khan, T., Margolius, A. J., & Fernandez, H. H. (2019) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-019-0976-1 · Cited by 28
Cavero‐Redondo, I., Álvarez‐Bueno, C., Pozuelo‐Carrascosa, D. P., Díez‐Fernández, A., & Notario‐Pacheco, B. (2015) · Journal of Clinical Nursing · doi:10.1111/jocn.12984 · Cited by 27
Movement Disorders and Psychosis, a Complex Marriage
van Harten, P. N., Bakker, P. R., Mentzel, C. L., Tijssen, M. A. J., & Tenback, D. E. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00190 · Cited by 26
“, long-term use of metoclopramide to treat nausea, or antipsychotics for insomnia (18, 19).”
BackgroundRelamorelin for the treatment of gastrointestinal motility disorders
Chedid, V. G., & Camilleri, M. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1373088 · Cited by 26
Self-citationGastric per-oral endoscopic myotomy: Current status and future directions
Podboy, A. J., Hwang, J. H., Nguyen, L. A. B., García, P., Zikos, T. A., Kamal, A., Triadafilopoulos, G., & Clarke, J. O. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i21.2581 · Cited by 26
Medical Treatment of Gastroesophageal Reflux Disease
Kroch, D. A., & Madanick, R. D. (2017) · World Journal of Surgery · doi:10.1007/s00268-017-3954-2 · Cited by 25
“Metoclopramide may cause CNS side effects including drowsiness, agitation, irritability, depression, dystonic reaction, and rarely (\1% of patients) tardive dyskinesia [52].”
BackgroundVela, M. F. (2014) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2013.12.001 · Cited by 25
Zikos, T. A., Nguyen, L. A. B., Kamal, A., Fernandez‐Becker, N., Regalia, K. A., Nandwani, M. C. R., Sonu, I. S., Garcia, M., Okafor, P. N., Neshatian, L., et al. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06195-5 · Cited by 23
Gastric per-Oral Endoscopic Myotomy for Refractory Gastroparesis: A Meta-Analysis
Li, P., Ma, B., Gong, S., Zhang, X., & Li, W. (2020) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-020-04520-x · Cited by 24
“Currently, the first-line therapies for treating gastroparesis are lifestyle modification, diet modification, and antiemetic and/or pro-kinetic medications; however, only metoclopramide is approved by the US Food and Drug Administration, and its long-term efficacy was limited with a black-box warning for tardive dyski…”
BackgroundLebares, C. C., & Swanström, L. L. (2016) · Gastrointestinal Endoscopy Clinics of North America · doi:10.1016/j.giec.2015.12.012 · Cited by 24
“Metoclopramide, the only US Food and Drug Administration (FDA)-approved medication for gastroparesis treatment in the United States, currently carries a black-box warning of tardive dyskinesia, and prolonged use is associated with tachyphylaxis.(22) Gastric electrical stimulation is currently FDA-approved on protocol…”
BackgroundIdentification and management of tardive dyskinesia: A case series and literature review
Khouzam, H. R. (2015) · Postgraduate Medicine · doi:10.1080/00325481.2015.1074031 · Cited by 23
“The various TD risk factors are summarized in Table 2 [18-23].”
BackgroundBapaye, A., Korrapati, S. K., Dharamsi, S., & Dubale, N. A. (2019) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001296 · Cited by 23
Latest developments in chronic intestinal pseudo-obstruction
Zhu, C., Zhao, H.-W., Lin, H., Feng, W., & Li, Y. (2020) · World Journal of Clinical Cases · doi:10.12998/wjcc.v8.i23.5852 · Cited by 23
van der Vorst, M. J. D. L., Toffoli, E. C., Beusink, M., Linde, M. E. V., van Voorthuizen, T., Brouwer, S., van Zweeden, A. A., Vrijaldenhoven, S., Berends, J. C., Berkhof, J. H., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2020-0305 · Cited by 23
“Lower doses (25–50 mg) are associated with a very low incidence (<1%) of dyskinetic or extrapyramidal symptoms [31].”
BackgroundThe investigational drug camicinal for the treatment of gastroparesis
Barshop, K., & Kuo, B. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.975792 · Cited by 22
“It is not indicated for longer than a 12-week period [9], as it may have extrapyramidal side effects such as akathisia through its central D2 antagonism [10].”
Background
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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