Typical antipsychotic agents produce central nervous system effects, especially extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Nearly every patient who receives neuroleptic therapy has one or more identifiable risk factors for TD, among the most significant of which are older age, female gender, presence of EPS, diabetes mellitus, affective disorders, and certain parameters of neuroleptic exposure (i.e. dose and duration of therapy). The typical course of TD is a gradual onset after several years of drug therapy, followed by slow improvement or remission, but a large number of patients have persistent TD with irreversible symptoms. In the management of TD, the patient's mental status is of primary concern. Currently, no uniformly safe and effective therapies for TD exist, though a variety of therapeutic agents, including some of the atypical neuroleptics, have been reported to treat TD successfully in some patients. Because TD liability is so much lower with novel antipsychotic therapy, all patients who have TD or are at risk for TD, as well as EPS, should be considered candidates for switching to these new drugs.

BACKGROUND:Metoclopramide hydrochloride, a neuroleptic dopamine receptor antagonist used to treat gastric ailments, is reported to cause extrapyramidal movement disorders. The goals of this study were (1) to determine the prevalence and severity of tardive dyskinesia and acute extrapyramidal movement syndromes including akathisia, acute dystonia, and drug-induced parkinsonism in metoclopramide-treated patients and (2) to compare the prevalence and severity of tardive dyskinesia in metoclopramide-treated diabetics and nondiabetics.METHODS:From a list of metoclopramide-treated patients received from the Portland (Ore) Veterans Affairs Medical Center pharmacy, 53 patients met inclusion criteria and 51 (96%) agreed to participate. Controls consisted of a convenience sample drawn from the Portland Veterans Affairs Medical Center Outpatient Clinic who were matched to subjects on age (+/- 10 years), gender, and presence or absence of diabetes. Of 61 potential controls contacted, 51 (84%) agreed to participate. Metoclopramide-treated subjects and controls were seen by a rater who was "blind" to all diagnoses and treatments. The rater performed a standardized examination used to elicit signs and symptoms of tardive dyskinesia and acute extrapyramidal movement syndromes.RESULTS:The relative risk for tardive dyskinesia was 1.67 (95% confidence interval, 0.93 to 2.97), and the relative risk for drug-induced parkinsonism was 4.0 (95% confidence interval, 1.5 to 10.5). Metoclopramide-treated patients had significantly greater severity of tardive dyskinesia, drug-induced parkinsonism, and subjective akathisia than controls. Use of metoclopramide was associated with impairment in ambulation and increased use of benzodiazepines. Metoclopramide-treated diabetics had significantly greater severity of tardive dyskinesia than metoclopramide-treated nondiabetics.CONCLUSIONS:Metoclopramide use is associated with a significantly increased prevalence and severity of several extrapyramidal movement disorders.

Recognition of tardive dyskinesia (TD) and other neuroleptic, drug-induced, extrapyramidal side effects presents a major challenge in modern clinical psychopharmacology. Failure to recognize these disorders can lead to poor patient care and may contribute to societal pressure for external control of psychiatric practice. This study reports the occurrence of tardive dyskinesia and drug-induced parkinsonism (DIP) in 101 inpatients, and documents underrecognition of both disorders by resident physicians. Researchers noted TD in 28% of cases and residents only described TD (or symptoms of TD) in 12%. The researcher determined DIP prevalence rate of 26% contrasted with an 11% rate found by residents. Patients with psychotic disorders were more likely than other patients to have researcher-identified TD, whereas DIP (researcher cases) occurred more often in patients with affective diagnoses. Residents tended to miss milder cases of TD, and to miss DIP in younger patients and in patients with affective disorders. Improved teaching and clinical exams are recommended to improve recognition.

Longitudinal evaluation of psychiatric patients often yields information that cross-sectional study does not. We previously examined 31 older (age > 55) chronic schizophrenics for prevalence of extrapyramidal side effects, severity of psychiatric symptoms, and ventricular brain ratio (VBR). We reexamined 22 of these patients after 2–4 years. Tardive dyskinesia (TD) and drug-induced parkinsonism (DIP) were common (mean prevalences were 52% and 62%, respectively) and often occurred together (38%). The overall prevalences of the disorders did not change significantly with time, although there was some individual fluctuation in diagnosis. Severity of TD was constant, but severity of DIP decreased, probably because neuroleptic doses were significantly decreased. Magnitude of DIP was positively correlated with VBR and severity of negative symptoms of schizophrenia. The correlation of DIP and negative symptoms occurred primarily because of the similarity between masked facies and blunted affect. VBR did not change over the follow-up period. Negative symptoms of schizophrenia were prevalent, moderately severe, and quite stable over time in this cohort. Positive symptoms were less severe but highly variable between examinations.

In a controlled study, we compared the prevalence of tardive dyskinesia in 38 neuroleptic-treated diabetics with the prevalence of tardive dyskinesia in a group of 38 nondiabetic neuroleptic-treated controls, matched for age, sex, psychiatric diagnosis, and dose and duration of neuroleptic treatment. Members of each group were evaluated for movement disorders by a rater who used standard rating scales and was "blind" to all diagnoses and treatments. Neuroleptic-treated diabetics had a significantly higher prevalence and severity of tardive dyskinesia. There were no differences between groups on other possible risk factors for tardive dyskinesia, including parkinsonism, anticholinergic drug treatment, or cognitive function. These data suggest that diabetes mellitus should be examined further as a risk factor for tardive dyskinesia.

Using multivariate statistical analyses, the authors identified risk factors for development of drug-induced parkinsonism (DIP) in 66 tardive dyskinesia (TD) patients. Older age, recent use of neuroleptics, shorter duration of past neuroleptic exposure, and severity of TD were associated with increased risk of DIP. The clinician should devise treatment strategies in anticipation of the occurrence of DIP regardless of the presence or absence of TD, especially in older patients. New models for the pathophysiology of the two disorders are needed.

Letters and Corrections1 May 1983Metoclopramide Side EffectsDANIEL E. CASEY, M.D.DANIEL E. CASEY, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-5-673_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Additional information on the neurologic side effects of metoclopramide should be added to the review of Albibi and McCallum (1). Because metoclopramide blocks dopamine receptors and produces behavioral and biochemical signs of receptor hypersensitivity (2), it probably is similar to other neuroleptics in causing drug-induced dyskinesias.Of primary concern is the capacity of prolonged metoclopramide use to produce tardive dyskinesia, a potentially irreversible syndrome of abnormal involuntary movements that occurs more frequently with increasing age and may not be evident until the drug is discontinued. Although the first case of metoclopramide-associated tardive dyskinesia occurred in a patient...References1. ALBIBI R and MCCALLUM R. Metoclopramide: pharmacology and clinical application. Ann Intern Med. 1983;98:86-95. LinkGoogle Scholar2. STANLEY M, ROTROSEN J, LAUTIN A, WAZER D, and GERSHON S. Tardive dyskinesia and metoclopramide [Letter]. Lancet. 1979;2:1190. CrossrefMedlineGoogle Scholar3. LAVY S, MELAMED E, and PENCHAS S. Tardive dyskinesia associated with metoclopramide. Br Med J. 1978;1:77-8. CrossrefMedlineGoogle Scholar4. GRIMES J, HASSAN M, and PRESTON D. Adverse neurological effects of metoclopramide. Can Med Assoc J. 1982;126:23-5. MedlineGoogle Scholar5. GRIMES J, HASSAN M, and KRELINA M. Long-term follow-up of tardive dyskinesia due to metoclopramide [Letter]. Lancet. 1982;2:563. CrossrefMedlineGoogle Scholar6. JUNGMANN E and SCHÖFFLING K. Akathisia and metoclopramide [Letter]. Lancet. 1982;2:221. CrossrefMedlineGoogle Scholar1. ALBIBI R and MCCALLUM R. Metoclopramide: pharmacology and clinical application. Ann Intern Med. 1983;98:86-95. LinkGoogle Scholar2. SCHULTZ-DELRIEU K. Metoclopramide. N Engl J Med. 1981;305:28-33. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DANIEL E. CASEY, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe effects of pyridoxine (vitamin B6) supplementation in nausea and vomiting during pregnancy: a systematic review and meta-analysisThe tardive syndromesMidazolam vs. Diphenhydramine for the Treatment of Metoclopramide-induced Akathisia: A Randomized Controlled TrialThe Tardive SyndromesA randomized, double-blind, placebo controlled comparison of droperidol, ondansetron, and metoclopramide for the prevention of vomiting following outpatient strabismus surgery in childrenClozapine treatment of persistent paroxysmal dyskinesia associated with concomitant paroxetine and sumatriptan useACUTE DYSKINESIAS AFTER METOCLOPRAMIDE WITHDRAWALAmisulpride poisoning: a report on two casesNeuroleptic malignant-like syndrome induced by metoclopramideLife-threatening tardive dyskinesia caused by metoclopramideTreatment of Severe Reflux Esophagitis with Cimetidine and MetoclopramideDAVID A. LIEBERMAN, M.D., EMMET B. KEEFFE, M.D. 1 May 1983Volume 98, Issue 5_Part_1Page: 673-674KeywordsAntipsychoticsDopamineDrugsHypersensitivity ePublished: 1 December 2008 Issue Published: 1 May 1983 PDF downloadLoading ...