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      Trimetazidine-Induced Parkinsonism: A Systematic Review

      systematic-review

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          Abstract

          Importance: Trimetazidine (TMZ) is a medication given to patients with stable coronary artery disease. While it is reportedly well-tolerated, there are increasing numbers of reports of adverse events such as parkinsonism.

          Objectives: The purpose of this study was to systematically review the currently available literature on TMZ-induced parkinsonism.

          Evidence Review: A search of Scopus, MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, PubMed, Science Direct, and Google Scholar was conducted on or before November 7, 2019. The literature search included cohort studies, prospective and/or retrospective studies, meta-analysis, and other systematic reviews published as an original article, including abstracts and full texts. We included patients taking TMZ who developed one or more of the parkinsonian symptoms of bradykinesia, tremors, rigidity, and postural instability, where these symptoms improved after withdrawal of the said medication.

          Findings: There are currently five studies on TMZ use and associated parkinsonism. The literature included two case reports, one case series, and one retrospective and one prospective study. We found no results from randomized clinical trials. Overall, 88 patients developed TMZ-induced parkinsonism. Regression of parkinsonism was reported in all of the participants after withdrawal of TMZ. A total of 49 patients (55.7%) had complete regression of symptoms, while 39 patients (44.3%) had significant reduction of symptoms. The duration between TMZ (dose, 60–80 mg/day) intake and onset of symptoms ranged from 4 months to 20 years. The most commonly reported extrapyramidal symptoms were akinesia, rigidity, postural disturbances, and gait disorders, which were usually mild and symmetric.

          Conclusions and Relevance: The current literature suggests that TMZ can induce parkinsonism that is reversible with drug withdrawal. It is warranted to examine patients, especially the elderly, on TMZ for parkinsonian symptoms and those with pre-existing neurodegenerative diseases. Further studies are needed to assess the risk-benefit ratio of this drug, especially in the elderly age group.

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          Parkinsonism and Parkinson's disease in the elderly: a community-based survey in Brazil (the Bambuí study).

          Débora Palma Maia, Giselle Lima, Tiago Barbosa … (2006)
          Several community-based surveys on the prevalence of Parkinsonism and Parkinson's disease have been conducted worldwide, with variations on their methodology and results. The objective of this study is to assess the prevalence of Parkinsonism and its causes in a cohort of individuals age 64 years or older in Bambuí, a Brazilian town. In phase I, 1,186 people older than 64 years responded to a 9-question screening questionnaire for Parkinsonism. In phase II, all subjects who scored > or = 2 points on the test were examined independently by at least 2 movement disorder-trained physicians. A movement disorder senior specialist excluded or confirmed the diagnosis in all suspected cases. The response rate was high for both phases (96% for phase I and 94% for phase II). The prevalence rate per 100 population over 64 years of age in this group was 7.2% for Parkinsonism of all types (n = 86). The most frequent causes were idiopathic Parkinson's disease and drug-induced Parkinsonism, with prevalence rates of 3.3% (n = 39) and 2.7% (n = 32), respectively. The prevalence of vascular Parkinsonism was 1.1% (n = 13). We found 1 case of posttraumatic Parkinsonism and another with multiple system atrophy. In this first population-based study of Parkinsonism conducted in Brazil, the prevalence in a cohort of elderly subjects was higher than the observed in other populations worldwide, especially because of the high rates of drug-induced and vascular Parkinsonism. The prevalence of Parkinson's disease was similar to that observed in elderly people in door-to-door surveys in other American, European, and Eastern countries.
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            Drug-induced parkinsonism: a review of 17 years' experience in a regional pharmacovigilance center in France.

            Jean-Louis Montastruc, Santiago Lloret, Emmanuelle Bondon-Guitton … (2011)
            Besides antipsychotics, several drugs can induce parkinsonism. We review spontaneous notifications of drug-induced or -worsened parkinsonism to a French regional pharmacovigilance center between 1993 and 2009. During these 17 years, 20,855 adverse drug reactions have been reported, including 155 (0.7%) cases of drug-induced or -worsened parkinsonism. Most of the notifications have involved aged patients (48% between 60 and 79 years) and females (60%). "Seriousness" was found in 43.9% of cases. Worsening of parkinsonism occurred in 28 patients suffering from idiopathic Parkinson's disease. Sixty-nine percent of drug-induced or -worsened parkinsonism cases were observed during the first 3 months after introduction of the "suspect" drug (involving mainly central dopaminergic antagonists). A second peak (20%) was found 12 months after drug introduction (mainly caused by calcium channel blockers). The most frequently reported parkinsonian symptom was rigidity (78.7%). The three cardinal symptoms were found in 37.4% of notifications. Evolution was favorable (after partial or complete withdrawal of suspect drug[s]) in 88.7% of cases. Among the 261 suspect drugs, most involved central dopaminergic antagonists (49%), followed by antidepressants (8%), calcium channel blockers (5%), peripheral dopaminergic antagonists (5%), and H1 antihistamines (5%). Cases with lithium, valproic acid, amiodarone, anticholinesterases, or trimetazidine were also found. Three notifications were the result of pharmacokinetic interactions. We found that drug-induced or -worsened parkinsonism is an often "serious," but reversible, adverse drug reaction. It occurred more frequently between 60 and 79 years. Rigidity was the most frequently reported symptom. Approximately 50% of drug-induced or -worsened parkinsonism cases spontaneously reported were related to drugs other than antipsychotics. Drug-induced or -worsened parkinsonism can also be explained by pharmacokinetic drug interactions. Copyright © 2011 Movement Disorder Society.
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              Defining the Role of Trimetazidine in the Treatment of Cardiovascular Disorders: Some Insights on Its Role in Heart Failure and Peripheral Artery Disease

              Piotr Chrusciel, Jacek Rysz, Maciej Banach (2014)
              Trimetazidine is a cytoprotective drug whose cardiovascular effectiveness, especially in patients with stable ischemic heart disease, has been the source of much controversy in recent years; some have gone so far as to treat the medication as a ‘placebo drug’ whose new side effects, such as Parkinsonian symptoms, outweigh its benefits. This article is an attempt to present the recent key studies, including meta-analyses, on the use of trimetazidine in chronic heart failure, also in patients with diabetes mellitus and arrhythmia, as well as in peripheral artery disease. This paper also includes the most recent European Society of Cardiology guidelines, including those of 2013, on the use of trimetazidine in cardiovascular disease.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Neurol
                Journal ID (iso-abbrev): Front Neurol
                Journal ID (publisher-id): Front. Neurol.
                Title: Frontiers in Neurology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-2295
                Publication date (Electronic): 25 February 2020
                Publication date Collection: 2020
                Volume: 11
                Electronic Location Identifier: 44
                Affiliations
                [1] 1Department of Clinical Neurosciences, University of the East Ramon Magsaysay Memorial Medical Center, Inc. , Quezon City, Philippines
                [2] 2Section of Neurology, Department of Internal Medicine, Cardinal Santos Medical Center , San Juan, Philippines
                [3] 3Department of Surgery, Rizal Medical Center , Pasig, Philippines
                [4] 4Movement Disorder Service and Section of Neurology, Institute for Neurosciences, St. Luke's Medical Center , Quezon, Philippines
                [5] 5Department of Neurosciences, College of Medicine – Philippine General Hospital, University of the Philippines Manila , Manila, Philippines
                Author notes

                Edited by: Steven Frucht, Mount Sinai Hospital, United States

                Reviewed by: Joshua M. Shulman, Harvard University, United States; Silmar Teixeira, Federal University of Piauí, Brazil

                *Correspondence: Roland Dominic G. Jamora rgjamora@ 123456up.edu.ph

                This article was submitted to Movement Disorders, a section of the journal Frontiers in Neurology

                Article
                DOI: 10.3389/fneur.2020.00044
                PMC ID: 7052178
                PubMed ID: 32158422
                SO-VID: ce199954-fac9-4b2d-8986-78d0da700d57
                Copyright © Copyright © 2020 Dy, Limjoco and Jamora.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 04 August 2019
                Date accepted : 13 January 2020
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 20, Pages: 6, Words: 4051
                Categories
                Subject: Neurology
                Subject: Systematic Review

                ScienceOpen disciplines: Neurology
                Keywords: parkinsonism,trimetazidine,drug-induced,trimetazidine-induced parkinsonism,reversible parkinsonism
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: parkinsonism, trimetazidine, drug-induced, trimetazidine-induced parkinsonism, reversible parkinsonism

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