{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:27:04Z","timestamp":1793503624347,"version":"4.5.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antipsychotic agents are the basis for the pharmacological management of acute and chronic schizophrenia, bipolar disorders, mood disorders with psychotic feature, and other psychotic disorders. Antipsychotic medication use is frequently associated with unfavorable adverse effects such as extrapyramidal side effects (EPSEs). Hence, this systematic review and meta-analysis was aimed to determine the magnitude of antipsychotic-induced EPSEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      A literature search was conducted using legitimate databases, indexing services, and directories including PubMed\/MEDLINE (Ovid\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ), EMBASE (Ovid\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ), google scholar and WorldCat to retrieve studies. Following screening and eligibility, the relevant data were extracted from the included studies using an Excel sheet and exported to STATA 15.0 software for analyses. The Random effects pooling model was used to analyze outcome measures at a 95% confidence interval. Besides, publication bias analysis was conducted. The protocol has been registered on PROSPERO with ID: CRD42020175168.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>In total, 15 original articles were included for the systematic review and meta-analysis. The pooled prevalence of antipsychotic-induced EPSEs among patient taking antipsychotic medications was 37% (95% CI: 18\u201355%, before sensitivity) and 31% (95% CI: 19\u201344%, after sensitivity). The prevalence of antipsychotic-induced parkinsonism, akathisia, and tardive dyskinesia was 20% (95% CI: 11\u201328%), 11% (95% CI: 6\u201317%), and 7% (95% CI: 4\u20139%), respectively. To confirm a small-study effect, Egger\u2019s regression test accompanied by funnel plot asymmetry demonstrated that there was a sort of publication bias in studies reporting akathisia and tardive dyskinesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The prevalence of antipsychotic-induced EPSEs was considerably high. One in five and more than one in ten patients experienced parkinsonism and akathisia, respectively. Appropriate prevention and early management of these effects can enhance the net benefits of antipsychotics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0257129","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T13:27:52Z","timestamp":1631280472000},"page":"e0257129","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":82,"title":["Antipsychotic-induced extrapyramidal side effects: A systematic review and meta-analysis of observational studies"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0523-8336","authenticated-orcid":true,"given":"Tilahun","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mekonnen","family":"Sisay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandaras","family":"Tariku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham Nigussie","family":"Mekuria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6065-0708","authenticated-orcid":true,"given":"Assefa","family":"Desalew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"issue":"2","key":"pone.0257129.ref001","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/JCP.0b013e318036bfbb","article-title":"Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis","volume":"27","author":"C Paton","year":"2007","journal-title":"Journal of clinical psychopharmacology"},{"issue":"4","key":"pone.0257129.ref002","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2165\/00023210-200418040-00005","article-title":"Dopamine partial agonists","volume":"18","author":"JA Lieberman","year":"2004","journal-title":"CNS drugs"},{"issue":"3","key":"pone.0257129.ref003","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/wps.20567","article-title":"Management of common adverse effects of antipsychotic medications","volume":"17","author":"TS Stroup","year":"2018","journal-title":"World Psychiatry"},{"issue":"2","key":"pone.0257129.ref004","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/(SICI)1099-1077(200003)15:2<79::AID-HUP146>3.0.CO;2-6","article-title":"Extrapyramidal symptoms and residual psychopathology with low-dose neuroleptics","volume":"15","author":"D Berardi","year":"2000","journal-title":"Human Psychopharmacology: Clinical and Experimental"},{"issue":"2","key":"pone.0257129.ref005","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/YIC.0b013e328334e5a8","article-title":"The effects of psychopathology on subjective experience of side effects of antipsychotics in patients with schizophrenia","volume":"25","author":"SS-H Hwang","year":"2010","journal-title":"International clinical psychopharmacology"},{"issue":"3","key":"pone.0257129.ref006","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1080\/10673220600748486","article-title":"Side effects of atypical antipsychotics: extrapyramidal symptoms and the metabolic syndrome","volume":"14","author":"AA Shirzadi","year":"2006","journal-title":"Harvard review of psychiatry"},{"key":"pone.0257129.ref007","article-title":"Novel antipsychotics, extrapyramidal side effects and tardive dyskinesia","author":"TR Barnes","year":"1998","journal-title":"International clinical psychopharmacology"},{"issue":"11","key":"pone.0257129.ref008","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1177\/0706743718786702","article-title":"Antipsychotic drug-induced movement disorders: a forgotten problem?","volume":"63","author":"T Pringsheim","year":"2018","journal-title":"The Canadian Journal of Psychiatry"},{"issue":"9","key":"pone.0257129.ref009","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1212\/01.wnl.0000227186.29062.8a","article-title":"Drug Induced Movement Disorders","volume":"67","author":"MW Halterman","year":"2006","journal-title":"Neurology"},{"issue":"5","key":"pone.0257129.ref010","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/sj.mp.4002142","article-title":"Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions","volume":"13","author":"P Bakker","year":"2008","journal-title":"Molecular psychiatry"},{"issue":"2","key":"pone.0257129.ref011","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s40120-018-0105-0","article-title":"Antipsychotic-Related Movement Disorders: Drug-Induced Parkinsonism vs. Tardive Dyskinesia-Key Differences in Pathophysiology and Clinical Management","volume":"7","author":"KM Ward","year":"2018","journal-title":"Neurol Ther"},{"issue":"1","key":"pone.0257129.ref012","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1176\/appi.ajp.161.1.160","article-title":"Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients","volume":"161","author":"S Janno","year":"2004","journal-title":"American Journal of Psychiatry"},{"issue":"1","key":"pone.0257129.ref013","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ncl.2010.10.002","article-title":"Movement disorders induced by antipsychotic drugs: implications of the CATIE schizophrenia trial","volume":"29","author":"SN Caroff","year":"2011","journal-title":"Neurologic clinics"},{"issue":"2","key":"pone.0257129.ref014","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/YCO.0b013e3282f53132","article-title":"Tardive dyskinesia and new antipsychotics","volume":"21","author":"CU Correll","year":"2008","journal-title":"Current opinion in psychiatry"},{"issue":"1","key":"pone.0257129.ref015","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/YCO.0b013e3283413505","article-title":"Second-generation antipsychotics in major depressive disorder: update and clinical perspective","volume":"24","author":"J Chen","year":"2011","journal-title":"Current opinion in psychiatry"},{"issue":"4","key":"pone.0257129.ref016","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/WNF.0000000000000040","article-title":"Antipsychotics-induced tardive syndrome: a retrospective epidemiological study","volume":"37","author":"M-J Lee","year":"2014","journal-title":"Clinical neuropharmacology"},{"issue":"9","key":"pone.0257129.ref017","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1517\/14656566.9.9.1451","article-title":"Antipsychotic-induced extrapyramidal symptoms and their management","volume":"9","author":"P Dayalu","year":"2008","journal-title":"Expert opinion on pharmacotherapy"},{"issue":"9657","key":"pone.0257129.ref018","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(08)61764-X","article-title":"Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis","volume":"373","author":"S Leucht","year":"2009","journal-title":"The Lancet"},{"issue":"7","key":"pone.0257129.ref019","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"D Moher","year":"2009","journal-title":"PLoS med"},{"key":"pone.0257129.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"D Moher","year":"2015","journal-title":"Systematic reviews"},{"key":"pone.0257129.ref021","unstructured":"JBI. Joanna Briggs institute, 2017 Critical Appraisal tools. The University of Adelaide, Australia. https:\/\/joannabriggs.org\/critical-appraisal-tools. Accessed on 15 May, 2020."},{"issue":"5","key":"pone.0257129.ref022","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1093\/ije\/dyn065","article-title":"Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation","volume":"37","author":"NA Patsopoulos","year":"2008","journal-title":"International journal of epidemiology"},{"issue":"7109","key":"pone.0257129.ref023","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"M Egger","year":"1997","journal-title":"BMJ (Clinical research ed)"},{"issue":"4","key":"pone.0257129.ref024","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"CB Begg","year":"1994","journal-title":"Biometrics"},{"issue":"7","key":"pone.0257129.ref025","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00787-006-0544-5","article-title":"Prevalence of movement disorders in adolescent patients with schizophrenia and in relationship to predominantly atypical antipsychotic treatment","volume":"15","author":"S Gebhardt","year":"2006","journal-title":"European child & adolescent psychiatry"},{"key":"pone.0257129.ref026","doi-asserted-by":"crossref","first-page":"S1011","DOI":"10.1016\/S0924-9338(09)71244-1","article-title":"P03-12 Prevalence of extrapyramidal side effects in patients receiving depot antipsychotic medication","volume":"24","author":"B Luft","year":"2009","journal-title":"European Psychiatry"},{"issue":"1","key":"pone.0257129.ref027","doi-asserted-by":"crossref","DOI":"10.4088\/JCP.18m12246","article-title":"Prevalence of and Risk Factors for Extrapyramidal Side Effects of Antipsychotics: Results From the National FACE-SZ Cohort","volume":"80","author":"D Misdrahi","year":"2019","journal-title":"The Journal of clinical psychiatry"},{"issue":"3","key":"pone.0257129.ref028","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0920-9964(99)00133-4","article-title":"Prevalence of extrapyramidal syndromes in psychiatric inpatients and the relationship of clozapine treatment to tardive dyskinesia","volume":"42","author":"J Modestin","year":"2000","journal-title":"Schizophrenia research"},{"issue":"3","key":"pone.0257129.ref029","first-page":"114","article-title":"Prevalence of extrapyramidal effects by neuroleptics in admitted people with schizophrenia","volume":"23","author":"M Moreno-Calvete","year":"2013","journal-title":"Enfermeria clinica"},{"issue":"2","key":"pone.0257129.ref030","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/13651501.2017.1381268","article-title":"Prevalence and pattern of antipsychotic induced movement disorders in a tertiary care teaching hospital in India\u2013a cross-sectional study","volume":"22","author":"N Desai","year":"2018","journal-title":"International journal of psychiatry in clinical practice"},{"issue":"3","key":"pone.0257129.ref031","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/00131746-200405000-00011","article-title":"Prophylaxis of antipsychotic-induced extrapyramidal side effects in east Indians: cultural practice or biological necessity?","volume":"10","author":"HS Dhavale","year":"2004","journal-title":"Journal of psychiatric practice"},{"issue":"9","key":"pone.0257129.ref032","first-page":"703","article-title":"Extrapyramidal Side Effects of Intramuscular Antipsychotics in Psychosis and Substance Use Disorders, Occurrence and Predictive Factors","volume":"14","author":"D DUANGRITHI","year":"2017","journal-title":"Walailak Journal of Science and Technology (WJST)"},{"issue":"3","key":"pone.0257129.ref033","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.4088\/JCP.16m11049","article-title":"Effect of Antipsychotic Type and Dose Changes on Tardive Dyskinesia and Parkinsonism Severity in Patients With a Serious Mental Illness: The Cura\u00e7ao Extrapyramidal Syndromes Study XII","volume":"78","author":"CL Mentzel","year":"2017","journal-title":"The Journal of clinical psychiatry"},{"key":"pone.0257129.ref034","first-page":"509","article-title":"Extrapyramidal side effects of risperidone in Iranian schizophrenic patients","volume":"3","author":"M Ghoreishizadeh","year":"2008","journal-title":"Res Biol Sci"},{"issue":"5","key":"pone.0257129.ref035","doi-asserted-by":"crossref","first-page":"76","DOI":"10.11648\/j.ajpn.20140205.12","article-title":"Antipsychotic medication induced movement disorders: the case of Amanuel specialized mental hospital, Addis Ababa, Ethiopia","volume":"2","author":"H Taye","year":"2014","journal-title":"Am J Psychiatry Neurosci"},{"key":"pone.0257129.ref036","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fpsyt.2018.00172","article-title":"Neurological Soft Signs, Spontaneous and Treatment Emergent Extrapyramidal Syndromes in Black Africans With First Episode Schizophrenia","volume":"9","author":"A Ojagbemi","year":"2018","journal-title":"Frontiers in psychiatry"},{"key":"pone.0257129.ref037","author":"AAd Ara\u00fajo","year":"2016","journal-title":"Factors associated with expression of extrapyramidal symptoms in users of atypical antipsychotics"},{"issue":"6","key":"pone.0257129.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0216044","article-title":"Tardive dyskinesia among patients using antipsychotic medications in customary clinical care in the United States","volume":"14","author":"AM Loughlin","year":"2019","journal-title":"PloS one"},{"issue":"5","key":"pone.0257129.ref039","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1192\/bjp.154.5.672","article-title":"A rating scale for drug-induced akathisia","volume":"154","author":"TR Barnes","year":"1989","journal-title":"Br J Psychiatry"},{"issue":"S212","key":"pone.0257129.ref040","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-0447.1970.tb02066.x","article-title":"A rating scale for extrapyramidal side effects","volume":"45","author":"G Simpson","year":"1970","journal-title":"Acta Psychiatrica Scandinavica"},{"issue":"1","key":"pone.0257129.ref041","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/mds.870090112","article-title":"Unified Parkinson\u2019s disease rating scale characteristics and structure","volume":"9","author":"P Mart\u00ednez\u2010Mart\u00edn","year":"1994","journal-title":"Movement disorders"},{"key":"pone.0257129.ref042","first-page":"781","article-title":"Abnormal Involuntary Movement Scale (AIMS)","volume":"24","author":"AIM Scale","year":"1988","journal-title":"Psychopharmacol Bull"},{"key":"pone.0257129.ref043","first-page":"5","article-title":"An overview of side effects caused by typical antipsychotics","volume":"61","author":"GW Arana","year":"2000","journal-title":"The Journal of Clinical Psychiatry"},{"issue":"2","key":"pone.0257129.ref044","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0006-8993(76)90192-X","article-title":"The projections of the A8, A9 and A10 dopaminergic cell bodies: evidence for a nigral-hypothalamic-median eminence dopaminergic pathway","volume":"108","author":"J Kizer","year":"1976","journal-title":"Brain research"},{"issue":"1","key":"pone.0257129.ref045","first-page":"119","article-title":"Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects","volume":"53","author":"PG Strange","year":"2001","journal-title":"ASPET Pharmacological Reviews"},{"issue":"9","key":"pone.0257129.ref046","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1517\/14656566.9.9.1451","article-title":"Antipsychotic-induced extrapyramidal symptoms and their management","volume":"9","author":"P Dayalu","year":"2008","journal-title":"Expert Opin Pharmacother"},{"issue":"3","key":"pone.0257129.ref047","first-page":"320","article-title":"Distribution of the mRNA encoding the four dopamine D1 receptor subtypes in the brain of the European eel (Anguilla anguilla): comparative approach to the function of D1 receptors in vertebrates","volume":"419","author":"M Kapsimali","year":"2000","journal-title":"JCN"},{"key":"pone.0257129.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40263-019-00625-3","article-title":"Medication-induced akathisia with newly approved antipsychotics in patients with a severe mental illness: a systematic review and meta-analysis","volume":"33","author":"K Demyttenaere","year":"2019","journal-title":"CNS Drugs"},{"issue":"12","key":"pone.0257129.ref049","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S1474-4422(05)70226-X","article-title":"Prevalence of movement disorders in men and women aged 50\u201389 years (Bruneck Study cohort): a population-based study","volume":"4","author":"GK Wenning","year":"2005","journal-title":"Lancet Neurology"},{"issue":"3","key":"pone.0257129.ref050","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1176\/appi.ajp.161.3.414","article-title":"Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies","volume":"161","author":"CU Correll","year":"2004","journal-title":"AM J Psychiatry"},{"issue":"3","key":"pone.0257129.ref051","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/YCO.0000000000000491","article-title":"Antipsychotic-induced tardive dyskinesia: update on epidemiology and management","volume":"32","author":"CG Widschwendter","year":"2019","journal-title":"Current opinion in psychiatry"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0257129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T13:28:32Z","timestamp":1631280512000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0257129"}},"subtitle":[],"editor":[{"given":"Xenia","family":"Gonda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,9,10]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0257129","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,10]]}}}