{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:35:35Z","timestamp":1778250935011,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T00:00:00Z","timestamp":1381449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec><jats:title>Study Objectives<\/jats:title><jats:p>Case reports suggest a relationship between cholinesterase inhibitors (Ch<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>s) and Pisa syndrome (<jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content>), also known as pleurothotonus, a form of dystonia, but this relationship has not been systematically examined. Our objective was to estimate the adjusted reporting ratios of <jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content> with donepezil, rivastigmine, and galantamine in the United States Food and Drug Administration (<jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content>) Adverse Event Reporting System (<jats:styled-content style=\"fixed-case\">FAERS<\/jats:styled-content>) database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective analysis of adverse event reports in the <jats:styled-content style=\"fixed-case\">FAERS<\/jats:styled-content> database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Patients with drug\u2010related adverse events in the <jats:styled-content style=\"fixed-case\">FAERS<\/jats:styled-content> database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>The Gamma Poisson Shrinker algorithm was used to estimate the empirical Bayes geometric mean (<jats:styled-content style=\"fixed-case\">EBGM<\/jats:styled-content>) along with the lower and upper 90% confidence interval (CI) limits (<jats:styled-content style=\"fixed-case\">EB<\/jats:styled-content>05 and <jats:styled-content style=\"fixed-case\">EB<\/jats:styled-content>95, respectively), as measures of the adjusted reporting ratio of PS in patients taking <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">EB<\/jats:styled-content>05\u00a0&gt;\u00a02.0 was used as the cutoff for significance for the signals. The <jats:styled-content style=\"fixed-case\">EBGM<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">EB<\/jats:styled-content>05) was 37.9 (30) for all <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">EIs<\/jats:styled-content>, 25.6 (17.6) for donepezil, 76.4 (50.3) for galantamine, and 33.7 (21.2) for rivastigmine. All adverse event signals were strongly significant based on the a priori set <jats:styled-content style=\"fixed-case\">EB<\/jats:styled-content>05 cutoff. The female:male ratio in the reported cases was 2:1. No significant signals were found between Ch<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>s and other dystonias. About half of the Ch<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> users were also taking concomitant antipsychotics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although FAERS data cannot establish causality due to reporting biases, our findings support a potential dopaminergic\u2010cholinergic imbalance as an underlying mechanism for PS and may help increase clinician awareness, early identification, and treatment of <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>h<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>\u2010related dystonias.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1359","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T07:21:24Z","timestamp":1381735284000},"page":"272-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Cholinesterase Inhibitors and Pisa Syndrome: A Pharmacovigilance Study"],"prefix":"10.1002","volume":"34","author":[{"given":"Anthony S.","family":"Zannas","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Okuno","sequence":"additional","affiliation":[{"name":"Department of Systems Biosciences for Drug Discovery Graduate School of Pharmaceutical Sciences Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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