Case ReportsCase report: asenapine and anticholinergic toxicitySheehan, Ann Kathleena,,b; Richards-Bentley, Christophera,,c; Hawa, Raed J.a,,b; Rasimas, Joseph J.d,,eAuthor Information aDepartment of Psychiatry, University of Toronto bUniversity Health Network Centre for Mental Health cCentre for Addiction and Mental Health, Toronto, Ontario, Canada dDepartment of Psychiatry, University of Minnesota eHennepin Healthcare, Minneapolis, Minnesota, USA Received 16 September 2020 Accepted 16 March 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.intclinpsychopharm.com Correspondence to Kathleen Sheehan, MD, DPhil, Toronto General Hospital – University Health Network, 200 Elizabeth Street, 8EN-Rm 231, Toronto, ON M5T 1L8, Canada, Tel: +4163403747; e-mail: [email protected] International Clinical Psychopharmacology: July 2021 - Volume 36 - Issue 4 - p 214-217 doi: 10.1097/YIC.0000000000000360 Buy SDC Metrics Abstract While antipsychotic medications have long been associated with anticholinergic effects, asenapine has been purported to have no capacity for muscarinic cholinergic antagonism based on in vitro studies. Research in rat brain tissue has yielded different results, with one study finding more cholinergic M1-5 binding in the medial prefrontal cortex, dorsolateral frontal cortex and hippocampal CA1 and CA3 areas than would be predicted from in vitro findings. Moreover, it is structurally similar to other anticholinergic antipsychotics such as loxapine and, to a lesser degree, quetiapine, olanzapine and clozapine. This case report describes the anticholinergic toxidrome in a patient treated with benztropine and paroxetine at stable doses, with the emergence of the toxidrome after upward titration of asenapine. A broad differential was considered. With further consideration of the history, time-course, clinical features and physical examination, the presentation is most indicative of the anticholinergic toxidrome. Although not employed, physostigmine, the antidote for anticholinergic delirium, could help to differentiate this toxidrome and serve as a diagnostic and therapeutic intervention. We have presented this case to highlight the importance for clinicians to integrate history and bedside examination data with principles of pharmacology. In particular, asenapine should be added to the list of compounds with recognized anticholinergic potential. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.