Case report: asenapine and anticholinergic toxicity

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.