The Use of Physostigmine in the Diagnosis and Treatment of Anticholinergic Toxicity Following Olanzapine Overdose: Literature Review and Case Report

Abstract Second generation antipsychotic agents are commonly used by clinicians for the treatment of various psychiatric and medical conditions. Despite their presumed safety, an overdose with olanzapine may lead to the development of anticholinergic toxicity. The anticholinergic toxidrome is characterized by both central and peripheral physical findings. Central Anticholinergic Syndrome (CAS), a term used to describe the symptoms that arise from reduced cholinergic activity in the central nervous system, is characterized primarily by signs and symptoms consistent with hyperactive delirium. Signs of peripheral anticholinergia include mydriasis and blurred vision, tremors, ataxia, fever/hyperthermia, flushed and dry skin, dry oral mucosa, decreased bowel sounds, constipation, and urinary retention, among other symptoms. In extreme cases, CAS can be associated with seizures, coma, respiratory failure, and cardiovascular collapse. Currently the recommended treatment for olanzapine overdose, as is the case of most cases of severe anticholinergic toxicity, involves supportive care, along with cardiac, neurological and respiratory status monitoring. In this manuscript we detail the symptoms characteristic of anticholinergic toxicity, using the case of a patient experiencing CAS after an overdose with olanzapine. We also provide a comprehensive review of the published literature on the symptoms, diagnosis and treatment of anticholinergic toxicity. We specifically review the use of physostigmine, a tertiary acetylcholinesterase inhibitor, to assist in the diagnosis and management of severe anticholinergic toxicity associated with an olanzapine overdose, but which might be applicable to the antimuscarinic toxidrome associated with the ingestion of agents with significant anticholinergic activity.