Amantadine withdrawal syndrome masquerading as COVID-19 encephalopathy: a case report and review of the literature

Amantadine withdrawal syndrome (AWS) is a rare but recognized cause of severe and persistent altered mental status sometimes with co-occurring extrapyramidal symptoms. First described in a case series from 1987, its clinical manifestations have been characterized along a spectrum ranging from profound hypoactive delirium to hyperactive delirium with hallucinations. Risk factors for withdrawal include abrupt medication discontinuation, prolonged use, older age and underlying dementia. Herein we describe a case of a 52-year-old woman who presented with confusion, hallucinations, and coronavirus disease-2019 infection. She subsequently developed a prolonged hypoactive delirium after her amantadine was tapered and held. Her hypoactive delirium entirely resolved with resumption of amantadine confirming the diagnosis of AWS. This case illustrates the importance of slowly tapering dopaminergic medications and being aware of rare pharmacologic side effects.