Acute delirium after withdrawal of amantadine in Parkinson's disease

We present three patients who, after long-term therapy with amantadine (4 to 18 years), experienced an acute delirium with confusion, disorientation, agitation, and paranoia on withdrawal. These patients had Parkinson's disease for 5 to 29 years; mean age was 73 years. All had a history of varying degrees of dementia and transient hallucinations in the past. Adjustment of other medications was ineffective in improving their condition and no other cause was found. Only with reinstitution of amantadine did the patients return to baseline status (usually within days).