Objective: To report a possible association between high dose amantadine and increased falling in patients with Parkinson’s disease (PD).

Background: Amantadine is used in PD as an antiparkinson and antidyskinetic agent. Amantadine toxicity is associated with psychiatric symptoms, but myoclonus may occur as well. No association between amantadine toxicity and increased fall risk has been reported.

Method: Case report, medical chart review, literature review.

Results: The patient is a 55 year old man with a 13 year history of tremor predominant PD. Because of LD intolerance he received DBS 5 yrs after disease onset with 300 mg amantadine/day for many years and 400 mg/day for the last 2 years. He tolerated this without any psychiatric symptoms. He was doing well except for multiple falls/day for the last 5 years. He then presented with acute onset of confusion, hallucinations and paranoid delusions. On initial exam he followed simple commands but then became non-communicative. Generalized myoclonus was present. He had a normal CBC, diff, and UA. His BUN/Creat was 40/1.96. Amantadine was discontinued while a work-up was initiated to rule other potential causes. After 3 days he started speaking again, but nonsensically and expressing delusional thoughts. Agitation required 4-point restraints and lorazepam. After 1 week the myoclonus resolved but confusion and paranoid ideation continued. Speech consisted of actual words strung together in incoherent fashion, and insight, judgement, memory remained impaired. UN/Creat normalized. After 2 weeks he answered and asked appropriate questions, but some confusion, hallucinations and nonsensical statements persisted. He then rapidly returned to baseline and was discharged on Day 17. In follow-up he reported his walking was better than it had been in years. He no longer needed a cane or hold onto walls. At last follow-up 2 years after discharge he still had not fallen.

Conclusion: This patient went from falling several times/day to not falling at all. The falling started years before the psychosis that prompted cessation of amantadine. No other medications were changed to explain the improvement in balance. We propose that dysbalance can be an early sign of amantadine toxicity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/high-dose-amantadine-therapy-may-cause-increased-falling-in-parkinsons-patients/