Amantadine for freezing of gait in patients with Parkinson disease

Abstract

Background: Freezing of gait (FOG) is a common symptom in patients with advanced Parkinson's disease (PD) representing a major cause of disability and falls. Although the pathophysiology of FOG remains poorly understood, nondopaminergic pathways have been implicated. Treatment studies of levodopa and selegiline have shown limited benefit for FOG. Limited data suggest that amantadine, an N-methyl-D-aspartate receptor antagonist, may be beneficial for FOG in PD.

Objective: To examine the relationship between treatment with oral amantadine and FOG in patients with PD.

Methods: We conducted a retrospective chart review of PD patients who received amantadine specifically for FOG and had a follow-up assessment of FOG. The primary outcome measure was self-reported effectiveness of amantadine (improvement, worsening, or no change in FOG) based on records from the follow-up assessment.

Results: Eleven patients with PD with median age of PD onset of 67 years (range, 51-84 years) and median Hoehn and Yahr stage 3 (range, 2-4) met the study population selection criteria. Ten of 11 patients reported improvement in FOG after initiation of amantadine, whereas FOG worsened in one patient. Median amantadine dosage was 100 mg twice daily, and treatment duration was 20 months (range, 6-66 months). Four patients reported reduction in benefit after 4 months. Three patients reported adverse effects, including blurred vision, visual hallucinations, and peripheral edema; the latter 2 effects resulted in discontinuation of amantadine.

Conclusion: Amantadine is associated with self-reported improvement in FOG in PD, but this effect may be transient. Further studies, including a randomized placebo-controlled trial, are needed to better evaluate this association.