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.
Subject(s)
Amantadine/therapeutic use , Gait Disorders, Neurologic/drug therapy , Gait Disorders, Neurologic/epidemiology , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Aged , Aged, 80 and over , Antiparkinson Agents/therapeutic use , Cohort Studies , Female , Follow-Up Studies , Gait Disorders, Neurologic/etiology , Humans , Male , Middle Aged , Parkinson Disease/complications , Retrospective StudiesABSTRACT
Recent data suggests that isradipine, a dihydropyridine calcium channel blocker, is neuroprotective in preclinical models of parkinsonism. Isradipine has not been systematically studied in patients with Parkinson's disease (PD). The aim of this study was to evaluate safety and tolerability of isradipine controlled release (CR) in patients with early PD. Qualified subjects (n = 31) received isradipine CR, titrated from 5 to 20 mg daily dose over 8 weeks as tolerated. Eighty-one percent of subjects completed the study. Tolerability of isradipine CR was dose dependent: 94% for 5 mg dose; 87% for 10 mg; 68% for 15 mg; and 52% for 20 mg. Isradipine had no significant effect on blood pressure or PD motor disability. The two most common reasons for dose reduction were leg edema (7) and dizziness (3). There was no difference in isradipine tolerability between subjects with and without dopaminergic treatment, or with and without hypertension.
