Abstract
INTRODUCTION: This systematic review and meta-analysis investigated the long-term efficacy of Amantadine for Levodopa-induced dyskinesia (LID) in Parkinson's disease patients. Our analysis focused on longer-term motor outcomes, including those which are under-reported in the literature. METHODS: We identified relevant articles by searching four online databases and reviewing citations. The primary outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS) or Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV and daily "ON" time; secondary outcomes included UPDRS/MDS-UPDRS III and IVa, Unified Dyskinesia Rating Scale (UDysRS) total score, and daily "OFF" time. For each outcome, we conducted meta-analyses for numerous time-points after beginning treatment: "up to 13 weeks", "up to 16 weeks", "12 to 16 weeks", and "38 to 101 weeks". Our outcome measure was the Standardized Mean Differences (SMDs) between the pooled Amantadine-Levodopa and Levodopa only (control) groups. RESULTS: We found associations between Amantadine and each motor outcome. The most considerable was an SMD of -0.73 points for Amantadine compared to control for the UPDRS/MDS-UPDRS IV at up to 16 weeks after beginning treatment (P < 0.0001). However, the magnitude of most associations decreased with time, indicating declining long-term efficacy. We also identified a risk of added "adverseness"; 11 studies had patient-reported adverse events, mainly overlaid with known symptoms. CONCLUSION: Our findings suggest that Amantadine is an effective adjunct medication for improving LID and broader Parkinson's disease symptoms. However, evidence of its declining long-term efficacy and "adverseness" have important implications for its use in Parkinson's disease therapy.