# A meta-analysis of the long-term efficacy of Amantadine for Levodopa-induced dyskinesia in Parkinson’s disease

## TL;DR

Amantadine reduces dyskinesia caused by Levodopa in Parkinson’s disease but becomes less effective over time and may cause additional side effects.

## Contribution

This study provides a meta-analysis of Amantadine’s long-term efficacy and safety in Parkinson’s disease patients, highlighting its diminishing effectiveness and increased adverse events.

## Key findings

- Amantadine significantly improves motor outcomes like dyskinesia and 'ON' time in the short term.
- The effectiveness of Amantadine declines over time, with smaller effect sizes observed at longer durations.
- Amantadine therapy is associated with additional adverse events beyond known symptoms.

## Abstract

•Amantadine linked to reduced Levodopa-induced dyskinesia in Parkinson’s disease.•Improvement in numerous motor outcomes in Parkinson’s disease patients.•Prolonged treatment may result in reduced efficacy of Amantadine in the long term.•Risk of adverse events with Amantadine therapy, beyond expected symptoms.

Amantadine linked to reduced Levodopa-induced dyskinesia in Parkinson’s disease.

Improvement in numerous motor outcomes in Parkinson’s disease patients.

Prolonged treatment may result in reduced efficacy of Amantadine in the long term.

Risk of adverse events with Amantadine therapy, beyond expected symptoms.

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.

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.

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.

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.