Introduction

Amantadine, a N-methyl-D-aspartate receptor antagonist, is frequently used in combination with levodopa for symptomatic relief in Parkinson's disease (PD) patients with levodopa-induced dyskinesia (LID). However, there is a lack of real-world evidence regarding the use of amantadine for lowering the risk of LID in patients with PD

Aim

To evaluate the association between early amantadine treatment and LID onset in patients with early-stage PD

Patient Profile

• 1526 PD patients with LID who were new users of amantadine, anticholinergics, and monoamine oxidase type B inhibitors (MAOBIs)

Method

Study Design

• Hospital-based retrospective cohort study
• The effect of amantadine on LID onset was compared with those of anticholinergics and monoamine oxidase type B inhibitors

Endpoints

• Delay in onset of LID

Results

Efficacy

• Amantadine use was associated with significantly delayed LID onset in the 6-and 12-month landmark analyses as compared with the comparator groups (adjusted hazard ratios 0.65, p < 0.01 and 0.64, p < 0.01, respectively)
• Sensitivity analysis findings were comparable to those of the main analysis
• Amantadine was associated with significantly lower risk of LID in the 6-and 12-month landmark analyses in patients whose time to referral was <1 year and had an incomplete history of dopaminergic drug exposure
• Amantadine use was associated with significantly delayed LID onset in the 18-month landmark analysis as compared to MAOBIs (aHR = 0.50, p < 0.01)
• Amantadine treatment significantly reduced the risk of LID in the 6-and 12-month landmark analyses among patients >50 years at PD onset

Conclusion

• Early treatment with amantadine significantly delayed the onset of LID more than other symptomatic agents (anticholinergics or monoamine oxidase type B inhibitors) in patients with early PD
• This was the first observational study that used longitudinal data to evaluate the effect of early amantadine treatment on LID

Eur J Neurol. 2022; 29: 1044–1055