Sustained Antidyskinetic Effect of Amantadine in Levodopa-treated Patients with Advanced Parkinson's Disease

21 Mar, 22

Introduction

Results of several randomized placebo-controlled trials have consistently demonstrated the antidyskinetic effects of amantadine in levodopa-treated patients with advanced Parkinson's disease (PD). Nevertheless, all the trials were of short duration. Moreover, studies have also claimed that the effect of amantadine on levodopa induced dyskinesias (LID's) wear off after about 9 months of treatment.

Aim

To determine the long-term antidyskinetic effect of amantadine in PD patients, maintained on stable amantadine therapy for LID over at least one year

Patient Profile

Patients with idiopathic PD and motor complications, who were maintained on stable amantadine therapy for LID over at least one year (n=32)

Methods

Study Design

A randomized placebo-controlled, double-blind parallel-group study

Treatment Strategy

Study subjects were randomized 1:1 to amantadine or placebo and followed for 3 weeks

Assessments

Dyskinesia duration and intensity were assessed using UPDRS IV items 32 and 33 as well as by patient's diaries.

Outcomes

Primary Outcome

The score changes for UPDRS IV items 32 + 33 between baseline and 3 weeks after treatment

Secondary Outcomes

Daily duration of ON time with troublesome dyskinesias
ON time with non-troublesome dyskinesias
ON time without dyskinesias
Total daily OFF time

Results

At 3 weeks, the UPDRS IV items 32 + 33 scored increased significantly in patients treated with placebo (p=0.02) but not in patients treated with amantadine (Fig. 1)

Fig. 1: Changes in the UPDRS score during the study

The ON time with troublesome dyskinesia and the duration of dyskinesia increased significantly from baseline to week 3 in placebo group, there was no significant change in the patients treated with amantadine (Table 1).

Table 1: Changes in the secondary outcomes during the study

Secondary Outcome	Amantadine Group			Placebo Group
Secondary Outcome	Baseline	End of the study	Difference	Baseline	End of the study	Difference
ON time without dyskinesia	5.5	5.4	-0.05	6.3	4.9	-0.86
ON time with non-troublesome dyskinesia	4.6	4.2	-0.3	3.5	2.7	-1.0
ON time with troublesome dyskinesia	2.8	2.5	-0.2	1.7	3.5	1.8
OFF Time	3.0	2.8	-0.1	2.9	3.6	0.6

Conclusions

The findings of the study support a sustained antidyskinetic effect of amantadine extending well beyond one year of therapy, for the treatment of LID’s in PD patients.
Clinicians should consider that discontinuation of amantadine treatment may increase dyskinesia severity and duration in PD patients.

Mov Disord. 2010 Jul 30;25(10):1357-63.