Session Information
Date: Monday, September 23, 2019
Session Title: Restless Leg Syndrome, RBD and Other Sleep Disorders
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To establish initial safety and preliminary efficacy of ecopipam, a D1 specific antagonist in patients currently taking dopamine agonist and demonstrating augmentation.
Background: Dopamine agonists (DA) initially dramatically improve restless legs syndrome (RLS), however long-term treatment often results in augmentation, where the baseline RLS intensity markedly worsens. There is no established strategy aside from DA discontinuation, which is extremely difficult. D2 antagonists typically worsen RLS. Based on animal studies, upregulation of dopamine type 1 receptors in the spinal cord is hypothesized to account for augmentation. We tested the safety and explored efficacy of ecopipam, the only D1 specific antagonist (DA), in a population of RLS patients with dopamine agonist induced augmentation.
Method: This is an exploratory controlled 6 week/arm, 2 week wash-out, cross-over trial of ecopipam (25mg-100mg) vs. placebo. Patients continued their dopamine agonists. Ecopipam tolerability was primary. Efficacy assessments included the IRLS, RLS diaries, and clinical global impressions.
Results: 9/10 subjects completed the trial, 1 dropped for logistical reasons after the first leg, which was active drug. Tolerability was very good. The most common adverse event was sedation (5 drug vs 3 placebo). There was no rebound exacerbation after ecopipam discontinuation and no one report RLS exacerbation. Efficacy results were complicated by a carry-over effect and placebo response. CGI favored active drug 3.30 vs 3.94, but did not correlate with IRLS scores, which were not significantly different, and showed very high variance. Three- day RLS diary data favored active drug (10.2 hours vs. 15.0 hours), p=0.2.
Conclusion: Ecopipam was well tolerated and demonstrated encouraging preliminary efficacy results in augmented RLS patients. Larger trials in augmented RLS, and potentially de novo RLS, are warranted.
To cite this abstract in AMA style:
O. Titlayo, W. Ondo. Treatment of dopaminergic augmented RLS with Ecopipam, A D1 specific antagonist: an exploratory placebo controlled cross-over trial [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/treatment-of-dopaminergic-augmented-rls-with-ecopipam-a-d1-specific-antagonist-an-exploratory-placebo-controlled-cross-over-trial/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/treatment-of-dopaminergic-augmented-rls-with-ecopipam-a-d1-specific-antagonist-an-exploratory-placebo-controlled-cross-over-trial/