Exploratory cross-over, trial of augmented RLS with the dopamine receptor 1/5 antagonist ecopipam D1/D5 antagonist ecopipam for augmented RLS

Abstract

Background

Restless legs syndrome (RLS) is a common condition that initially responds dramatically to dopaminergic therapy. Over time, however, dopaminergics cause augmentation, where symptoms occur earlier and intensify. Animal models suggest this may result from increased dopamine receptor type-1 affinity in the spinal cord. Ecopipam is a potent, specific dopamine-1/5 receptor antagonist.

Methods

We performed a small (N = 10) exploratory placebo controlled, cross-over safety trial of ecopipam (25–100 mg/day) for patients with augmented RLS currently taking dopamine agonists.

Results

Ecopipam was well tolerated with sedation being the most common adverse event in drug and placebo. Safety scales and serology data were similar to placebo. The study was not powered to demonstrate efficacy and exploratory efficacy data showed no significant improvement compared to placebo, but RLS diaries, the international RLS rating scale, and clinical global impressions all favored drug. No subject worsened on drug or demonstrated rebound worsening after drug discontinuation.

Conclusion

Ecopipam was safe and well tolerated in this initial study for RLS. Given the lack of alternate options, larger efficacy studies for augmented RLS, and potentially de novo RLS are justified.

Keywords:

• Ecopipam
• D1 antagonist
• restless legs syndrome
• augmentation
• clinical trial

Acknowledgement

We would like to acknowledge the assistance of Richard Chipkin PhD in obtaining the study drug and for his background knowledge on ecopipam.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Grant from the Restless Legs Syndrome Foundation.