TY - JOUR
T1 - Exploratory cross-over, trial of augmented RLS with the dopamine receptor 1/5 antagonist ecopipam D1/D5 antagonist ecopipam for augmented RLS
AU - Ondo, William G.
AU - Olubajo, Titilayo
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - D1 antagonist
KW - Ecopipam
KW - augmentation
KW - clinical trial
KW - restless legs syndrome
UR - http://www.scopus.com/inward/record.url?scp=85094655260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85094655260&partnerID=8YFLogxK
U2 - 10.1080/00207454.2020.1838515
DO - 10.1080/00207454.2020.1838515
M3 - Article
C2 - 33066723
AN - SCOPUS:85094655260
JO - International Journal of Neuroscience
JF - International Journal of Neuroscience
SN - 0020-7454
ER -