Objective: To investigate the efficacy and safety of the selective dopamine D1 receptor antagonist ecopipam in children and adolescents with Tourette Syndrome (TS).

Background: Dysregulation of dopaminergic signaling has been hypothesized to contribute to tic generation in TS. Dopamine-2 (D2) receptor blocking agents are often efficacious for tics, but side effects such as weight gain limit their use. Based on our open label study of the Dopamine-1 (D1) antagonist ecopipam in adults with TS¹, a double-blind, randomized controlled study was conducted in children/adolescents².

Methods: Forty children ages 7 to 17 years meeting criteria for TS and having a Yale Global Tic Severity Scale (YGTSS) total tic score of ≥ 20 were enrolled in a double-blind, placebo-controlled, crossover study. Participants were prohibited from taking stimulants for ADHD and D2 receptor blocking agents, alpha2 noradrenergic agonists, or other medications for tics during the study. Subjects were randomized to receive either ecopipam (50 mg/day for subjects weighing <34 kg; 100 mg/day for >34 kg) or placebo for 4 weeks, followed by a 2-week washout and then crossed over to the alternative treatment for 4 weeks.  Clinical evaluations were performed at 2 and 4 weeks after the start of each period. The primary outcome measure was tic severity assessed by YGTSS (motor+phonic scores). Clinical Global Impression of Improvement (CGI-I) was the secondary endpoint. Behavioral scales for OCD and ADHD were also performed. Analysis was intent-to-treat. Adverse events were tabulated.

Results: At both the two week and the four week time points, reduction in YGTSS total tics scores was greater for ecopipam treatment compared to placebo (p < .05). At the four week time point, the percentage of patients showing “much” or “very much” improvement was 38% for ecopipam versus 18% for placebo (p = .08).  Adverse events reported for both ecopipam and placebo were rated predominantly mild-to-moderate, with only 4 rated as “severe” and only one serious adverse event (unrelated). There was no weight gain,  drug induced movement disorders, or changes in lab tests, ECGs, or vital signs. Dropout rate was 5%.

Conclusions: This is the first double-blind, placebo controlled study of ecopipam, a D1 receptor antagonist, in children and adolescents with TS. The results showed that it was an efficacious and well-tolerated treatment.

References: 1. Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE. A D1 Receptor Antagonist, Ecopipam, for treatment of tics in Tourette Syndrome. Clinical Neuropharmacology, 2014. 37:26-30.

2. ClinicalTrials.gov Identifier: NCT02102698.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-study-of-the-d1-receptor-antagonist-ecopipam-for-children-and-adolescents-with-tourette-syndrome/