Ecopipam Shows Promise in Tourette Syndrome: Phase 3 Trial Highlights Sustained Tic Control
USA: A phase 3 randomized clinical trial published in JAMA Neurology has found that ecopipam, a selective dopamine D1 receptor antagonist, may offer a promising and well-tolerated treatment option for individuals with Tourette syndrome (TS), particularly in children and adolescents.
Tourette syndrome is often challenging to manage due to the limitations of currently available medications, many of which are associated with adverse effects and high discontinuation rates. Against this backdrop, researchers led by Donald L. Gilbert from Cincinnati Children’s Hospital Medical Center evaluated the safety and sustained efficacy of ecopipam over a 24-week treatment period.
The trial was conducted across 77 sites in 12 countries between January 2023 and February 2025 and included participants aged 6 years and older diagnosed with TS. The study design consisted of an initial 12-week open-label phase, during which all participants received ecopipam, followed by a 12-week double-blind randomized withdrawal phase. During the open-label period, the drug was gradually titrated to a target dose of 1.8 mg/kg per day.
Participants who showed a clinically meaningful response—defined as at least a 25% reduction in tic severity scores at both weeks 8 and 12—were then randomized either to continue ecopipam or switch to placebo. The primary outcome assessed was the time to relapse, defined as a significant loss of the initial improvement in tic severity.
The trial revealed the following findings:
- A total of 216 participants entered the open-label phase, with the majority being pediatric patients.
- Among responders who were randomized, ecopipam significantly improved maintenance of tic control in children and adolescents.
- Pediatric participants continuing ecopipam had a markedly lower risk of relapse compared to those switched to placebo.
- Adults showed a similar trend toward reduced relapse risk, although the results were not statistically significant, likely due to the small sample size.
- Ecopipam was generally well tolerated across both study phases.
- The most commonly reported adverse events were somnolence, anxiety, headache, insomnia, and fatigue.
- No clinically meaningful weight gain was observed with ecopipam treatment.
- The drug did not lead to adverse metabolic effects.
- No cases of drug-induced movement disorders were reported.
- Overall, the safety profile suggests fewer limitations compared to existing therapies for Tourette syndrome.
The findings indicate that ecopipam can both achieve and maintain meaningful reductions in tic severity for up to 24 weeks, with a favorable safety profile and a novel mechanism supporting its potential as an alternative treatment for Tourette syndrome across age groups.
However, limitations such as limited participant diversity, a small adult sample, and the constraints of a randomized withdrawal design should be considered, as the study primarily assessed maintenance of response rather than overall treatment effect.
Overall, the results highlight dopamine D1 receptor targeting as a promising new therapeutic approach, offering potential for improved long-term management with fewer adverse effects.
Reference:
Gilbert DL, Atkinson SD, Kim DJB, et al. Efficacy and Safety of Ecopipam for Tourette Syndrome: A Phase 3 Randomized Clinical Trial. JAMA Neurol. Published online May 26, 2026. doi:10.1001/jamaneurol.2026.1431
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