ECOPIPAM has demonstrated durable benefits as a potential Tourette Syndrome treatment, significantly reducing relapse risk in children and adolescents while maintaining meaningful tic improvements for up to 24 weeks.
Relapse Prevention Remains a Key Challenge
Current pharmacological options for Tourette syndrome are often limited by adverse effects and high discontinuation rates, creating demand for safer long-term approaches. Researchers investigated whether ecopipam could provide sustained benefit as a Tourette Syndrome treatment while maintaining an acceptable safety profile in paediatric and adult populations.
Randomised Withdrawal Design Tests Durability
This phase 3, double-blind, placebo-controlled randomised withdrawal trial enrolled 216 participants aged 6 years and older across 77 sites in 12 countries between January 2023 and February 2025. All participants entered a 12-week open-label ecopipam period, during which treatment was titrated over 3–4 weeks to a target dose of 1.8 mg/kg daily. Responders, defined as achieving at least 25% improvement in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) at Weeks 8 and 12, were randomised to continue ecopipam or taper to placebo for a further 12 weeks. Overall, 167 participants (77.3%) were paediatric, 146 (67.6%) were male, and 70 (32.4%) were female. Primary outcomes assessed time to relapse in participants aged 6–18 years, while adult outcomes were exploratory.
Significant Reduction in Relapse Risk
Among paediatric participants, 43 were randomised to ecopipam and 47 to placebo. Ecopipam significantly reduced relapse risk compared with placebo, with a hazard ratio of 0.47 (95% CI: 0.26–0.84; P=0.008; n=90). Adult participants showed a similar directional effect, although statistical significance was not reached (HR 0.51; 95% CI: 0.11–2.30; P=0.37; n=14). The combined analysis indicated approximately a 50% lower relapse risk with active treatment. Common adverse events included somnolence in 24 participants (11.1%), anxiety in 21 (9.7%), headache in 21 (9.7%), insomnia in 19 (8.8%), tic worsening in 17 (7.9%), and fatigue in 14 (6.5%). No drug-induced movement disorders were reported.
Implications for Future Tourette Syndrome Treatment
The findings suggest ecopipam may offer an effective long-term Tourette Syndrome treatment, particularly for younger patients. Further research is needed to clarify efficacy in adults, but the favourable safety profile and sustained tic control support continued clinical development and potential future use in routine practice.
Reference
Gilbert DL et al. Efficacy and safety of ecopipam for tourette syndrome: a phase 3 randomized clinical trial. JAMA Neurol. DOI:10.1001/jamaneurol.2026.1431.
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