JAMA Neurol
Promising Tourette therapy delivers sustained tic reduction
Clinical Takeaway: Consider ecopipam as a potential future option for patients with Tourette syndrome who respond to therapy but need durable control with a favorable safety profile, particularly when concerns about metabolic or extrapyramidal effects limit current treatments.
Current pharmacologic treatments for Tourette syndrome are often limited by weight gain, metabolic effects, sedation, and movement disorders. Ecopipam, a selective dopamine D1 receptor antagonist, could offer a new option with a more favorable tolerability profile.
In this phase 3 randomized withdrawal trial, investigators evaluated ecopipam in 216 patients aged 6 years and older with Tourette syndrome across 77 sites in 12 countries. After a 12-week open-label treatment period, 104 responders were randomized to continue ecopipam or taper to placebo for an additional 12 weeks.
Among pediatric participants, ecopipam significantly reduced relapse risk compared with placebo (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.26-0.84; P=.008). Relapse occurred in 41.9% of patients continuing ecopipam versus 68.1% receiving placebo. In the overall study population, relapse rates were 41.2% with ecopipam and 67.9% with placebo (HR 0.47; P=.005). Mean Yale Global Tic Severity Scale Total Tic Score improved by 47.5% during open-label treatment in pediatric patients.
The most common adverse events included somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), and fatigue (6.5%). Most events were mild to moderate, and no clinically meaningful changes were seen in BMI, lipids, glucose parameters, prolactin, or ECG findings.
“Ecopipam maintained clinically meaningful TS symptom improvements and was well tolerated for up to 24 weeks,” the authors wrote. They also noted the absence of “clinically relevant weight gain, adverse metabolic effects, or drug-induced movement disorders.”
Source: Gilbert DL, et al. (2026, May 26). JAMA Neurol. Efficacy and Safety of Ecopipam for Tourette Syndrome: A Phase 3 Randomized Clinical Trial