In Tourette Syndrome Trial, Ecopipam Maintained Reductions in Tics
KEY TAKEAWAYS
- Ecopipam significantly reduced relapse risk compared with placebo in pediatric participants with Tourette syndrome who had responded during open-label treatment.
- In the pediatric randomized population, relapse occurred in 41.9% of participants continuing ecopipam and 68.1% of those switched to placebo.
- Ecopipam was not associated with clinically meaningful weight gain, metabolic changes, or drug-induced movement disorders over 24 weeks.
Treatment with ecopipam (Teva Pharmaceuticals, Tel Aviv, Israel), an investigational once-daily selective dopamine D1 receptor antagonist, demonstrated maintained tic reduction in pediatric participants with Tourette syndrome (TS), according to phase 3 randomized clinical trial results published in JAMA Neurology.
The double-blind, placebo-controlled randomized-withdrawal D1AMOND study (NCT05615220) enrolled 216 participants aged 6 years and older across 77 sites in 12 countries. All participants received open-label ecopipam for 12 weeks, titrated to a target dose of 1.8 mg/kg per day. Participants with at least 25% improvement in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) at weeks 8 and 12 were randomized to continue ecopipam or taper to placebo for 12 weeks.
Trial Findings
- Among pediatric responders, ecopipam reduced relapse risk vs placebo (HR, 0.47; 95% CI, 0.26 to 0.84; P=.008).
- Relapse occurred in 18 of 43 pediatric participants receiving ecopipam and 32 of 47 receiving placebo.
- In the overall randomized population, ecopipam also reduced relapse risk (HR, 0.47; 95% CI, 0.28 to 0.81; P=.005).
- The adult subgroup showed a directionally similar but nonsignificant effect, with limited statistical power.
- Common adverse events during ecopipam treatment included somnolence, anxiety, headache, insomnia, tic, and fatigue.
Investigators reported no clinically meaningful changes in body mass index z scores, glycated hemoglobin, lipids, electrocardiographic measures, or prolactin, and no drug-induced movement disorders were observed. Study limitations included limited racial and ethnic diversity, 24-week safety follow-up, a small adult subgroup, and the randomized-withdrawal design, which assessed maintenance of benefit only among initial responders.
Source
Gilbert DL, Atkinson SD, Kim DJB, et al. Efficacy and Safety of Ecopipam for Tourette Syndrome: A Phase 3 Randomized Clinical Trial. JAMA Neurol. 2026;83(7):645–653. doi:10.1001/jamaneurol.2026.1431