Ecopipam Maintains Tic Suppression In Tourette Syndrome Trial
Key Takeaways
- Relapse during withdrawal was less frequent with continued ecopipam in pediatric participants and showed a similar pattern in the overall randomized population.
- Exploratory tic and global impression measures generally favored continued ecopipam, while the small adult analysis was directionally similar without statistical significance.
- Adverse events were mainly CNS-related.
The phase 3 randomized withdrawal trial in JAMA Neurology used a double-blind, placebo-controlled design after a 12-week open-label response period, with up to 24 weeks of exposure. Rather than testing de novo treatment response, the randomized comparison examined maintenance after initial improvement.
The multicenter study was conducted at 77 sites in 12 countries from January 31, 2023, through February 4, 2025 in participants aged 6 years and older. All participants entered a 12-week open-label ecopipam period, with titration over 3 to 4 weeks to 1.8 mg/kg per day. Responders, defined by at least 25% YGTSS-TTS improvement at both weeks 8 and 12, were randomized 1:1 to continue ecopipam or taper to placebo for 12 weeks. The study enrolled 216 participants, including 167 pediatric and 49 adult participants, and randomized 104 responders after 12 weeks.
In pediatric participants, ecopipam reduced relapse risk versus placebo, with HR 0.47 (95% CI, 0.26-0.84; P = .008). The overall randomized population showed the same hazard ratio, HR 0.47 (95% CI, 0.28-0.81; P = .005). Among pediatric participants, relapse occurred in 68.1% of placebo-treated participants and 41.9% of ecopipam-treated participants, and median time to relapse was 4.0 weeks for placebo. Median time to relapse with ecopipam was not estimable because more than half maintained improvement through week 24. In adults, the exploratory analysis also favored ecopipam, but the finding was not significant, with HR 0.51 (95% CI, 0.11-2.30; P = .37).
An exploratory analysis of YGTSS-TTS change from randomization to end of treatment also favored ecopipam, with a least-squares mean difference of -5.1 (95% CI, -8.8 to -1.4; P = .009). Motor and phonic tic subscales, YGTSS-I, YGTSS-GS, CGI-TS-S, CGI-TS-I, and CaGI-C moved in the same direction. During open-label treatment, 156 of 216 participants showed at least 25% improvement at one or more visits, reflecting the responder-enriched randomized phase.
The authors noted limited racial and ethnic diversity, low statistical power for adults, safety assessment limited to 24 weeks, and responder-only randomization, which constrained generalizability and supported a maintenance-of-effect reading.
Across ecopipam exposure, the most frequent adverse events were somnolence in 24 participants, anxiety or headache in 21, insomnia in 19, tic in 17, and fatigue in 14. Treatment discontinuation because of adverse events occurred in 34 participants, or 15.7%, and serious adverse events occurred in 4 participants, with 2 considered possibly or probably related. Investigators reported no clinically meaningful effects on weight, metabolic parameters, or psychiatric scale measures, and no drug-induced movement disorders were observed. No suicidal behavior occurred, although one suicidal ideation event arose during placebo exposure after ecopipam taper.
The authors concluded that ecopipam maintained clinically meaningful tic-suppression efficacy for up to 24 weeks and was well tolerated.