Ecopipam Tourette
(2026)Objective
To evaluate the safety and maintenance of effect of ecopipam, a selective dopamine D1 receptor antagonist, for up to 24 weeks in children, adolescents, and adults with Tourette syndrome.
Study Summary
• In adults, effect was directionally similar but not significant (HR 0.51; 95% CI 0.11-2.30; P=.37; n=14)
• Mean YGTSS-TTS reduction at week 12 was -47.5% in pediatric and -38.9% in adult populations
• Most common AEs: somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), tic (7.9%), fatigue (6.5%)
• No clinically meaningful impact on weight, metabolic parameters, or psychiatric scale measures; no drug-induced movement disorders observed
Intervention
Ecopipam 1.8 mg/kg per day (administered as ecopipam hydrochloride 2 mg/kg per day) orally vs placebo, following a 12-week open-label ecopipam lead-in with randomization of responders to a 12-week double-blind withdrawal period.
Inclusion Criteria
Age ≥6 years, weight ≥18 kg, Tourette syndrome diagnosis by DSM-5-TR criteria, motor and vocal tics causing impairment with normal routines, YGTSS-TTS ≥20 at screening and baseline.
Study Design
Arms: Ecopipam 1.8 mg/kg/day (n=51; 43 pediatric, 8 adult) vs Placebo (n=53; 47 pediatric, 6 adult)
Patients per Arm: Ecopipam n=51, Placebo n=53
Outcome
• Adult relapse: directionally similar but not significant (HR 0.51; 95% CI 0.11-2.30; P=.37)
• Ecopipam well tolerated; AEs primarily CNS-related (somnolence, anxiety, headache, insomnia, fatigue)
• No clinically meaningful changes in weight, metabolic, or psychiatric measures
• No drug-induced movement disorders observed
Bottom Line
Ecopipam 1.8 mg/kg/day significantly reduced the risk of relapse and maintained clinically meaningful tic reduction over 24 weeks in pediatric patients with Tourette syndrome, with adverse events primarily affecting the central nervous system and no clinically meaningful effects on weight, metabolic parameters, or drug-induced movement disorders.
Major Points
- Phase 3 randomized withdrawal design: 12-week open-label ecopipam lead-in, then responders (≥25% YGTSS-TTS improvement) randomized 1:1 to continue ecopipam or taper to placebo for 12 weeks.
- In pediatric participants (n=90), ecopipam significantly reduced relapse risk vs placebo (HR 0.47; 95% CI 0.26-0.84; P=.008).
- In adults (n=14), effect was directionally similar but underpowered and not significant (HR 0.51; 95% CI 0.11-2.30; P=.37).
- Open-label YGTSS-TTS reduction at week 12 was -47.5% (pediatric) and -38.9% (adults).
- Most common AEs were CNS-related: somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), tic (7.9%), fatigue (6.5%).
- No clinically meaningful changes in weight, metabolic parameters, or psychiatric scales; no drug-induced movement disorders observed.
- Provides evidence for a novel mechanism (selective D1 receptor antagonism) for sustained TS symptom control without typical D2-related metabolic and movement adverse effects.
Study Design
- Study Type
- Phase 3 randomized, double-blind, placebo-controlled, randomized withdrawal trial
- Randomization
- Yes
- Blinding
- Double-blind (participants, caregivers, investigators, study staff masked) during 12-week double-blind withdrawal period; preceded by 12-week open-label ecopipam period
- Sample Size
- 216
- Follow-up
- Up to 24 weeks (12-week open-label + 12-week double-blind withdrawal)
- Centers
- 77
- Countries
- United States, Bulgaria, Canada, Denmark, France, Germany, Hungary, Italy, Poland, Romania, Serbia, Spain
Primary Outcome
Definition: Time from randomization to relapse in pediatric participants (aged 6-18 years); relapse defined as ≥50% loss of YGTSS-TTS improvement from baseline to week 12, initiation of additional medications for TS, or hospitalization due to worsening TS
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Placebo, pediatric n=47 (36 relapsed) | Ecopipam, pediatric n=43 (21 relapsed) | 0.47 (0.26-0.84) | 0.008 |
Limitations & Criticisms
- Small adult subgroup (n=14 randomized) limits ability to detect effect in adults
- Randomized withdrawal design enriches for responders, which may inflate apparent treatment effect compared to a parallel-group design
- Open-label lead-in introduces selection bias by excluding non-responders before randomization
- Short double-blind follow-up (12 weeks) limits assessment of longer-term durability
- Industry-sponsored trial (Emalex Biosciences / Paragon Biosciences authorship)
Citation
JAMA Neurol. doi:10.1001/jamaneurol.2026.1431. Published online May 26, 2026.