The selective dopamine D1 receptor antagonist ecopipam maintains tic suppression for up to 24 weeks and lowers the risk of relapse by 50 percent in children with Tourette syndrome, as shown in a phase III trial.
At week 24, the primary outcome of relapse—defined as a ≥50-percent loss of open-label period YGTSS-TTS* improvement—in participants aged 6–18 years had occurred in 41.9 percent in the ecopipam arm vs 68.1 percent in the placebo arm (hazard ratio [HR], 0.47, 95 percent confidence interval [CI], 0.26–0.84; p=0.008). [JAMA Neurol 2026;doi:10.1001/jamaneurol.2026.1431]
“Median time from randomization (week 12) to relapse was 4 weeks for placebo and was not estimable for ecopipam, because more than 50 percent of participants maintained improvement at week 24,” the investigators reported.
The beneficial effect of ecopipam on relapse risk was consistent in the combined paediatric and adult population (41.2 percent vs 67.9 percent; HR, 0.47, 95 percent CI, 0.28–0.81; p=0.005).
An exploratory analysis limited to adult participants showed a trend toward a lower relapse risk with ecopipam vs placebo (66.7 percent vs 37.5 percent; HR, 0.51, 95 percent CI, 0.11–2.30; p=0.37).
Well-tolerated
As for safety, “adverse events (AEs) were predominantly associated with the central nervous system, as in previous trials, with the most frequently reported AEs during ecopipam treatment being somnolence (11.1 percent), anxiety (9.7 percent), headache (9.7 percent), insomnia (8.8 percent), tic (7.9 percent), and fatigue (6.5 percent),” the investigators noted. [Pediatrics 2023;151:e2022059574; Mov Disord Clin Pract 2025;12:1157-1166]
Serious AEs were reported in four participants overall, including two events considered possibly or probably related to ecopipam. One was an episode of mild acute kidney injury and moderately elevated blood creatine phosphokinase concomitant with dehydration, and another was suicidal ideation.
AEs led to treatment discontinuation in 15.7 percent of ecopipam-treated participants.
“In this trial, ecopipam treatment for up to 24 weeks was not associated with clinically meaningful changes in body mass index z-scores, glycated haemoglobin, lipids, ECG measurements, or prolactin and did not cause drug-induced movement disorders. Additionally, [the drug] had no negative impact on scale measures for ADHD, anxiety, depression, and obsessive-compulsive disorder,” they added.
These safety data have important clinical implications, given that the use of antipsychotics—currently the only approved medications for Tourette syndrome—is limited by the associated risk of weight gain, adverse metabolic changes, and drug-induced movement disorders, the investigators pointed out. [Lancet Child Adolesc Health 2023;7:112-126]
Novel option
“Based on its tolerability profile, efficacy, mechanism of action, and current phase 3 and previous phase 2b positive results, ecopipam could be a novel pharmacologic treatment option for children, adolescents, and adults with Tourette syndrome,” they concluded. [Pediatrics 2023;151:e2022059574]
The phase III trial consisted of a 12-week open-label and a 12-week double-blind treatment periods. In the 12-week, open-label period, 216 participants (167 children and 49 adults, 67.6 percent male) received ecopipam, which was titrated over 3 to 4 weeks for a target dose of 1.8 mg/kg per day. Those who responded to treatment (≥25-percent improvement in YGTSS-TTS at weeks 8 and 12; 90 children and 14 adults) were randomized to continue ecopipam (n=51) or taper to placebo (n=53) for the 12-week double-blind treatment period.
During the open-label period, YGTSS-TTS decreased by 47.5 percent in children and by 38.9 percent in adults among those who completed the 12-week treatment. A total of 73.2 percent of participants achieved a ≥25-percent improvement, 34.7 percent achieved a ≥50-percent improvement, 4.7 percent achieved a ≥75-percent improvement, and 1.4 percent achieved a 100-percent improvement in YGTSS-TTS at one or more study visits.
The investigators acknowledged several study limitations, including minimal racial and ethnic diversity, safety assessment being limited to 24 weeks, low statistical power for the adult subgroup, open-label responder assessment being based on predefined operational criteria, and the small number of adults included, among others.