Ecopipam cut relapse risk in children with Tourette syndrome in a phase 3 trial

Children and adolescents with Tourette syndrome who responded to ecopipam and then kept taking it were roughly half as likely to relapse as those tapered onto placebo, in a phase 3 randomised-withdrawal trial published in JAMA Neurology [s1]. The result matters because every medication the US Food and Drug Administration has approved for Tourette syndrome is an antipsychotic, a class whose use is limited by weight gain, metabolic change and drug-induced movement disorders [s2].

Ecopipam is a first-in-class, selective dopamine D1 receptor antagonist — a different mechanism from the D2-blocking antipsychotics that dominate current treatment [s2]. The trial was sponsored by Emalex Biosciences, the company developing the drug, a funding arrangement worth keeping in view when weighing a favourable result [s3].

How the trial was built

The study enrolled 216 people aged 6 years or older with Tourette syndrome at 77 sites in 12 countries, running between 31 January 2023 and 4 February 2025 [s1]. It used a randomised-withdrawal design: every participant first received open-label ecopipam for 12 weeks, titrated over three to four weeks to a target dose of 1.8 mg/kg per day [s1]. Those who responded — a 25% or greater improvement in the Yale Global Tic Severity Scale Total Tic Score at weeks 8 and 12 — were then randomly assigned either to continue ecopipam or to taper onto placebo for a 12-week double-blind period [s1].

The primary outcome was time to relapse, defined as losing at least half of the tic improvement gained during the open-label phase, in participants aged 6 to 18; the same outcome in adults was exploratory [s1]. Of the 216 who entered the open-label phase, 167 (77.3%) were children or adolescents; 146 (67.6%) were male and 70 (32.4%) female [s1]. In the randomised phase, 43 paediatric participants and 8 adults continued ecopipam, while 47 paediatric participants and 6 adults tapered to placebo [s1].

What the numbers showed

Among the 90 children and adolescents randomised, continuing ecopipam cut the risk of relapse by more than half compared with switching to placebo: a hazard ratio of 0.47 (95% confidence interval, 0.26 to 0.84; P=.008) [s1]. In the 14 adults, the direction was similar but the estimate was too imprecise to interpret — a hazard ratio of 0.51 with a confidence interval running from 0.11 to 2.30 (P=.37) [s1]. That adult result reflects how few adults the trial randomised, not evidence that the drug fails in them.

The safety profile was the selling point. The most common adverse events on ecopipam were somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), tics (7.9%) and fatigue (6.5%) [s1]. Crucially for a drug meant to sidestep the liabilities of antipsychotics, ecopipam had no clinically meaningful effect on weight, metabolic measures or psychiatric scales, and no drug-induced movement disorders were observed [s1].

It builds on an earlier trial

This is not ecopipam's first controlled test. A phase 2b trial published in Pediatrics in 2023 randomised 153 children and adolescents with moderate-to-severe Tourette syndrome — 76 to ecopipam, 77 to placebo — and found tic scores fell further on the drug over 12 weeks, a least-squares mean difference of −3.44 points on the same tic scale (95% confidence interval, −6.09 to −0.79; P=.01) [s2]. That trial, too, reported more weight gain in the placebo group than on ecopipam, the mirror image of what antipsychotics tend to do [s2].

The phase 3 trial adds a different kind of evidence. Rather than asking whether ecopipam beats placebo from the start, its withdrawal design asks whether the benefit persists — whether responders who stay on the drug hold their gains better than those taken off it. The answer, in children, was yes [s1].

What it does and does not settle

The caveats are real. The primary result rests on 90 randomised children, and the adult arm was too small to interpret [s1]. A randomised-withdrawal design enriches the sample for people who have already responded to and tolerated the drug, so it speaks to maintenance of effect, not to how an unselected patient will fare starting treatment. And the trial was funded by the drug's manufacturer, the arrangement that most often accompanies favourable industry results [s3]. Independent replication and longer follow-up would strengthen the case.

Even so, for a condition whose approved drugs are all antipsychotics, an agent that maintained tic control over 24 weeks without weight gain, metabolic disturbance or new movement disorders is a genuinely different option — if regulators agree the evidence is sufficient [s1][s2]. This article describes trial findings and is not medical advice.

Sources

• Efficacy and Safety of Ecopipam for Tourette Syndrome — JAMA Neurology, 2026-07-01
• Ecopipam for Tourette Syndrome: A Randomized Trial — Pediatrics, 2023-01-11
• Ecopipam trial registration (NCT05615220) — ClinicalTrials.gov