USA: Children and adolescents with Tourette syndrome (TS) who take ecopipam experience tics reduction to a greater extent than placebo, says a recent study published in the journal Pediatrics. No evidence of common antipsychotic-associated side effects was observed in children.
All medications approved by the US Food and Drug Administration (USFDA) for Tourette syndrome are antipsychotics. The risk of metabolic changes, weight gain, and drug-induced movement disorders limits their use. Many small trials have suggested that a first-in-class, selective dopamine 1 receptor antagonist (ecopipam) reduces tics with a low risk for these adverse events.

"Treatment decisions for Tourette syndrome require an assessment of disease burden and severity, comorbid conditions, and the concerns of patients and their caregivers regarding the time, cost and side effects of treatments," the researchers wrote.
Against the above background, Donald L. Gilbert from Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, and colleagues sought to further evaluate the safety, efficacy, and tolerability of ecopipam in youth with moderate to severe Tourette syndrome in a randomized, multicenter, double-blind, placebo-controlled, phase 2b trial.
The trial comprised subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20. They were randomly assigned in a ratio of 1:1 to ecopipam (n = 76) or placebo (n = 77). The researchers determined the mean change in the Yale Global Tic Severity Score over 12 weeks (primary endpoint). The secondary endpoint was the Clinical Global Impression of Tourette Syndrome Severity. At each study visit, safety and tolerability were assessed.
The study revealed the following findings:
Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences −3.44).
Improvement in Clinical Global Impression of Tourette Syndrome Severity was also more significant in the ecopipam group.
More weight gain was seen in subjects assigned to placebo.
No metabolic or electrocardiogram changes were identified.
Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events.
Ecopipam showed clinically meaningful improvement in Tourette syndrome based on overall symptom severity and clinician ratings of tics. Tic improvement was also seen in patients with concomitant attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or anxiety disorders at baseline. The researchers did not observe the spectrum of neurologic, psychiatric, metabolic, and cardiac complications associated with D2r antagonists in TS.
"Ecopipam may be a safe and effective treatment of Tourette syndrome with advantages over other approved therapeutic agents,' the researchers concluded.
Reference:
Donald L. Gilbert, Jordan S. Dubow, Timothy M. Cunniff, Stephen P. Wanaski, Sarah D. Atkinson, Atul R. Mahableshwarkar; Ecopipam for Tourette Syndrome: A Randomized Trial. Pediatrics 2023; e2022059574. 10.1542/peds.2022-059574