Reference: Pediatrics. 2023 Feb 1;151(2):e2022059574; Mov Disord Clin Pract. 2025 Aug;12(8):1157-1166
Practice Point: A novel drug, ecopipam, has a better safety profile than existing medications and may reduce tics in children and adolescents with Tourette syndrome.
EBM Pearl: Although they introduce bias, open-label extensions of randomized trials allow for promising treatments to be received by all study participants and for the analysis of long-term safety and efficacy.
Due to recent unfortunate events at the British Academy of Film and Television Arts (BAFTA) awards and then a subsequent skit on Saturday Night Live, Tourette syndrome (TS) has been making headlines the past few weeks. As a scientist and communicator with TS myself, this seemed like a good time to share some positive news that could impact the TS community and their healthcare providers.
TS is a neurodevelopmental disorder characterized by involuntary motor and vocal tics that begin in childhood and often persist into adulthood. It affects about 1 in 300 individuals < 18 years old, with higher rates in male individuals. Both motor and vocal tics can vary in their frequency, severity, and complexity, causing some individuals to have minimal disruption to their daily functioning while others experience an impactful reduction in their quality of life. Coprolalia (shouting of obscenities) is the most well-known symptom of TS by the public, despite occurring in only 10%-20% of cases. Like many conditions, symptom severity informs management, with treatments that include behavioral, medical, and surgical therapy. While the exact etiology and pathogenesis of TS is unknown, dopamine signaling is likely involved, and thus medical therapy usually targets this system. Indeed, low-dose antipsychotics that block dopamine D2-like receptors are approved for TS treatment in the United States and are recommended when behavioral interventions inadequately control tics. However, many of these medications are associated with adverse effects that often outweigh the benefits they offer.
Ecopipam is the first dopamine D1 receptor antagonist being evaluated as a possible treatment for TS. In a randomized trial of 153 children and adolescents with TS published in 2023, patients receiving ecopipam demonstrated a significant reduction on the Yale Global Tic Severity Score, Total Tic Score (YGTSS-TTS) compared to patients receiving placebo after 12 weeks of treatment (a reduction of 10 points vs. 6.5 points, respectively). Of note, the upper end of the confidence interval for the mean reduction was close to 0 (which would indicate no difference), tempering the otherwise statistically significant results. Nevertheless, the investigators initiated a 12-month open-label extension of the trial to evaluate ecopipam’s long-term safety profile and efficacy. In both the 12-week trial and the 12-month open-label extension, ecopipam did not alter body mass index or blood lipids from baseline over the course of the study. Given that weight gain and dyslipidemia are 2 common reactions to currently available TS medications, these results are exciting!
That said, no medication is a miracle drug, and one-third of the participants did experience some type of treatment-related adverse event, and 1 patient experienced a serious treatment-related adverse event (new-onset obsessive thoughts). Regarding efficacy, the open-label extension analysis reported a YGTSS-TTS reduction of 17.3 points (40% decrease) from baseline at 12 months, a clinically meaningful decrease that is comparable to currently available medications. Although these long-term results lack placebo control, they provide promising data that may indicate a durable treatment response that needs further validation. Importantly, prior ecopipam treatment (or lack thereof) in the initial trial did not influence treatment response in the open-label extension. A stage 3 clinical trial for ecopipam investigating risk of symptom relapse was recently completed, with results awaiting publication.
Unfortunately, successful medical therapy for treating conditions as complex as TS is rare. Thus, while encouraging early data from novel medications is always exciting, it is important to remember that for many neurodevelopmental disorders, including TS, reducing social stigma through public education and awareness can often make the biggest difference in a patient’s life. This has been true of my own experience and is a major goal of TS advocacy groups. Ultimately, the pairing of continued scientific innovation with greater public understanding will be the winning combination that patients with TS are looking for.
For more information, see the topic Tourette Syndrome in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Michael Butler, PhD, Medical Writer at DynaMed. Edited by Katharine DeGeorge, MD, MS, Executive Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Senior Clinical Writer at DynaMed; by Claire Symanski, PhD, Medical Editor and Team Lead for ENT at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.