{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:06:23Z","timestamp":1792008383297,"version":"4.4.0"},"reference-count":18,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Current Tourette syndrome (TS) pharmacotherapy is hindered by adverse effects and high discontinuation rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the safety and maintenance of effect of ecopipam, a selective dopamine D1 receptor antagonist, for up to 24 weeks for TS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This randomized clinical trial was a phase 3, double-blind, placebo-controlled, randomized withdrawal study conducted between January 31, 2023, and February 4, 2025. Participants were enrolled at 77 sites in 12 countries. Individuals 6 years and older with TS were eligible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>In the 12-week, open-label period, ecopipam was titrated over 3 to 4 weeks (target dose, 1.8 mg\/kg per day). Responders (\u226525% improvement in Yale Global Tic Severity Scale Total Tic Score [YGTSS-TTS] at weeks 8 and 12) were randomized to continue ecopipam or taper to placebo for the 12-week double-blind period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Time to relapse (\u226550% loss of open-label period YGTSS-TTS improvement) in participants aged 6 to 18 years (primary) and adults (exploratory).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The trial enrolled 216 participants (n\u2009=\u2009167 [77.3%] pediatric; 146 [67.6%] male and 70 [32.4%] female) to the open-label ecopipam period. Of these, 43 pediatric participants (mean [SD] age, 14.3 [5.5] years) and 8 adult participants were randomized to receive ecopipam; 47 pediatric (mean [SD] age, 14.0 [5.8] years) and 6 adult participants were randomized to receive placebo. Ecopipam significantly reduced the relapse risk vs placebo in pediatric participants (hazard ratio [HR], 0.47; 95% CI, 0.26-0.84;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.008; n\u2009=\u200990). In adults, the effect was directionally similar (HR, 0.51; 95% CI, 0.11-2.30;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.37; n\u2009=\u200914) but not significant. The most frequently reported adverse events with ecopipam (open-label and double-blind periods) were somnolence (n\u2009=\u200924 [11.1%]), anxiety (n\u2009=\u200921 [9.7%]), headache (n\u2009=\u200921 [9.7%]), insomnia (n\u2009=\u200919 [8.8%]), tic (n\u2009=\u200917 [7.9%]), and fatigue (n\u2009=\u200914 [6.5%]). Ecopipam did not have a clinically meaningful impact on weight, metabolic parameters, or psychiatric scale measures. Drug-induced movement disorders were not observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Ecopipam maintained clinically meaningful TS symptom improvements and was well tolerated for up to 24 weeks. Adverse events primarily affected the central nervous system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05615220\">NCT05615220<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.1431","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T15:00:30Z","timestamp":1779807630000},"page":"645","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy and Safety of Ecopipam for Tourette Syndrome"],"prefix":"10.1001","volume":"83","author":[{"given":"Donald L.","family":"Gilbert","sequence":"first","affiliation":[{"name":"Division of Neurology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah D.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Emalex Biosciences Inc, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J. 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