title: A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome.
abstract: OBJECTIVE
  Dysregulation of dopaminergic signaling has been hypothesized to underlie the motor and phonic tics in Tourette syndrome (TS). The objective of this trial was to evaluate the safety and tic-reducing activity of the selective dopamine D1 receptor antagonist ecopipam in adults with TS.
  
  
  METHODS
  This was a multicenter, nonrandomized, open-label study of 50-mg ecopipam daily (weeks 1-2) and then 100 mg daily (weeks 3-8), taken orally before bedtime. The primary efficacy end point was the change in the Yale Global Tic Severity Scale (YGTSS) total tic score. Comorbid psychiatric symptoms and premonitory urges were rated; weight, serum metabolic studies, and adverse effects were monitored.
  
  
  RESULTS
  Eighteen adults (15 men; 15 white, 2 African American, 1 Asian), with a mean age of 36.2 years (range, 18-63 years), were enrolled, and 15 completed the study. Mean (SD) YGTSS Total Tic score was 30.6 (8.8) at baseline and 25.3 (9.2) at 8 weeks (2-tailed paired t17 = 4.4; P = 0.0004). Mean (SD) YGTSS impairment score was 29.7 (10.9) at baseline and 22.8 (13.7) at final visit (t17 = 2.2; P = 0.04). There was no significant change in premonitory urges or psychiatric symptoms. Mean change in weight was -0.7 kg (P = 0.07). The most commonly reported adverse events were sedation (39%), fatigue (33%), insomnia (33%), somnolence (28%), anxiety (22%), headache (22%), and muscle twitching (22%).
  
  
  CONCLUSIONS
  In this open-label study in adults with TS, tics were reduced after 8 weeks of treatment with ecopipam. To confirm safety and efficacy, randomized, double blind, placebo-controlled trials are warranted.
authors.affiliation: *Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; †Movement Disorders Center, Department of Psychiatry, North Shore-LIJ Health System, Manhasset, NY; Departments of ‡Neurology, §Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD; ∥Atlantic Neuroscience Institute, Overlook Hospital, Summit, NJ; and ¶Psyadon Pharmaceuticals, Inc, Germantown, MD.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gilbert
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Budman
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Singer
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlan
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chipkin
mesh_terms: D000293:Adolescent; D000328:Adult; D001552:Benzazepines / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020323:Tics / Q000188:drug therapy* / Q000209:etiology*; D005879:Tourette Syndrome / Q000150:complications*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; C058081:ecopipam