title: Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome.
abstract: BACKGROUND
  It has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome. In this study, we explored the efficacy of a glutamate agonist (D-serine) and antagonist (riluzole) as tic-suppressing agents in children with Tourette syndrome.
  
  
  METHODS
  We performed a parallel three-arm, 8-week, double-blind, randomized placebo-controlled treatment study in children with Tourette syndrome. Each child received 6 weeks of treatment with D-serine (maximum dose 30 mg/kg/day), riluzole (maximum dose 200 mg/day), or placebo, followed by a 2-week taper. The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score; specifically, the total tic score and the combined score (total tic score + global impairment) between treatment arms after 6 weeks of treatment. Mann-Whitney U tests were performed to analyze differences between each group and the placebo group.
  
  
  RESULTS
  Twenty-four patients (males = 21, ages 9-18) enrolled in the study; one patient dropped out before completion. Combined Yale Global Tic Severity Scale score and total tic scores improved in all groups. The 6-week mean percent improvement of the riluzole (n = 10), D-serine (n = 9), and placebo (n = 5) groups in the combined Yale Global Tic Severity Scale score were 43.7, 39.5, and 30.2 and for total tic scores were 38.0, 25.0, and 34.0, respectively. There were no significant differences in Yale Global Tic Severity Scale score or total tic score, respectively, between the riluzole and placebo (P = 0.35, 0.85) or D-serine and placebo (P = 0.50, 0.69) groups.
  
  
  CONCLUSIONS
  Tics diminished by comparable percentages in the riluzole, D-serine, and placebo groups. These preliminary data suggest that D-serine and riluzole are not effective in tic suppression.
authors.affiliation: Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland. Electronic address: mlemmon2@jhmi.edu.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Lemmon
authors.affiliation: Department of Child Psychiatry, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Marco
authors.initials: M
authors.lastname: Grados
authors.affiliation: Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Tina
authors.initials: T
authors.lastname: Kline
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Carol B
authors.initials: CB
authors.lastname: Thompson
authors.affiliation: Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.affiliation: Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Singer
mesh_terms: D000293:Adolescent; D002648:Child; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D019782:Riluzole / Q000627:therapeutic use*; D012694:Serine / Q000627:therapeutic use*; D012720:Severity of Illness Index; D005879:Tourette Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D012694:Serine; D019782:Riluzole
keywords: Tourette syndrome; d-serine; glutamate; riluzole; tics