title: Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder.
abstract: OBJECTIVE
  The safety and efficacy of mecamylamine as a monotherapy in children and adolescents with Tourette's disorder (TD) was investigated in an 8-week multicenter, double-blind, placebo-controlled study.
  
  
  METHODS
  Eligible subjects included subjects with TD (DSM-IV), with a naturalistic mix of comorbid diagnoses, nonsmokers, aged 8 to 17 years, whose behavioral and emotional symptoms (according to parents) were more disturbing than tics. After a washout period of all psychotropic medication, subjects were randomly assigned to either mecamylamine (n = 29) or placebo (n = 32). Mecamylamine doses ranged from 2.5 to 7.5 mg/day. Primary efficacy measures included the Tourette's Disorder Scale-Clinician Rated (TODS-CR) and 21-point Clinical Global Improvement scale; secondary efficacy measures included the Yale Global Tic Severity Scale and a rage-attack scale (RAScal).
  
  
  RESULTS
  Of the 61 subjects who were randomized, 50 (82%) completed at least 3 weeks on medication and 38 (62%) completed the full 8-week trial. Study withdrawals included 12/29 on mecamylamine and 11/32 on placebo. For the total sample, mecamylamine was no more effective than placebo on any of the outcome measures. However, an item analysis of the TODS-CR suggested that mecamylamine may have reduced sudden mood changes and depression in moderately to severely affected subjects. Except for a slight increase in heart rate during the 1st week in both the mecamylamine and the placebo groups, there where no significant mecamylamine-related changes in vital signs, electrocardiogram, complete blood cell count, or blood chemistry values.
  
  
  CONCLUSIONS
  Mecamylamine, in doses up to 7.5 mg/day, is well tolerated in children and adolescents, but as a monotherapy it does not appear to be an effective treatment for tics or for the total spectrum of symptoms associated with TD. However, further studies should be conducted to investigate its possible therapeutic effects in subjects with comorbid mood disorders and as an adjunct to neuroleptic medication.
authors.affiliation: University of South Florida College of Medicine, Tampa 33613, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Silver
authors.forename: R D
authors.initials: RD
authors.lastname: Shytle
authors.forename: K H
authors.initials: KH
authors.lastname: Sheehan
authors.forename: D V
authors.initials: DV
authors.lastname: Sheehan
authors.forename: A
authors.initials: A
authors.lastname: Ramos
authors.forename: P R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000293:Adolescent; D002648:Child; D015897:Comorbidity; D003863:Depression; D004311:Double-Blind Method; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D019964:Mood Disorders; D010919:Placebos; D012720:Severity of Illness Index; D005879:Tourette Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D005730:Ganglionic Blockers; D010919:Placebos; D008464:Mecamylamine