title: Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study.
abstract: BACKGROUND
  Preclinical animal and open-trial clinical trials using nicotine gum and the transdermal nicotine patch found that treatment with nicotine potentiates the effects of neuroleptics in reducing the dyskinetic symptoms of Tourette's disorder. We sought to verify and expand these findings in a prospective double-blind placebo-controlled trial.
  
  
  METHODS
  Seventy patients with DSM-IV Tourette's disorder were treated with either transdermal nicotine (7 mg/24 hours) or placebo patches in a 33-day, randomized, double-blind study. Each patient received an individually based optimal dose of haloperidol for at least 2 weeks prior to random assignment to nicotine or placebo treatment. A new patch was worn each day for the first 5 days. On the sixth day, the dose of haloperidol was reduced by 50%. Daily patch applications were then continued for an additional 2 weeks (through day 19), at which time the patch was discontinued, but the 50% dose of haloperidol was continued for an additional 2 weeks (through day 33). Clinical and safety assessments were made at each visit.
  
  
  RESULTS
  Patients who completed all 19 days of nicotine (N = 27) or placebo (N = 29) patch treatment were used in efficacy analyses. As documented by the Clinician- and Parent-rated Global Improvement scales, transdermal nicotine was superior to placebo in reducing the symptoms of Tourette's disorder. The Yale Global Tic Severity Scale was less sensitive in detecting a placebo/drug difference than were the global improvement scores, suggesting that some of the improvement may not have been related to treatment-related changes in tic severity, but to the emotional and behavioral symptoms. The side effects of nausea and vomiting were significantly more common in the nicotine group (71% [N = 25] and 40% [N = 14]) than in the placebo group (17% [N = 6] and 9% [N = 3]) (nausea, p = .0001; vomiting, p = .004).
  
  
  CONCLUSIONS
  Transdermal nicotine was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol, when the dose of haloperidol was reduced by 50%, and when the patch had been discontinued for 2 weeks. These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette's disorder. While side effects limit chronic use of nicotine, it may be useful on a p.r.n. basis. Further clinical research is warranted to investigate the use of novel nicotinic receptor modulating agents with improved safety profiles over nicotine.
authors.affiliation: Center for Infant and Child Development, Department of Psychiatry and Behavioral Medicine, 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: M K
authors.initials: MK
authors.lastname: Philipp
authors.forename: B J
authors.initials: BJ
authors.lastname: Wilkinson
authors.forename: B
authors.initials: B
authors.lastname: McConville
authors.forename: P R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000279:Administration, Cutaneous; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003367:Cotinine / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009538:Nicotine / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D005879:Tourette Syndrome / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D009538:Nicotine; D006220:Haloperidol; D003367:Cotinine