Following reports that either systemic or intracaudate administration of nicotine potenti¬ates the cataleptic properties of haloperidol (Haldol) in rats, open-trial clinical studies utilizing nicotine gum and transdermal nicotine patch suggest that nicotine potentiates the action of neuroleptics in relieving the motor and vocal tics of Tourette Syndrome (TS). This strategy of co-therapy may offer a significant improvement in the treatment of TS over currently available therapies. The advantage to using nicotine as an adjunct to neuroleptics is the possibility of reducing neuroleptic dosage. This investigation will study the safety and efficacy of trans¬dermal nicotine as an adjunct to haloperidol in TS treatment. Seventy subjects, ages 8 to 18, who are being treated with an individually-based optimum dose of haloperidol will be recruited for this double-blind placebo-controlled multi-site study. The primary outcome measures will be assessed by the Yale Global Tic Severity Scale, Global Improvement Scales, Conner’s Parent Rating Scale, Gordan Diagnostic System, and video tape assessments (for tic frequency and severity). Following a baseline evaluation, subjects will receive, in a predetermined randomized fashion, either transdermal nicotine (7 mg/24 hrs) or placebo patches, such that 35 subjects will receive nicotine and 35 subjects will receive placebo. Each subject will wear a new patch each day for 5 days while concurrently taking their optimum daily dose of haloperidol, then 14 days of wearing a new patch each day plus ••• the starting dose of haloperidol, and finally an additional 14 days without the patch plus ••• the starting dose of haloperidol. In summary, the results of this project will determine if cholin¬ergic nicotine receptor modulation is a useful pharmacological strategy for the augmentation of the treatment of individuals diag¬nosed with Tourette Syndrome. Paul R. Sanberg, Ph.D. University of South Florida College of Medicine, Tampa, FL Brian J. McConville, M.D., Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH Award $24,300 SHELDON NOVICK, M.D. MEMORIAL AWARD Tourette Association of America Inc. – Research Grant Award 1996