Abstract

AbstractStemming from the finding that nicotine potentiates haloperidol-induced catalepsy in rats, nicotine in the form of nicotine gum and as transdermal nicotine patch (TNP) has been used in open-label studies to obtund motor and vocal tics of children (age≥8 years, weighi≥25 kg), adolescents, and adults. Reduction of tics was seen during chewing of nicotine gum; the improvement lasted no longer than 1 hour after chewing. With a TNP in subjects who were not responding well to a variety of dopamine blockers, with some also receiving clonidine or a variety of selective serotonin reuptake inhibitors, motor and vocal tics were obtunded 45% over baseline in 85% of 35 subjects within 30 minutes to 3 hours after TNP application. Moreover, the relief of symptoms with a single 7-mg TNP, remaining on the skin for 24 hours, persisted for a variable period of time ranging from 1 to 120 days with an average of 10±2 days. Application of a second TNP for 24 hours when symptoms began to return resulted in a similar reduction in tic severity and frequency, which persisted an average of l3±3 days. Nicotine alone, without D2 blockers, was successful in reducing premonitory urges to tic. After follow-up of 3 to 5 years, 19 of 35 patients continued to use the TNP in gradually decreasing frequency and with gradual reduction in dose of D2 blockers. However, 16 patients (45%), as they grew into middle adolescence, discontinued use of the TNP, stating that they objected to the nausea induced by the patch. There was no evidence of habituation to nicotine. Side effects were not life threatenting; the most disturbing side effect was nausea, appearing 1 to 4 hours after the application of the patch and lasting 1 to 3 hours. There was no change in blood pressure; pulse rate increased from 5 to 10% within 3 hours but returned to baseline after 24 hours. Unsolved problems using TNP are mentioned and a putative mechanism for nicotine effectiveness in Tourette syndrome is briefly discussed.

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