Lack of efficacy of a nicotine transdermal treatment on motor and cognitive deficits in Parkinson's disease

Abstract

Studies assessing the efficacy of nicotine in Parkinson's disease (PD) have generated contradictory results. The controversy seems to stem from uncontrolled factors including the lack of objective measures, the practice effect in a test–retest design, and the absence of plasmatic dosage. This study aimed at further controlling these factors using transdermal nicotine in PD. Methods: Twenty-two nonsmoking PD patients received a transdermal nicotine treatment over 25 days in increasing titrated doses. Motor and cognitive assessments were carried out on days 11 and 25 (low-dose and high-dose assessments, respectively) and after a 14-day washout period. Results: Patients tolerated nicotine poorly. Thirteen (59%) withdrew, mostly because of acute side effects. In the remaining nine patients, nicotine neither improved nor worsened motor or cognitive functioning in comparison with 10 age, gender and education matched controls. Conclusions: Transdermal nicotine is not effective in treating motor and cognitive deficits in PD. The results obtained with our objective measures confirm a recent double-blind, placebo-controlled study that used clinical measures. It is possible that nicotine lacks specificity in targeting critical nicotinic receptors that might be involved in PD pathophysiology. The low tolerability may be related to such a lack of specificity of nicotine, which would directly stimulate the autonomic nervous system.