Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease

The objective of the study was to determine the safety and efficacy of incr easing doses of Rotigotine CDS in patients with advanced Parkinson's diseas e. The development of motor complications in Parkinson's disease has been l inked to intermittent stimulation of dopamine receptors. Continuous, noninv asive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highes t dose (80 cm(2)). Each individual's L-Dopa dose was back-titrated as feasi ble. The primary outcome measure was L-Dopa dose, and secondary outcome mea sures included early morning "off"-L-Dopa Unified Parkinson's Disease Ratin g Scale motor scores by a blinded evaluator and motor fluctuation data obta ined from patient diaries ("on" without dyskinesia, "on" with dyskinesia, a nd "off"). Seven of 10 subjects provided data that could be evaluated. Ther e were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Do pa dose decreased from 1.400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diar y variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data sugg est that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without lo ss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from t he initiation of Parkinson's disease therapy will limit the development of motor complications.