title: Clinical trials of add-on medications in Parkinson's disease: Efficacy versus usefulness.
abstract: Clinical trials designed to evaluate the efficacy of new anti-parkinsonian agents often employ an 'add-on' protocol in which patients with motor fluctuations on levodopa are randomized to receive active medication or placebo. Levodopa doses may not be increased, but can be decreased in response to dopaminergic side-effects such as increasing dyskinesia or hallucinations. Although these trials can delineate efficacy, additional studies are necessary to evaluate the usefulness of these medications in the clinical setting. The most important questions to be answered by such studies are: (1) Is the benefit derived from addon medication greater than that which could be brought about by further levodopa titration alone?, and (2) Can 'off' time be decreased and motor function improved without a proportionate increase in unwanted dyskinesia? The short-term symptomatic usefulness of an add-on medication can be evaluated by comparing the effects of the addition of active medication plus levodopa titration to further levodopa titration alone. We discuss the limitations of current add-on protocols as well as protocols which may help address the issue of clinical usefulness.
authors.affiliation: Department of Neurology, University of South Florida College of Medicine, Tampa, Florida, U.S.A.
authors.forename: R A
authors.initials: RA
authors.lastname: Hauser
authors.forename: T A
authors.initials: TA
authors.lastname: Zesiewicz
authors.forename: S A
authors.initials: SA
authors.lastname: Factor
authors.forename: M
authors.initials: M
authors.lastname: Guttman
authors.forename: W J
authors.initials: WJ
authors.lastname: Weiner