Objective changes in motor function during placebo treatment in PD

Objective: To examine the frequency, temporal development, and stability of objectively derived motor changes during placebo treatment in PD and to de fine the clinical domains and demographic groups most affected. Background: Placebo effects are documented in neurology, but the timing and specific d isabilities most susceptible to changes during placebo treatment in PD have not been examined. Methods: The authors examined the placebo-treated group from a randomized, multicenter, placebo-controlled clinical trial of monot herapy ropinerole in PD patients without motor fluctuations. In 105 patient s, they evaluated placebo-associated effects on the motor section of the Un ified Parkinson's Disease Rating Scale (UPDRS), dividing the motor examinat ion into four categories: tremor, bradykinesia, rigidity, and gait/balance/ midline functions. The motor UPDRS and its subscales were compared over tim e (at baseline and at 4, 12, and 24 weeks) using Wilcoxon's signed rank tes t. They applied a rigorous definition of placebo-associated improvement as an improvement over baseline score in motor UPDRS of at least 50% or a chan ge in at least two motor items at any one visit by greater than or equal to 2 points. Results: During the 6-month study, 16% of subjects improved on p lacebo treatment. The prevalence of response was steady (8 to 9%) at any on e visit without a predominance of an early effect. No patient showed a plac ebo-associated improvement on all visits. All domains of parkinsonian disab ility were subject to placebo-associated improvement, with a trend toward m ore response in bradykinesia and rigidity than in tremor or gait/balance/mi dline function. Gender, age, disease duration, and baseline disability scor e did not influence the likelihood of improvement in association with place bo treatment. Conclusion: Based on a rigorous definition of placebo-associa ted improvement, prominent improvements in objective measures of PD disabil ity occur during clinical trials. Because placebo-associated improvements o ccur throughout a 6-month trial, placebo-controlled studies in PD should be at least 6 months to capture early as well as late improvements.