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 define the clinical domains and demographic groups most affected.


BACKGROUND
Placebo effects are documented in neurology, but the timing and specific disabilities 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 monotherapy ropinerole in PD patients without motor fluctuations. In 105 patients, they evaluated placebo-associated effects on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), dividing the motor examination into four categories: tremor, bradykinesia, rigidity, and gait/balance/midline functions. The motor UPDRS and its subscales were compared over time (at baseline and at 4, 12, and 24 weeks) using Wilcoxon's signed rank test. They applied a rigorous definition of placebo-associated improvement as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by > or =2 points.


RESULTS
During the 6-month study, 16% of subjects improved on placebo treatment. The prevalence of response was steady (8 to 9%) at any one visit without a predominance of an early effect. No patient showed a placebo-associated improvement on all visits. All domains of parkinsonian disability were subject to placebo-associated improvement, with a trend toward more response in bradykinesia and rigidity than in tremor or gait/balance/midline function. Gender, age, disease duration, and baseline disability score did not influence the likelihood of improvement in association with placebo treatment.


CONCLUSIONS
Based on a rigorous definition of placebo-associated improvement, prominent improvements in objective measures of PD disability occur during clinical trials. Because placebo-associated improvements occur throughout a 6-month trial, placebo-controlled studies in PD should be at least 6 months to capture early as well as late improvements.
Goetz
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CG
Department of Neurological Sciences, Rush University, Rush Presbyterian St. Luke's Medical Center, Chicago, IL 60612, USA. mvmtdsrdr@neuro.rush.edu
Leurgans
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Raman
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Stebbins
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GT
D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D010919:Placebos / Q000009:adverse effects / Q000627:therapeutic use*
D010919:Placebos