Objective: To examine the effect of cost, a traditionally ?inactive? trait of intervention, as contributor to the response to therapeutic interventions.

Methods: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ? 7.9 years; mean disease duration 11 ? 6 years) who were randomized to a ?cheap? or ?expensive? subcutaneous ?novel injectable dopamine agonist? placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the ?practically defined off? state, before and after each intervention, included the Unified Parkinson’s Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis.

Results: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions.

Conclusion: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies.

Classification of evidence: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.