1. Alberto J. Espay, MD, MSc,
2. Matthew M. Norris, MEng,
3. James C. Eliassen, PhD,
4. Alok Dwivedi, PhD,
5. Matthew S. Smith, BS,
6. Christi Banks, CCRC,
7. Jane B. Allendorfer, PhD,
8. Anthony E. Lang, MD, FRCPC,
9. David E. Fleck, PhD,
10. Michael J. Linke, PhD and
11. Jerzy P. Szaflarski, MD, PhD

+SHOW AFFILIATIONS

| + SHOW FULL DISCLOSURES

1. Correspondence to Dr. Espay: alberto.espay@uc.edu

1. Published online before print January 28, 2015, doi: 10.1212/WNL.0000000000001282Neurology February 24, 2015 vol. 84 no. 8 794-802

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.