title: Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH. alberto.espay@uc.edu.
authors: Alberto J
authors: AJ
authors: Espay
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Matthew M
authors: MM
authors: Norris
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: James C
authors: JC
authors: Eliassen
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Alok
authors: A
authors: Dwivedi
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Matthew S
authors: MS
authors: Smith
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Christi
authors: C
authors: Banks
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Jane B
authors: JB
authors: Allendorfer
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Anthony E
authors: AE
authors: Lang
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: David E
authors: DE
authors: Fleck
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Michael J
authors: MJ
authors: Linke
authors: From the UC Neuroscience Institute, Department of Neurology (A.J.E., C.B., J.P.S.), and Department of Internal Medicine (M.J.L.), University of Cincinnati; Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E.), Cincinnati; University of Cincinnati Center for Imaging Research (M.M.N., J.C.E., M.S.S., D.E.F.), OH; Division of Biostatistics and Epidemiology (A.D.), Texas Tech University Health Sciences Center, El Paso; The Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease (A.E.L.), University Health Network and the University of Toronto, Canada; University of Alabama at Birmingham (J.B.A., J.P.S.); and Department of Veterans Affairs Medical Center (M.J.L.), Research Service, Cincinnati, OH.
authors: Jerzy P
authors: JP
authors: Szaflarski
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000191:economics*; D017281:Cost of Illness; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000191:economics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000008:administration & dosage / Q000191:economics; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000191:economics* / Q000523:psychology; D015990:Placebo Effect; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa
references: Mov Disord. 2008 Apr 15;23(5):690-9
references: 18228568
references: Mov Disord. 2009 May 15;24(7):979-83
references: 19230029
references: Psychosom Med. 2010 Feb;72(2):192-7
references: 20028830
references: Neurosci Biobehav Rev. 2010 Apr;34(5):660-9
references: 19715723
references: J Dev Behav Pediatr. 2010 Jun;31(5):369-75
references: 20495473
references: Nat Med. 2010 Nov;16(11):1277-83
references: 20948533
references: PLoS One. 2010;5(12):e15591
references: 21203519
references: Philos Trans R Soc Lond B Biol Sci. 2011 Jun 27;366(1572):1922-30
references: 21576150
references: Brain Res. 2012 Jun 6;1458:56-66
references: 22560503
references: Mov Disord. 2012 Oct;27(12):1552-5
references: 22362657
references: Psychosom Med. 2013 Jan;75(1):90-6
references: 23115341
references: Brain. 2013 Mar;136(Pt 3):710-25
references: 23423673
references: N Engl J Med. 2001 Mar 8;344(10):710-9
references: 11236774
references: IEEE Trans Med Imaging. 2001 Jun;20(6):535-9
references: 11437113
references: Science. 2001 Aug 10;293(5532):1164-6
references: 11498597
references: Trends Neurosci. 2002 Jun;25(6):302-6
references: 12086748
references: Behav Brain Res. 2002 Nov 15;136(2):359-63
references: 12429397
references: Encephale. 2003 Jan-Feb;29(1):68-71
references: 12640329
references: Arch Gen Psychiatry. 2004 Apr;61(4):412-20
references: 15066900
references: Perception. 2004;33(2):217-36
references: 15109163
references: Neurology. 1967 May;17(5):427-42
references: 6067254
references: Mov Disord. 1992;7(1):2-13
references: 1557062
references: J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
references: 1564476
references: N Engl J Med. 1992 Nov 26;327(22):1549-55
references: 1435881
references: Magn Reson Med. 1995 Sep;34(3):308-12
references: 7500867
references: Comput Biomed Res. 1996 Jun;29(3):162-73
references: 8812068
references: Ann Neurol. 2005 Feb;57(2):298-302
references: 15668979
references: Ann Neurol. 2006 Mar;59(3):459-66
references: 16429411
references: Psychol Sci. 2006 Dec;17(12):1054-8
references: 17201787
references: J Neurosci. 2007 Jul 4;27(27):7105-16
references: 17611263