title: The role of patient expectancy in placebo and nocebo effects in antidepressant trials.
abstract: OBJECTIVE
  To determine whether patient expectancy plays a role in observed placebo and nocebo effects in 2 clinical trials.
  
  
  METHODS
  Data were reanalyzed from 2 fluoxetine-discontinuation studies conducted from March 1990 to September 1992 and from May 1997 to December 2002. The 673 outpatients included were aged 18-65 years with DSM-III-R major depressive disorder (MDD), responded to 12-week duration open treatment, and were randomized to continued fluoxetine or placebo for an additional year. Participants in 1 of the included studies received a fixed dose of fluoxetine 20 mg daily, while the second study utilized flexible fluoxetine doses up to 60 mg daily. Mixed effects longitudinal models determined whether the possible randomization to placebo at 12 weeks resulted in significant depressive symptom worsening across treatments. Correlations were computed between early symptom change (weeks 1-3 of open treatment) and postrandomization symptom change (weeks 13-16 following randomization).
  
  
  RESULTS
  Participants continuing to receive fluoxetine and those switched to placebo had significantly higher mean Hamilton Depression Rating Scale (HDRS) scores immediately postrandomization compared to the final weeks of open treatment (P < .001 for both fluoxetine- and placebo-treated patients). In both studies, early HDRS change was significantly correlated with postrandomization HDRS change for patients receiving fluoxetine (r = -0.46, P < .001) as well as placebo (r = -0.48, P < .001).
  
  
  CONCLUSIONS
  The possibility of receiving placebo following 12 weeks of open fluoxetine was associated with significant symptom worsening in 2 large fluoxetine discontinuation studies. Worsening depression scores following randomization were significantly associated with the degree of improvement participants experienced during weeks 1-3 of open treatment. These results suggest that treatment changes influence patients' expectations of improvement, which, in turn, affect their depressive symptoms.
authors.affiliation: Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, Box 98, New York, NY 10032 brr8@columbia.edu.
authors.forename: Bret R
authors.initials: BR
authors.lastname: Rutherford
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Wall
authors.forename: Andrew
authors.initials: A
authors.lastname: Glass
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Stewart
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064786:Nocebo Effect; D010361:Patients / Q000523:psychology*; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic / Q000523:psychology / Q000592:standards*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D010919:Placebos; D005473:Fluoxetine