title: Placebo improvement in pharmacologic treatment of menopausal hot flashes: time course, duration, and predictors.
abstract: OBJECTIVE
  To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes.
  
  
  METHODS
  Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment group (n = 297). Participants recorded hot flash frequency in diaries twice daily during treatment (Weeks 0-8) and subsequent follow-up (Weeks 9-11). The primary outcome variable was clinically significant improvement, defined as a 50% or greater decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement.
  
  
  RESULTS
  Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at Week 8. Of placebo responders who were improved at both Weeks 4 and 8, 77% remained clinically improved at Week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (odds ratio [OR] = 5.61, 95% confidence interval [CI] = 2.41-13.07, p < .001), current smokers (OR = 2.30, 95% CI = 1.05-5.06, p = .038), and hot flash severity in screening (OR = 1.45, 95% CI = 1.00-2.10, p = .047).
  
  
  CONCLUSIONS
  Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that nonspecific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.
authors: From the Department of Obstetrics/Gynecology and Psychiatry (Freeman), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Epidemiology and Community Health (Ensrud), Department of Medicine, Veterans Affairs Health System, Minneapolis, Minnesota; Department of Medicine (Ensrud), University of Minnesota, Minneapolis, Minnesota; MsFlash Data Coordinating Center (Larson, Guthrie), Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; School of Nursing (Carpenter), Indiana University, Indianapolis, Indiana; Department of Psychiatry (Joffe), Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts; Department of Psychosocial (Joffe) Dana Farber Institute, Harvard Medical School, Boston, Massachusetts; Group Health Research Institute (Newton), Seattle, Washington; Division of Research (Sternfeld), Kaiser Permanente of Northern California, Oakland, California; Women's Health Center, Family and Preventive Medicine (LaCroix), University of California San Diego, La Jolla, California.
authors: Ellen W
authors: EW
authors: Freeman
authors: Kristine E
authors: KE
authors: Ensrud
authors: Joseph C
authors: JC
authors: Larson
authors: Katherine A
authors: KA
authors: Guthrie
authors: Janet S
authors: JS
authors: Carpenter
authors: Hadine
authors: H
authors: Joffe
authors: Katherine M
authors: KM
authors: Newton
authors: Barbara
authors: B
authors: Sternfeld
authors: Andrea Z
authors: AZ
authors: LaCroix
mesh_terms: D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008875:Middle Aged; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015283:Citalopram; D004958:Estradiol; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors
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