title: Understanding prognostic benefits of exercise and antidepressant therapy for persons with depression and heart disease: the UPBEAT study--rationale, design, and methodological issues.
abstract: BACKGROUND
  Depression is relatively common in patients with coronary heart disease (CHD) and is associated with worse prognosis. Recently there has been interest in evaluating the impact of treating depression on clinical outcomes. Anti-depressant medications have been shown to be safe and efficacious for many patients; exercise also may be effective for treating depression and may also improve cardiopulmonary functioning. However, methodological limitations of previous studies have raised questions about the value of exercise, and no study has compared the effects of exercise with standard anti-depressant medication in depressed cardiac patients.
  
  
  OBJECTIVE
  UPBEAT is a randomized clinical trial (RCT) funded by NHLBI to evaluate the effects of sertraline or exercise compared to placebo on depression and biomarkers of cardiovascular risk in patients with CHD and elevated depressive symptoms.
  
  
  METHODS
  The UPBEAT study includes 200 stable CHD patients with scores on the Beck Depression Inventory (BDI) > or =9 randomized to 4 months of treatment with aerobic exercise, sertraline, or placebo. The primary outcomes include depressive symptoms determined by clinical ratings on the Hamilton Rating Scale for Depression (HAM-D) and measures of heart rate variability (HRV), baroreflex control (BRC), vascular function (i.e., flow-mediated dilation (FMD)), and measures of inflammation and platelet aggregation.
  
  
  RESULTS
  This article reviews the rationale and design of UPBEAT and addresses several key methodologic issues that were carefully considered in the development of this protocol: the use of a placebo control condition in depressed cardiac patients, study design, and selection of intermediate endpoints or biomarkers of cardiovascular risk.
  
  
  CONCLUSIONS
  This study is not powered to assess treatment group differences in CHD morbidity and mortality. Intermediate endpoints are not equivalent to 'hard' clinical events and further studies are needed to determine the clinical significance of these biomarkers.
  
  
  CONCLUSIONS
  The UPBEAT study is designed to assess the efficacy of exercise in treating depression in cardiac patients and evaluates the impact of treating depression on important biomarkers of cardiovascular risk.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. Blume003@mc.duke.edu
authors.forename: James A
authors.initials: JA
authors.lastname: Blumenthal
authors.forename: Andrew
authors.initials: A
authors.lastname: Sherwood
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Rogers
authors.forename: Michael A
authors.initials: MA
authors.lastname: Babyak
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
authors.forename: Lana
authors.initials: L
authors.lastname: Watkins
authors.forename: Benson M
authors.initials: BM
authors.lastname: Hoffman
authors.forename: Cara
authors.initials: C
authors.lastname: O'Connell
authors.forename: Julie J
authors.initials: JJ
authors.lastname: Johnson
authors.forename: Seema M
authors.initials: SM
authors.lastname: Patidar
authors.forename: Robert
authors.initials: R
authors.lastname: Waugh
authors.forename: Alan
authors.initials: A
authors.lastname: Hinderliter
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers; D003863:Depression / Q000188:drug therapy*; D023381:Endpoint Determination; D015444:Exercise / Q000523:psychology*; D005260:Female; D006331:Heart Diseases / Q000523:psychology*; D006801:Humans; D008297:Male; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D020280:Sertraline / Q000627:therapeutic use*; D014481:United States
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D010919:Placebos; D020280:Sertraline