Long-term Association of Depression Symptoms and Antidepressant Medication Use With Incident Cardiovascular Events in the Look AHEAD (Action for Health in Diabetes) Clinical Trial of Weight Loss in Type 2 Diabetes

Diabetes Care. 2019 May;42(5):910-918. doi: 10.2337/dc18-0575. Epub 2019 Mar 4.


Objective: To examine whether depression symptoms or antidepressant medication (ADM) use predicts the probability of cardiovascular events in overweight/obese individuals with type 2 diabetes.

Research design and methods: Preplanned analyses of depression and incident cardiovascular disease (CVD) were performed in the Look AHEAD (Action for Health in Diabetes) weight loss trial after a median follow-up of 9.6 years. Depression symptoms, assessed with the Beck Depression Inventory (BDI), were analyzed both as a continuous and dichotomized variable (BDI score <10 or ≥10). ADM use was coded from participants' prescription medications. Four composite CVD outcomes were defined in the study protocol. Sex-stratified Cox proportional hazards models were adjusted for a range of baseline covariates.

Results: Depression symptoms were only significantly associated with a composite secondary outcome comprising CVD death, nonfatal myocardial infarction, nonfatal stroke, hospitalized angina, congestive heart failure, peripheral vascular disease, coronary artery bypass graft, and carotid endarterectomy. Significant sex interactions were observed for BDI score and BDI score ≥10. BDI score was significantly associated with higher probability of this composite outcome in men but was not associated with the outcome in women. BDI score ≥10 was positively associated with this composite outcome in men but was negatively associated in women. Exploratory analysis identified a significant BDI ≥10 × ADM use interaction for this composite outcome that differed in men versus women. Men with both BDI score ≥10 and ADM use compared with those with neither had 60% higher probability of the outcome, whereas women with both compared with those with neither had 50% lower probability.

Conclusions: Sex differences in the association of depression symptoms and ADM use with incident CVD warrant further investigation.

Trial registration: ClinicalTrials.gov NCT00017953.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antidepressive Agents / therapeutic use*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology*
  • Cohort Studies
  • Depression / complications
  • Depression / drug therapy*
  • Depression / epidemiology
  • Depressive Disorder / complications
  • Depressive Disorder / drug therapy
  • Depressive Disorder / epidemiology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / psychology
  • Diabetes Mellitus, Type 2 / therapy
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / etiology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / epidemiology*
  • Obesity / therapy*
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Stroke / complications
  • Stroke / epidemiology
  • Stroke / therapy
  • Time Factors
  • Weight Loss / physiology
  • Weight Reduction Programs


  • Antidepressive Agents

Associated data

  • ClinicalTrials.gov/NCT00017953