Depressive Symptoms, Antidepressant Medication Use, and Inflammatory Markers in the Diabetes Prevention Program

Psychosom Med. Feb/Mar 2018;80(2):167-173. doi: 10.1097/PSY.0000000000000535.


Objective: Antidepressant medication use (ADM) has been shown to predict diabetes. This article assessed the role of inflammatory markers in this relationship within the Diabetes Prevention Program (DPP).

Methods: DPP participants randomized to metformin (MET), life-style intervention (ILS), or placebo (PLB) were assessed for depression (Beck Depression Inventory [BDI]) annually, ADM use semiannually, serum inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6]) at baseline and year 1, and diagnosis of type 2 diabetes mellitus (T2DM) semiannually (for 3.2 years).

Results: At baseline (N = 3187), M (SD) body mass index was 34 (6) kg/m and the median (interquartile range) BDI score was 3 (1-7). One hundred eighty-one (5.7%) reported ADM use and 328 (10%) had BDI scores of 11 or higher. CRP and IL-6 levels did not differ by treatment group. Baseline ADM, but not BDI score, was associated with higher levels of baseline CRP adjusted for demographic, anthropometric variables, and other medications (20% higher, p = .01). Year 1 CRP decreased for non-ADM users in the MET (-13.2%) and ILS (-34%) groups and ADM users in the ILS group (-29%). No associations were found with IL-6. CRP and continuous use of ADM predicted incident T2DM in the PLB group. In the ILS group, continuous and intermittent ADM, but not CRP, predicted T2DM. In the MET group, CRP predicted incident T2DM. CRP did not mediate the risk of T2DM with ADM use in any group.

Conclusions: ADM was significantly associated with elevated CRP and incident T2DM. In the PLB group, ADM and CRP independently predicted onset of T2DM; however, CRP did not significantly mediate the effect of ADM.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Body Mass Index
  • C-Reactive Protein / analysis*
  • Comorbidity
  • Depression* / blood
  • Depression* / drug therapy
  • Depression* / epidemiology
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / prevention & control
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Inflammation* / blood
  • Inflammation* / drug therapy
  • Inflammation* / epidemiology
  • Inflammation* / prevention & control
  • Interleukin-6 / blood*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Outcome Assessment, Health Care / statistics & numerical data*
  • Program Development
  • Risk Reduction Behavior*


  • Antidepressive Agents
  • Hypoglycemic Agents
  • IL6 protein, human
  • Interleukin-6
  • C-Reactive Protein
  • Metformin