Effect of Metabolic Syndrome on Late‐Life Depression: Associations with Disease Severity and Treatment Resistance

Background/Objectives Metabolic syndrome (MetS) is the co‐occurrence of obesity and metabolic derangements. Prior research implicates MetS in prolongation of the course of depression in older adults, but its effect on antidepressant response is unknown in this population. The objective was to determine whether MetS and related metabolic dyscrasias are associated with decreased rate of remission from depression in older adults treated pharmacologically for depression. Design Secondary analysis of a randomized controlled trial. Setting Three academic medical centers in North America. Participants Adults aged 60 and older (mean age 69.1) with major depressive disorder (MDD) (N = 435). Intervention Open‐label, protocolized treatment with extended‐release venlafaxine for 12 or more weeks. Measurements Time to remission from depression, with remission defined as a Montgomery‐Åsberg Depression Rating Scale (MADRS) score of 10 or less at last two visits. Results Two hundred twenty‐two participants (51%) met criteria for MetS at baseline; MetS was associated with greater severity (MADRS score) and chronicity of depression at baseline. Remission was achieved in 182 participants (42%). In the unadjusted analysis, MetS was associated with prolonged time to remission (hazard ratio for remission = 0.71, 95% confidence interval = 0.52–0.95), but this relationship was not significant in the adjusted model; greater number of MetS components and lower high‐density lipoprotein cholesterol had similar effects. Only diastolic blood pressure (DBP) was a significant predictor of time to remission before and after adjustment, with higher DBP predicting longer time to remission. Insulin sensitivity did not predict time to remission. Conclusion The presence of MetS in older adults with depression was associated with greater symptom severity and chronicity of depression, which appears to have accounted for the poorer antidepressant response observed in those with MetS. Additionally, our preliminary finding of an association between higher DBP and poorer antidepressant response bears further examination and replication.