Anti-Inflammatory Action of Antidepressants: Investigating the Longitudinal Effect of Antidepressants on White Blood Cell Count

INTRODUCTION: Antidepressants have documented anti-inflammatory effects on pro-inflammatory biomarkers. However, the long-term effects of antidepressants on inflammatory markers and the effects of different antidepressant classes on pro-inflammatory biomarkers are largely unexplored. Here, we evaluate the short- and long-term effects of all antidepressant classes on a clinical immune marker, white blood cell count (WBC). METHODS: Using a retrospective study design, we extracted WBC count and prescription medications from electronic health records at Vanderbilt University Medical Center. We created a longitudinal model to evaluate the short- and long-term effects of these medications on WBC count. We validated our longitudinal model using two known anti-inflammatory medications, biologic immunosuppressants, and chemotherapy, and one medication class without known immunomodulatory properties, contraceptives. We used the longitudinal model to determine the effects of antidepressant use on WBC count stratified by drug class. RESULTS: Biologic immunosuppressant and chemotherapy use was associated with decreased WBC count, but contraceptive use did not associate with changes in WBC count, validating our longitudinal modeling approach. All antidepressant classes were associated with decreased WBC count in the long-term cohorts. SSRI and atypical use also associated with decreased WBC count in the short-term cohort. CONCLUSIONS: Using electronic health record data, we show all antidepressant classes exhibit anti-inflammatory effects on a clinical immune marker, WBC count. Additionally, our results indicate that in some cases the anti-inflammatory effects of antidepressants persist over at least a 1-year time frame. Our work contributes to the immunomodulatory knowledge of antidepressants and motivates future studies investigating alternative therapeutic routes for antidepressants.