Inflammatory Markers Associated with Antidepressant-Related Side Effects in Patients with Major Depressive Disorder: A Cross-Sectional Study

Background: Major depressive disorder (MDD) has frequently been associated with inflammation; however, the relationship between antidepressant-related side effects and inflammatory markers remains unclear. This study investigated the associations of antidepressant side effects with the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-HDL ratio (MHR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC) count, and C-reactive protein (CRP). Methods: The study included 60 patients aged 18–65 years who met DSM-5 criteria for MDD, had used antidepressants for at least one month, and developed side effects, together with 60 sociodemographically matched healthy controls. Complete blood count (CBC), CRP, and HDL levels were measured from venous blood samples, and NLR, MHR, MLR, and PLR were calculated. Patients completed the Udvalg Kliniske Undersøgelser (UKU) Side Effect Rating Scale, Clinical Global Impression Scale, Montgomery–Åsberg Depression Rating Scale (MADRS), and Hamilton Anxiety Scale (HAM-A). Only side effects considered medication-related according to the UKU causality assessment were included. Analyses were performed using SPSS 24.0. Results: Concentration problems correlated negatively with neutrophil levels and NLR. Sedation/drowsiness correlated positively with MHR and MLR, and increased dreaming correlated positively with platelet levels. Weight gain correlated positively with neutrophil, lymphocyte, and WBC counts and negatively with PLR. Erectile dysfunction correlated negatively with PLR, orgasmic dysfunction with monocyte levels, vaginal dryness with neutrophil levels, and physical dependence with NLR. Conclusions: Antidepressant-related side effects showed several uncorrected associations with peripheral inflammatory markers, none of which survived correction for multiple comparisons (Benjamini–Hochberg false discovery rate). As the first exploratory investigation of this relationship, these preliminary, hypothesis-generating findings may inform understanding of side-effect mechanisms and support future, adequately powered longitudinal studies aimed at enhancing treatment adherence and reducing relapse and chronicity.