Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. (September 2018)

• Record Type: Journal Article
• Authors: Haroon, Ebrahim; Daguanno, Alexander W.; Woolwine, Bobbi J.; Goldsmith, David R.; Baer, Wendy M.; Wommack, Evanthia C.; Felger, Jennifer C.; Miller, Andrew H.
• Is Part Of: Psychoneuroendocrinology. Volume 95(2018)
• Page Start: 43
• Page End: 49
• Publication Date: 2018-09
• Subjects: Cytokines -- C-reactive protein -- Interleukin-6 -- Tumor necrosis factor -- Treatment resistant depression; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2018.05.026
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: Antidepressant treatment trials were measured in the current episode of depression. Patients with multiple failed treatment trials had increased inflammatory markers. TNF, sTNF-R2, IL-6 and CRP were associated with number of failed treatment trials. Treatment non-response can be associated with increased inflammation. Abstract: Background: One third of patients with major depressive disorder (MDD) fail to respond to currently available antidepressant medications. Inflammation may contribute to treatment non-response through effects on neurotransmitter systems relevant to antidepressant efficacy. In post-hoc analyses, increased concentrations of inflammatory markers prior to treatment predict poor antidepressant response. However, limited data exists on whether depressed patients with multiple failed treatment trials in their current episode of depression exhibit increased inflammation. Methods: Plasma concentrations of inflammatory markers were measured in unmedicated, medically stable patients with MDD (n = 98) and varying numbers of adequate antidepressant treatment trials in the current depressive episode as measured by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire. Covariates including age, sex, race, education, body mass index (BMI) and severity of depression were included in statistical models where indicated. Results: A significant relationship was found between number of failed treatment trials and tumor necrosis factor (TNF), soluble TNF receptor 2 (sTNF-R2) and interleukin (IL)-6 (all p < 0.05 in multivariate analyses). Post hoc pairwise comparisons with correction for multiple testing revealed that patients with 3 or more failed trials in the current episode had significantly higher plasma TNF, sTNF-R2 and IL-6 compared to individuals with 0 or 1 trial (all p < 0.05). High sensitivity c-reactive protein was also associated with a greater number of treatment failures, but only in models with BMI excluded. Conclusions: Measuring inflammatory markers and targeting inflammation or its downstream mediators may be relevant for depressed patients with multiple failed antidepressant treatment trials in their current depressive episode.