Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States.
Psychoneuroendocrinology. 2018 Sep;95:43-49. doi: 10.1016/j.psyneuen.2018.05.026. Epub 2018 May 19.
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.
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.
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.
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.
三分之一的重度抑郁症（MDD）患者对现有抗抑郁药物治疗无反应。炎症可能通过影响与抗抑郁疗效相关的神经递质系统而导致治疗无反应。在事后分析中，治疗前炎症标志物浓度的增加预示着抗抑郁反应差。然而，关于目前处于抑郁发作的多次抗抑郁治疗失败的抑郁患者是否表现出炎症增加，数据有限。
测量未接受药物治疗、病情稳定的 MDD 患者（n=98）的血浆炎症标志物浓度，并使用马萨诸塞州综合医院抗抑郁治疗反应问卷测量当前抑郁发作中抗抑郁治疗的充分治疗试验次数。在需要时，在统计模型中包含年龄、性别、种族、教育程度、体重指数（BMI）和抑郁严重程度等协变量。
治疗失败次数与肿瘤坏死因子（TNF）、可溶性 TNF 受体 2（sTNF-R2）和白细胞介素（IL）-6 之间存在显著关系（多元分析中所有 p<0.05）。经过多重检验校正的事后两两比较显示，当前发作中有 3 次或以上治疗失败的患者的血浆 TNF、sTNF-R2 和 IL-6 显著高于仅 0 次或 1 次治疗失败的患者（均 p<0.05）。高敏 C 反应蛋白也与更多的治疗失败次数相关，但仅在排除 BMI 的模型中。
在当前抑郁发作中多次抗抑郁治疗失败的抑郁患者中，测量炎症标志物并靶向炎症或其下游介质可能具有相关性。
