Antidepressant Effects on Insulin Sensitivity and Proinflammatory Cytokines in the Depressed Males

Abstract

Growing evidence suggests that mood disorder is associated with insulin resistance and inflammation. Thus the effects of antidepressants on insulin sensitivity and proinflammatory responses will be a crucial issue for depression treatment. In this study, we enrolled 43 non-diabetic young depressed males and adapted standard testing procedures to assess glucose metabolism during 4-week hospitalization. Before and after the 4-week antidepressant treatment, participants underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity (SI), glucose effectiveness (SG), acute insulin response, and disposition index (DI) were estimated using the minimal model method. The plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and adiponectin were measured. The Hamilton depression rating scale (HAM-D) total scores were reduced significantly during the course of treatment. There were no significant changes in the parameters of SI, SG, and DI. Compared to drug naïve status, the level of plasma IL-6 was significantly elevated (0.77 to 1.30 pg/ml; P = .001) after antidepressant therapy. However, the concentrations of CRP, TNF-α, and adiponectin showed no differences during the course of treatment. The results suggest that antidepressants may promote stimulatory effect on the IL-6 production in the early stage of antidepressant treatment.

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

“…In order to explore whether fluoxetine effects on inflammation depend on the quality of the living environment, we analyzed hippocampal expression levels of seven immune mediators reportedly involved in antidepressant drug action (Carvalho et al, 2013;Chen et al, 2010;Eller et al, 2008;Hannestad et al, 2011;Kim et al, 2013;Lanquillon et al, 2000;Song et al, 2009;Tuglu et al, 2003) and affected by environmental stimuli (Chabry et al, 2015;Goshen et al, 2008;Singhal et al, 2014;Wohleb et al, 2011). In particular, we focused on IL-6, TNFα and IL-1β, which are pro-inflammatory cytokines among the most studied in relation to antidepressant effects (Carvalho et al, 2013;Eller et al, 2008;Hannestad et al, 2011).…”

“…However, other clinical studies obtained opposite results, demonstrating no or even pro-inflammatory effects of antidepressant treatment (Chen et al, 2010;Haastrup et al, 2012;Hannestad et al, 2011;Jazayeri et al, 2010;Kim et al, 2013;Song et al, 2009). Experimental studies reflect the incongruence of clinical findings.…”

“…Indeed, though many studies showed that antidepressants have anti-inflammatory effects (Basterzi et al, 2005;Kagaya et al, 2001;Lanquillon et al, 2000;Leo et al, 2006;Tuglu et al, 2003;Yoshimura et al, 2009), an increasing number of studies are reporting a proinflammatory action (Chen et al, 2010;Haastrup et al, 2012;Hannestad et al, 2011;Jazayeri et al, 2010;Kim et al, 2013;Song et al, 2009). In addition, the bi-directional crosstalk between SSRI administration and inflammation has been described also by studies investigating the effects of antiinflammatory drugs on antidepressant efficacy.…”

A Review of the Association Between Depression and Insulin Resistance: Pitfalls of Secondary Analyses or a Promising New Approach to Prevention of Type 2 Diabetes?

“…Insulin sensitivity increased only in the patients who remitted from major depressive disorder as a result of either antidepressant treatment, even after correcting for body mass index. In a Taiwanese 4-arm, randomized controlled trial comparing 4 types of antidepressants (maprotiline, fluoxetine, venlafaxine, and mirtazapine) in 43 men with DSM-IV depression based on clinical interview, there was no change in insulin sensitivity following treatment with any of the antidepressants [24]. It is difficult to interpret either of these randomized controlled trials, as there was no depressed control group that received no treatment.…”

Do Antidepressants Exert Effects on the Immune System?

“…In the study by Chen et al ( 2010 ) 43 young depressed males were treated with one of four antidepressants as inpatients for 4 weeks. Among other parameters, hsCRP, TNF-α, and IL-6 were measured before and after treatment.…”