Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression

Abstract

Background: This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression. Methods: Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels. Results: HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p < 0.05) reduced to 13.47 ± 1.77 at 12 weeks of treatment. In responders, mean serum BDNF levels at the start of treatment were 2.32 ± 0.3 ng/ml, which significantly (p < 0.05) increased to 2.79 ± 0.33 ng/ml at 12 weeks of treatment and mean serum TNF-α levels at the start were 5.18 ± 0.67 pg/ml, which significantly decreased to 4.36 ± 0.72 pg/ml (p < 0.05) at 12 weeks of treatment. Conclusion: Our results suggest that mirtazapine is effective and well tolerated in severely depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels.

Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis

“…In consequence of MDD-related stress it influences the vagal afferent pathways associated with hypothalamus-pituitary-adrenal axis promoting inflammatory processes in CNS. Numerous studies showed TNF-α decrease post antidepressant treatment, although it is inconsistent with our results [Gupta et al, 2016;Halaris at al., 2015;Li et al, 2013].…”

“…Some researchers proved that decreases of pro-inflammatory cytokines were more pronounced in patients who responded to treatment [Gupta et al, 2016;Li et al, 2013;Schmidt et al, 2016;Yoshimura et al, 2013]. The findings from those studies are supported by the Strawbridge et al meta-analysis which concluded that TNF-α, but not CRP, decreased in responders.…”

“…The neurotrophic hypothesis explains the occurrence of depressive symptoms as a consequence of disordered neuroplasticity, neurogenesis and resilience caused by diminution of brain-derived neurotrophic factor (BDNF). Animal studies followed by clinical trials confirmed that antidepressant drugs act not only on the neurotransmission but also result in increases of BNDF levels [Gupta et al, 2016].…”

“…The well-established monoamine hypothesis assumes a depletion of neurotransmitters: serotonin (5-HT) and noradrenaline (NA) in certain brain regions [Gupta et al, 2016]. The neurotrophic hypothesis explains the occurrence of depressive symptoms as a consequence of disordered neuroplasticity, neurogenesis and resilience caused by diminution of brain-derived neurotrophic factor (BDNF).…”

“…It is known that experimental administration of interleukins 1β and 6 (IL-1β, IL-6) and tumor necrosis factor alpha (TNF-α) exerts a depressive effect including fatigue, anxiety and somnolence in humans [Gupta et al, 2016;Hashimoto, 2015;Köhler et al, 2014]. In rodents exposed intravenously to lipopolysaccharide (LPS), an inflammatory state occurs resulting in a depressivelike behaviour.…”