Depression has been shown to be associated with systemic inflammatory activity and the mode of action of several antidepressants appears to involve immunomodulation. Effects on immune system activity have also recently been observed in correlation with therapeutic response to mirtazapine in cardiac patients with depression, but no study has yet examined these effects in otherwise physically healthy depressed patients treated with mirtazapine. This report describes an association between a clinical antidepressant response and a decrease in markers of systemic inflammation observed during pharmacotherapy with mirtazapine in a severely depressed but physically well patient. This observation adds to the evidence that changes in inflammatory responses may be implicated in the mode of action of antidepressants. Further studies of antidepressant responses to mirtazapine and levels of inflammatory markers in depressed patients without medical comorbidity can help elucidate the role of the immune system in the pathophysiology of depression, and hence contribute to the development of novel antidepressant therapies. 1. Introduction Major depressive disorder (MDD) is a complex illness associated with immune system involvement and a systemic inflammatory response [1], including elevated C-reactive protein (CRP) and plasma immunomodulatory cytokine levels [2, 3]. It has been demonstrated that neurocytokines can induce “sickness behavior,” which mirrors the core biological and behavioural symptoms of clinical depression [4]. There is growing evidence that not only tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) but also newer noradrenergic and specific serotonergic antidepressants (NaSSAs) such as mirtazapine may modulate the inflammatory response as part of their mode of action [5]. Reduction in the levels of inflammatory markers such as CRP, the Erythrocyte Sedimentation Rate (ESR), and White Cell Count (WCC) has been observed in direct response to SSRI treatment, although it remains unclear how this relates to the therapeutic effect of antidepressants [6]. A recent study of mirtazapine treatment of postmyocardial infarction depression found a strong association between antidepressant response to mirtazapine and its effects on systemic inflammation as measured by soluble Tumour Necrosis Factor Receptor-1 (sTNF-R1) levels [7]. However, little is known about inflammatory responses to mirtazapine in depressed patients without physical comorbidity. We describe a patient with a severe depressive episode and no history or evidence of
References
[1]
A. H. Miller, V. Maletic, and C. L. Raison, “Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression,” Biological Psychiatry, vol. 65, no. 9, pp. 732–741, 2009.
[2]
T. G. Dinan, “Inflammatory markers in depression,” Current Opinion in Psychiatry, vol. 22, no. 1, pp. 32–36, 2009.
[3]
M. B. Howren, D. M. Lamkin, and J. Suls, “Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis,” Psychosomatic Medicine, vol. 71, no. 2, pp. 171–186, 2009.
[4]
R. Dantzer, L. Capuron, M. R. Irwin et al., “Identification and treatment of symptoms associated with inflammation in medically ill patients,” Psychoneuroendocrinology, vol. 33, no. 1, pp. 18–29, 2008.
[5]
D. de Berardis, C. M. V. Conti, N. Serroni et al., “The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature,” International Journal of Immunopathology and Pharmacology, vol. 23, no. 2, pp. 417–422, 2010.
[6]
N. Chavda, N. D. Kantharia, and Jaykaran, “Effects of fluoxetine and escitalopram on C-reactive protein in patients of depression,” Journal of Pharmacology and Pharmacotherapeutics, vol. 2, no. 1, pp. 11–16, 2011.
[7]
D. M. Tulner, O. R. F. Smith, A. Schins et al., “Antidepressive effect of mirtazapine in post-myocardial infarction depression is associated with soluble TNF-R1 increase: data from the MIND-IT,” Neuropsychobiology, vol. 63, no. 3, pp. 169–176, 2011.
[8]
J. Zhu, X. Wei, J. Liu, Y. Hu, and J. Xu, “Interaction of glia activation and neurotransmission in hippocampus of neuropathic rats treated with mirtazapine,” Experimental and Clinical Psychopharmacology, vol. 17, no. 3, pp. 198–203, 2009.
[9]
S. M. O'Brien, L. V. Scott, and T. G. Dinan, “Antidepressant therapy and C-reactive protein levels,” British Journal of Psychiatry, vol. 188, pp. 449–452, 2006.
[10]
J. Hannestad, N. Dellagioia, and M. Bloch, “The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis,” Neuropsychopharmacology, vol. 36, no. 12, pp. 2452–2459, 2011.
[11]
W. K. Lagrand, C. A. Visser, W. T. Hermens et al., “C-reactive protein as a cardiovascular risk factor more than an epiphenomenon?” Circulation, vol. 100, no. 1, pp. 96–102, 1999.
[12]
R. Sharma, M. Rauchhaus, P. P. Ponikowski et al., “The relationship of the erythrocyte sedimentation rate to inflammatory cytokines and survival in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors,” Journal of the American College of Cardiology, vol. 36, no. 2, pp. 523–528, 2000.
[13]
R. Krishnadas and J. Cavanagh, “Depression: an inflammatory illness?” Journal of Neurology, Neurosurgery and Psychiatry, vol. 83, no. 5, pp. 495–502, 2012.
[14]
Z. Rogóz, G. Skuza, and B. Legutko, “Repeated treatment with mirtazapine induces brain-derived neurotrophic factor gene expression in rats,” Journal of Physiology and Pharmacology, vol. 56, no. 4, pp. 661–671, 2005.
