Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment

Publisher: Bentham Science Publishers

E-ISSN: 1875-6190|14|7|674-687

ISSN: 1570-159X

Source: Current Neuropharmacology, Vol.14, Iss.7, 2016-08, pp. : 674-687

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Abstract

Growing evidence supports a mutual relationship between inflammationand major depression. A variety of mechanisms are outlined, indicating howinflammation may be involved in the pathogenesis, course and treatment of majordepression. In particular, this review addresses 1) inflammatory cytokines as markersof depression and potential predictors of treatment response, 2) findings thatcytokines interact with antidepressants and non-pharmacological antidepressivetherapies, such as electroconvulsive therapy, deep brain stimulation and physicalactivity, 3) the influence of cytokines on the cytochrome (CYP) p450-system anddrug efflux transporters, and 4) how cascades of inflammation might serve asantidepressant drug targets. A number of clinical trials have focused on agents withimmunmodulatory properties in the treatment of depression, of which this review covers nonsteroidalanti-inflammatory drugs (NSAIDs), cytokine inhibitors, ketamine, polyunsaturated fatty acids, statins andcurcumin. A perspective is also provided on possible future immune targets for antidepressant therapy,such as toll-like receptor-inhibitors, glycogen synthase kinase-3 inhibitors, oleanolic acid analogs andminocycline. Concluding from the available data, markers of inflammation may become relevant factorsfor more personalised planning and prediction of response of antidepressant treatment strategies. Agentswith anti-inflammatory properties have the potential to serve as clinically relevant antidepressants.Further studies are required to better define and identify subgroups of patients responsive to inflammatoryagents as well as to define optimal time points for treatment onset and duration.