Title:Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment
Volume: 14
Issue: 7
Author(s): Frank M. Schmidt, Kenneth C. Kirkby and Nicole Lichtblau
Affiliation:
Keywords:
Biomarker, cytokines, curcumin, depression, infliximab, ketamine, treatment prediction.
Abstract: Growing evidence supports a mutual relationship between inflammation
and major depression. A variety of mechanisms are outlined, indicating how
inflammation may be involved in the pathogenesis, course and treatment of major
depression. In particular, this review addresses 1) inflammatory cytokines as markers
of depression and potential predictors of treatment response, 2) findings that
cytokines interact with antidepressants and non-pharmacological antidepressive
therapies, such as electroconvulsive therapy, deep brain stimulation and physical
activity, 3) the influence of cytokines on the cytochrome (CYP) p450-system and
drug efflux transporters, and 4) how cascades of inflammation might serve as
antidepressant drug targets. A number of clinical trials have focused on agents with
immunmodulatory properties in the treatment of depression, of which this review covers nonsteroidal
anti-inflammatory drugs (NSAIDs), cytokine inhibitors, ketamine, polyunsaturated fatty acids, statins and
curcumin. 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 and
minocycline. Concluding from the available data, markers of inflammation may become relevant factors
for more personalised planning and prediction of response of antidepressant treatment strategies. Agents
with 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 inflammatory
agents as well as to define optimal time points for treatment onset and duration.
