Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects

Köhler, Ole; Benros, Michael E.; Nordentoft, Merete; Farkouh, Michael E.; Iyengar, Rupa; Mors, Ole; Krogh, Jesper

doi:10.1001/jamapsychiatry.2014.1611

Cited by 788 publications

(344 citation statements)

References 53 publications

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“…interleukin (IL)-6, IL-1 and tumor necrosis factor (TNF)α, and signs of an acute phase response [2,3]. Recently, a systematic review and a meta-analysis showed that antiinflammatory drugs may have antidepressant effects [4,5]. The latter authors state that because there is an inflammatory state in depression, anti-inflammatory drugs were examined, and that the results of their meta-analysis are proof of concept that anti-inflammatory drugs are useful in depression.…”

Section: Introductionmentioning

confidence: 99%

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

et al. 2015

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Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g. C-reactive protein, and pro-inflammatory cytokines, e.g. interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways.Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g. activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, activation of the Toll-like Receptor and neuroprogressive pathways. Thirdly, antiinflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e. path and drug discovery processes, omics-based techniques and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics and microbiomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular 4 networks, pathways and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.

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Section: Introductionmentioning

confidence: 99%

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

et al. 2015

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“…A recent metaanalysis included 6262 patients with depression treated with anti-inflammatory substances and showed a beneficial overall effect on depressive symptoms [84] (see Fig. 2).…”

Section: Treat Inflammation In Depressionmentioning

confidence: 99%

“…Nonsteroidal anti-inflammatory drugs were associated with a better antidepressant effect in general, with 9 of 10 trials favoring NSAIDs, whereas a statistical trend was observed favoring cytokine inhibitors among 4 studies, but the results remained heterogeneous [84]. All randomized studies emphasized the adjunctive antidepressant effects of celecoxib within the first 6 to 8 weeks of antidepressant treatment, which was most pronounced among patients with increased proinflammatory markers [84]. In this context, it is possible, that specific subgroups would benefit more from anti-inflammatory intervention, such as patients with low-grade inflammation or comorbid inflammatory diseases [84].…”

Section: Treat Inflammation In Depressionmentioning

confidence: 99%

“…All randomized studies emphasized the adjunctive antidepressant effects of celecoxib within the first 6 to 8 weeks of antidepressant treatment, which was most pronounced among patients with increased proinflammatory markers [84]. In this context, it is possible, that specific subgroups would benefit more from anti-inflammatory intervention, such as patients with low-grade inflammation or comorbid inflammatory diseases [84]. Anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increasing the risk of adverse effects [84].…”

Section: Treat Inflammation In Depressionmentioning

confidence: 99%

“…In this context, it is possible, that specific subgroups would benefit more from anti-inflammatory intervention, such as patients with low-grade inflammation or comorbid inflammatory diseases [84]. Anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increasing the risk of adverse effects [84]. Identification of subgroups that could benefit from such treatment might be warranted [84].…”

Section: Treat Inflammation In Depressionmentioning

confidence: 99%

See 2 more Smart Citations

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

Lang¹,

Walter²

2017

Neurosignals

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The depressive state has been characterised as one of elevated inflammation, changed cardiovascular parameters and a deranged metabolic situation all of which holds promise for a better understanding and handling of treatment-resistance in affective disorders as well as for future developments in treatment algorithms. In this context several biomarkers are differentially regulated by antidepressant treatment and connected to metabolic, inflammatory, cardiovascular and apoptotic components of the pathophysiology, i.e. adiponectin, apolipoprotein-B, B-type natriuretic peptide, cortisol, CRP, cysteine, homocysteine, fibrinogen, adiponectin, BMI, glycated hemoglobin A1c, leptin, interferon-gamma, high-density lipoprotein, interleukin interleukin-1alpha, -1beta, -2, -4, -5, -6, -8, -10, -12, -13, -17, insulin-like growth factor-1, low-density lipoprotein, myeloperoxidase, osteoprotegerin, tumour necrosis factor alpha, troponins, triglycerides etc. In this context antidepressants exert different modulatory effects on the outcome, incidence and mortality concerning several severe disorders, i.e. cancer, diabetes, stroke, inflammation, stroke and cardiovascular risk. Vice versa different drugs used in the treatment of these disorders have a favourable effect in depressive states, e.g. statins, aspirine, NSAIDs, pioglitazone, celecoxib, peroxisome proliferator-activated receptor-gamma agonists and minocycline. In this review, actions of different antidepressant treatment strategies on cancer, stroke, diabetes and cardiovascular disorders are shown and the influence on the outcome of the disorders is differentially discussed. In conclusion a hypothetic model for the implication of actual findings in everyday clinical practice is proposed. In this context personalized treatment could be used to tailor treatment to specific individuals according to their clinical endophenotypes. Moreover a potential target for the development of novel intervention strategies might be used.

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Medications With Depression as an Adverse Effect

Agustini

Berk

2018

JAMA

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Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects

Cited by 788 publications

References 53 publications

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

Medications With Depression as an Adverse Effect

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