Antidepressant psychopharmacology: is inflammation a future target?

Abstract

Raised inflammatory setpoints have been associated with major depression and its detrimental consequences on brain function, as they lead to increased production of cytokines, changes in gene expression and activated brain microglia. Three main lines of evidence support immune-inflammatory mechanisms as targets for the treatment of depression. First, higher inflammation hampers response to antidepressants, and effective antidepressant treatment decreases inflammation. Second, conventional antidepressants share immune-modulatory and anti-inflammatory properties, which could affect inflammation during the depression. Third, anti-inflammatory and immune-modulatory treatments proved superior to placebo in randomized controlled antidepressant trials. New targets and new pharmacologic treatment for immune-mediated inflammatory diseases have been identified and tested in several medical settings and interest is warranted for testing them as antidepressants.

Post-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment

“…In this context, future pharmacological research is needed to investigate whether the antidepressant efficacy would be paired with a reduction of inflammation, thus reversing the inflammation triggered by the infection. Anti-inflammatory drugs and immunomodulators that are currently being tested for treatment-resistant MDD and that have proved efficacious in reducing depressive symptoms in patients with inflammation could prove useful for inflammation-induced depressive episodes both as prevention and as a treatment strategy [ 186 ]. Moreover, the potential effect of non-pharmacological interventions such as light therapy, non-invasive somatic stimulation, horticultural therapy, and nutraceuticals should be explored [ 187 – 189 ].…”

Unhealthy lifestyle impacts on biological systems involved in stress response: hypothalamic–pituitary–adrenal axis, inflammation and autonomous nervous system

“…Medications may have a complex effect on lifestyle and inflammation, antidepressants may decrease inflammation and increase activity in depression but also potentially induce weight gain; therefore, a concomitant psychoeducation treatment is strongly suggested ( El-Khoury et al , 2020 ; Hidalgo-Mazzei et al , 2020 ; Benedetti et al , 2022 ; Dörks et al , 2022 ).…”

Biology of cyclooxygenase-2: An application in depression therapeutics

“…In recent years, an increasing number of scholars have found that neuroinflammation is an important pathological factor triggering central neurological disorders such as depression, and inhibiting central neuroinflammation is a key way to effectively alleviate the onset and progression of depression (12)(13)(14)(15)(16). It was found that upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) was seen in the hippocampus and cortex of Lipopolysaccharide (LSP)-induced depressed mice (17).…”