Antidepressant psychopharmacology: is inflammation a future target?

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.