Anti-inflammatory Drugs in the Treatment of Depression

The last two decades have seen a flourishing of research into the immunobiology of psychiatric phenotypes, in particular major depressive disorder. Both preclinical and clinical data have highlighted pathways and possible mechanisms that might link changes in immunobiology, most especially inflammation, to clinically relevant behaviour. From a therapeutics perspective, a major impetus has been the action of Biologics, often monoclonal antibodies, that target specific cytokines acting as “molecular scalpels” helping to uncover the actions of those proteins. These interventions have been associated with improvements in mood and related symptoms. There are now enough studies and participants to permit meta-analytic analyses of the actions of these and other anti-inflammatory agents. In this chapter, the focus is on the evidence for the role of inflammation biology in depression and the meta-analytic data from trials. The putative mechanisms that might underpin the antidepressant effect of anti-inflammatory drugs are also explored. Lastly, I describe the more stubborn difficulties around heterogeneity, deep phenotyping and stratification as well as improved animal models and greater understanding of the biology that might be addressed by future studies.