Anti-inflammatory properties of commonly used psychiatric drugs

Abstract

Mental health and neurodevelopmental disorders are extremely common across the lifespan and are characterized by a complicated range of symptoms that affect wellbeing. There are relatively few drugs available that target disease mechanisms for any of these disorders. Instead, therapeutics are focused on symptoms and syndromes, largely driven by neurotransmitter hypotheses, such as serotonin or dopamine hypotheses of depression. Emerging evidence suggests that maternal inflammation during pregnancy plays a key role in neurodevelopmental disorders, and inflammation can influence mental health expression across the lifespan. It is now recognized that commonly used psychiatric drugs (anti-depressants, anti-psychotics, and mood stabilizers) have anti-inflammatory properties. In this review, we bring together the human evidence regarding the anti-inflammatory mechanisms for these main classes of psychiatric drugs across a broad range of mental health disorders. All three classes of drugs showed evidence of decreasing levels of pro-inflammatory cytokines, particularly IL-6 and TNF-α, while increasing the levels of the anti-inflammatory cytokine, IL-10. Some studies also showed evidence of reduced inflammatory signaling via nuclear factor- (NF-)κB and signal transducer and activator of transcription (STAT) pathways. As researchers, clinicians, and patients become increasingly aware of the role of inflammation in brain health, it is reassuring that these psychiatric drugs may also abrogate this inflammation, in addition to their effects on neurotransmission. Further studies are required to determine whether inflammation is a driver of disease pathogenesis, and therefore should be a therapeutic target in future clinical trials.

Keywords: anti-depressants; anti-psychotics; inflammation; mental health; mood stabilizers.

Figure 1

Common signaling pathways. TLRs are activated by various stimuli, commonly recognizing viral and bacterial products, or host-derived endogenous compounds (i.e., DAMPs or PAMPs, respectively). Triggering of TLRs can activate multiple pathways which produce complexes that activate the IKK structure (comprising catalytic IKKα and IKKβ, and regulatory IKKγ subunits). NF-κB is produced and either translocates to the nucleus or is negatively regulated by phosphorylation of IκB. In the nucleus, NF-κB influences the expression of many inflammatory genes, in turn affecting production of cytokines, chemokines, adhesion molecules, and costimulatory molecules. Activation of the JAK/STAT pathway via cytokine receptors also contributes to NF-κB signaling and alterations in the expression of inflammatory genes. JAK, Janus kinase; STAT, signal transducer and activator of transcription; TLR, toll-like receptor; DAMP, damage-associated molecular patterns; PAMP, pathogen-associated molecular pattern; MyD88, myeloid differentiation primary response 88; IKK, inhibitor of κB kinase; IRAK, interleukin receptor-associated kinase; TRAF, tumor necrosis factor receptor-associated factor; IκB, inhibitor of nuclear factor κB; NF-κB, nuclear factor κB; TNF, tumor necrosis factor; IL, interleukin; CCL, CC motif chemokine ligand;; CXCL, CXC motif chemokine ligand; ICAM, intercellular adhesion molecule; VCAM, vascular cell adhesion molecule; CD, cluster of differentiation. Figure adapted from “TLR Signaling Pathway”, by BioRender.com (2015). Retrieved from: https://app.biorender.com/biorender-templates.