The anti-inflammation pharmacodynamics of lithium: Therapy of bipolar disorder.

This article focuses on the anti-inflammatory pharmacodynamics of lithium in the treatment of bipolar disorder (BD), a severe mental illness characterized by mood episodes and high suicide risk. It reviews evidence supporting the inflammatory theory of BD, which links the disorder to dysregulated immune responses and elevated pro-inflammatory cytokines, and explains how lithium exerts therapeutic effects primarily by inhibiting glycogen synthase kinase-3β (GSK-3β). Through this inhibition, lithium reduces the secretion of pro-inflammatory mediators and modulates multiple downstream pathways—including the arachidonic acid, nitric oxide synthase, neurotransmitter, microglial activation, oxidative stress, hypothalamic-pituitary-adrenal (HPA) axis, and microbiota–gut–brain axis pathways—thereby alleviating neuroinflammation and mood symptoms. The article also discusses lithium's clinical advantages over selective COX-2 inhibitors, its limitations such as a narrow therapeutic window, and acknowledges that BD's pathogenesis is multifactorial, involving genetic, environmental, and neurodegenerative factors beyond inflammation.