Acetylsalicylic acid and its metabolite gentisic acid may act as adjunctive agents in the treatment of psychiatric disorders

Neuropsychiatric disorders place a very high burden on the global health and economy. The efficacies of currently available drugs in the psychiatric armamentarium are suboptimal and almost all of them target several neurotransmitter pathways. But it is more and more recognized that the neuroinflammation and associated oxidative pathways are important players in the etiopathogenesis of psychiatric disorders. In parallel to this new concept, recent investigations indicate that adjunction of acetylsalicylic acid (ASA) to the orthodox psychiatric treatments augments therapeutic efficacy in bipolar disorder and schizophrenia. Gentisic acid is a redox active quinonoid ASA metabolite and an endogenously produced siderophore with much more potent antioxidant effects than its parent compound. Moreover, it harbours molecular features that provide its selective conversion to even more potent anti-inflammatory quinonoid molecules within the inflammatory micromilieu. We believe that ASA alone and its combination with gentisic acid should be studied in animal models of psychiatric disorders to reveal their potential in regard to the augmentation of currently available treatments. If several animal studies prove their potential, clinical trials could easily be conducted, as both ASA and gentisic acid have a relatively high biosafety and a long history of clinical use.