Therapeutic targeting of brain arachidonic acid cascade in bipolar disorder by low dose aspirin and celecoxib

•Mood stabilizers with disparate chemical structures and suggested mechanisms of action are approved for treating bipolar disorder•When administered to unanesthetized rats at clinically relevant doses, each of four approved mood stabilizers are reported to downregulate AA turnover and other aspects of the brain AA metabolic cascade•Two large 10-year Dutch and Danish pharmacoepidemiological studies both suggest a significant adjunctive effect of low dose chronic aspirin in bipolar patients; a meta-analysis of three 6-8 week RCTs also indicates a positive adjunctive effect of celecoxib in bipolar patients with acute mania•These basic and clinical observations support the hypothesis that reducing the brain AA metabolic cascade is therapeutic in bipolar disorder, and that chronic low dose aspirin and celecoxib can help in this regard