Pharmacologic implications of inflammatory comorbidity in bipolar disorder

Bipolar disorder (BD) is a chronic illness associated with significant morbidity and mortality. Epidemiological studies have established a strong association between BD and inflammatory comorbidities. Furthermore, illness course is more severe and treatment resistant in BD with comorbid inflammatory disease and vice versa. Immune dysfunction has therefore been proposed as a key pathophysiological nexus sub-serving the bidirectional interaction between BD and inflammatory comorbidities. The foregoing observations have provided the rational and impetus for repurposing anti-inflammatory agents for the treatment of BD. Clinical trials have shown promising results for a variety of mechanistically diverse anti-inflammatory agents. N-Acetylcysteine, infliximab, pioglitazone, celecoxib, aspirin, and omega-3 polyunsaturated fatty acids have shown an antidepressant effect in BD when administered adjunctively to conventional treatments. Currently, insufficient evidence exists to support the routine use of anti-inflammatory agents in the treatment of BD with inflammatory comorbidities; however, several more clinical trials are current underway which may guide clinical application in the near future. Anti-inflammatory agents will likely be most useful for the subpopulation of BD where immune dysfunction is a driving pathogenic factor, such as in patients with inflammatory comorbidities. Future studies are striving to stratify subjects based on immune function or dysfunction in order to better understand which subset of BD subjects will benefit most from anti-inflammatory therapies.