Taking the fuel out of the fire: Evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders

Background: Inflammation has emerged as a potentially important factor - and thus putative pharmacological target - in the pathology of bipolar disorders. However to date no systematic evaluations of the efficacy of add on anti-inflammatory treatment for the depressive and manic episodes have been carried out.

Methods: Sixteen articles were ultimately identified - by computer searches of databases (including PsycINFO, MEDLINE, and EMBASE), supplemented by hand searches and personal communication - as meeting study inclusion criteria.

Results: Anti-manic effects were evaluated in two trials, one of adjunctive n-acetyl cysteine (NAC), one of omega-3 fatty acids (O3FA), and significant improvements only emerged for NAC. Celecoxib had a rapid but short-lived antidepressant effect. Despite limited effects of O3FA on symptoms, imaging data demonstrated alterations in neuronal functioning that might have longer-term therapeutic effects. Evidence was strongest for adjunctive NAC in bipolar depression though conclusions are limited by small sample sizes.

Limitations: Definitive conclusions are limited by the paucity of data, small study sizes, and the variability in methodology used.

Conclusions: Current evidence for aspirin or celecoxib is insufficient though further investigation of the potential of celecoxib in early illness onset is warranted. Variable evidence exists for add-on O3FA though an indication of short-term treatment effects on membrane fluidity and neuronal activity suggest longer follow-up assessment is needed. The strongest evidence emerged for NAC in depression and future studies must address the role of illness duration and patients' baseline medications on outcomes. Careful consideration of lithium toxicity in the elderly and renal impaired is essential.