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Can Anti-Inflammatory Agents Be Used to Treat Bipolar Depression?

September 26, 2017
Vladimir Maletic

In this occasional feature on Psych Congress Network, members of the Psych Congress Steering Committee answer questions asked by audience members at Psych Congress meetings.

QUESTION: Have anti-inflammatory agents been studied in treating bipolar depression? 

ANSWER: An excellent question. Both depression and mania have been associated with elevation in the peripheral inflammatory cytokines. Furthermore, one study has noted that an increase in a composite inflammatory cytokine measure, comprised of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), preceded the onset of mania. Additionally, peripheral inflammatory cytokine levels may reflect illness duration. While patients who have suffered from bipolar disorder for less than three years show no elevation in inflammatory cytokines relative to healthy controls, there is a robust difference in patients who have had bipolar disorder for longer than 10 years. These findings lend credence to an assumed etiological role of inflammatory cytokines in pathophysiology of bipolar disorder. It is also plausible to believe that increased peripheral inflammatory signaling may contribute to comorbid cardiometabolic and inflammatory derangements (including migraine headaches) in people with bipolar disorder.

Is there any indication of increased inflammatory signaling in the brain of patients with bipolar disorder? The short answer is, yes! A small study has found a significant difference in central nervous system (CNS) levels of Interleukin-1 (IL-1) in bipolar patients, relative to healthy controls.

So, when everything is said and done, should we deploy anti-inflammatory strategies in the treatment of bipolar illness? Unfortunately, a relative lack of large, methodologically sound, controlled studies invites some caution. A recent meta-analysis found only a moderate benefit in adjunct use of varied anti-inflammatory strategies (nonsteroidal agents, omega-3 fatty acids, N-acetylcysteine, and pioglitazone) in treatment of bipolar depression.

Minocycline, a tetracyclic antibiotic, has been shown to prevent inflammatory cytokine release and microglial activation in the CNS. A pilot study has indicated benefits from adjunct minocycline use in treatment of bipolar depression, especially in individuals who have suffered from early life adversity.

In conclusion, due to a lack of replicated large-scale, longitudinal, randomized controlled trials, adjunct use of anti-inflammatory strategies for treatment of bipolar illness may not be ready for prime-time. But findings of the early exploratory studies are encouraging, so stay tuned!

— Vladimir Maletic, MD, MS, Clinical Professor of Psychiatry and Behavioral Science, University of South Carolina School of Medicine, Greenville


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