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No. 1 (2025)

GENERAL THERAPY QUESTIONS AND REVIEWS

Anti-Inflammatory Therapy for Bipolar Disorder: Current State of Evidence

https://doi.org/10.48612/psyph/p3n7-t14h-zdea

Published 2025-03-30

  • А.А. Kasyanova
    • ,
  • О.V. Limankin
    • ,
  • N.N. Petrova

А.А. Kasyanova
Saint-Petersburg University

О.V. Limankin
Saint-Petersburg University; P.P. Kashchenko Saint Petersburg Psychiatric Hospital No. 1; North-Western State Medical University named after I.I. Mechnikov

N.N. Petrova
Saint-Petersburg University

Abstract

Relevance. Numerous studies indicate that immune dysfunction is one of the key causes of the occurrence and progression of bipolar disorder (BD). A significant number of studies have been conducted evaluating the effectiveness of anti-inflammatory drugs in the treatment of BD. The purpose of this descriptive review is to summarize the available systematic reviews and meta-analyses evaluating the effectiveness of anti-inflammatory therapy in BD at all stages of the disorder.

Methods. The search for publications was carried out in the electronic databases MEDLINE and Google Scholar. Additional relevant studies were identified through manual searches of the reference lists of selected articles. We selected publications representing a systematic review (with or without meta-analysis), which evaluated the effects of anti-inflammatory drugs in the treatment of any phase of BD. At the first stage of the study, 704 publications were identified, and 11 publications were included in the final analysis. A descriptive analysis of the selected sources has been performed.

Results. Among the studied anti-inflammatory drugs, N-acetylcysteine was included in six meta-analyses, nonsteroidal anti-inflammatory drugs (NSAIDs) and celecoxib in five meta-analyses, omega-3 polyunsaturated fatty acids (PUFAs) in three meta-analyses, coenzyme Q10 in one meta-analysis, minocycline in two meta-analyses, and antiglucocorticoid drugs (methirapone, ketoconazole, mifepristone) in three meta-analyses. As a result of the generalization of available systematic reviews and meta-analyses evaluating the effectiveness of anti-inflammatory therapy in BD at all stages of the disease, the most significant antidepressant effect was observed in N-acetylcysteine, which was used as an augmentation to standard therapy. NSAIDs and celecoxib have a moderate antidepressant effect, but the data are heterogeneous. A significant reduction in manic symptoms was observed only in celecoxib. The use of minocycline and infliximab has not demonstrated sufficient results regarding the treatment of various phases of BD, however, in patients with signs of inflammation — elevated levels of C-reactive protein and IL-6 — these drugs may be effective, warranting further investigation. Antiglucocorticoid drugs have shown promising results only in patients with high cortisol levels, so their use in clinical practice also requires further research. Current data is insufficient to draw definitive conclusions regarding the effectiveness of omega-3 PUFAs and coenzyme Q10. In all included studies, most anti-inflammatory drugs, including N-acetylcysteine, NSAIDs, celecoxib, and minocycline, had a favorable tolerability profile, and side effects were comparable to those in the placebo group.

Conclusions. The data presented in systematic reviews and meta-analyses indicate the potential effectiveness of some anti-inflammatory drugs in the treatment of BD, especially N-acetylcysteine and celecoxib. Taking into account baseline levels of inflammatory markers can serve to identify patients who can benefit most from anti-inflammatory therapy. The heterogeneity of the results and the limited data require further high-quality studies with large samples to confirm the effectiveness and safety of anti-inflammatory drugs in the treatment of BD.

Keywords

bipolar disorder, mania, depression, treatment augmentation, inflammation, anti-inflammatory drugs

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