Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis

Rosenblat, J.D., Kakar, R., Berk, M., Kessing, L.V., Vinberg, M., Baune, B.T., Mansur, R.B., Brietzke, E., Goldstein, B.I. and McIntyre, R.S. 2016, Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis, Bipolar disorders, vol. 18, no. 2, pp. 89-101, doi: 10.1111/bdi.12373.

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Title Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis
Author(s) Rosenblat, J.D.
Kakar, R.
Berk, M.ORCID iD for Berk, M.
Kessing, L.V.
Vinberg, M.
Baune, B.T.
Mansur, R.B.
Brietzke, E.
Goldstein, B.I.
McIntyre, R.S.
Journal name Bipolar disorders
Volume number 18
Issue number 2
Start page 89
End page 101
Total pages 13
Publisher Wiley
Place of publication London, Eng.
Publication date 2016-03
ISSN 1399-5618
Keyword(s) aspirin
bipolar disorder
N-acetylcysteine (NAC)
nonsteroidal anti-inflammatory drugs (NSAIDs)
omega 3 polyunsaturated fatty acids
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
Summary OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
Language eng
DOI 10.1111/bdi.12373
Field of Research 1103 Clinical Sciences
1109 Neurosciences
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Wiley
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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