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

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

Author Rosenblat, Joshua D. Google Scholar
Kakar, Ron Google Scholar
Berk, Michael Google Scholar
Kessing, Lars V. Google Scholar
Vinberg, Maj Google Scholar
Baune, Bernhard T. Google Scholar
Mansur, Rodrigo B. Autor UNIFESP Google Scholar
Brietzke, Elisa Autor UNIFESP Google Scholar
Goldstein, Benjamin I. Google Scholar
McIntyre, Roger S. Google Scholar
Abstract ObjectiveInflammation 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. MethodsCompleted 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 Clinicaltrials.gov 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. ResultsTen 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 (I-2 = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. ConclusionsOverall, 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.
Keywords aspirin
bipolar disorder
depression
inflammation
infliximab
minocycline
N-acetylcysteine (NAC)
nonsteroidal anti-inflammatory drugs (NSAIDs)
omega 3 polyunsaturated fatty acids
pioglitazone
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor NHMRC Senior Principal Research Fellowship
National Institutes of Health
Cooperative Research Centre
Simons Autism Foundation
Cancer Council of Victoria
Stanley Medical Research Foundation
MBF
NHMRC
Beyond Blue
Rotary Health
Geelong Medical Research Foundation
Bristol-Myers Squibb
Eli Lilly Co.
GlaxoSmithKline
Meat and Livestock Board
Organon
Novartis
Mayne Pharma
Servier
Woolworths
National Health and Medical Research Council Australia
James and Diana Ramsay Foundation
Rebecca L Cooper Medical Research Foundation
Australian Rotary Health
CNPq (Brazil)
FAPESP (Brazil)
CAPES (Brazil)
Lundbeck
AstraZeneca
Pfizer
Shire
Otsuka
National Institute of Mental Health
Stanley Medical Research Institute
Canadian Institutes for Health Research
Brain and Behavior Research Foundation
Janssen Ortho
Sunovion
Takeda
Forest
Grant number NHMRC Senior Principal Research Fellowship: 1059660
Date 2016
Published in Bipolar Disorders. Hoboken, v. 18, n. 2, p. 89-101, 2016.
ISSN 1398-5647 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 89-101
Origin http://dx.doi.org/10.1111/bdi.12373
Access rights Closed access
Type Article
Web of Science ID WOS:000373124400001
URI https://repositorio.unifesp.br/handle/11600/57859

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