Journal
BIPOLAR DISORDERS
Volume 18, Issue 2, Pages 89-101Publisher
WILEY
DOI: 10.1111/bdi.12373
Keywords
aspirin; bipolar disorder; depression; inflammation; infliximab; minocycline; N-acetylcysteine (NAC); nonsteroidal anti-inflammatory drugs (NSAIDs); omega 3 polyunsaturated fatty acids; pioglitazone
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Funding
- NHMRC Senior Principal Research Fellowship [1059660]
- 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
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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.
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