The efficacy of anti-inflammatory treatment interventions on depression in individuals with major depressive disorder and high levels of inflammation: A systematic review of randomized clinical trials

Background: Studies evaluating the efficacy of anti-inflammatory treatment strategies for major depressive disorder (MDD) commonly include participants who do not demonstrate elevated concentrations of baseline inflammatory mediators, or simply fail to assess baseline inflammation. This may result in an underestimation of the efficacy of such treatment strategies. Sampling and methods: This systematic review included randomized controlled trials related to the use of anti-inflammatory treatment strategies in individuals who demonstrate elevated concentrations of inflammatory mediators, identified by searching OVID MEDLINE, OVID EMBASE, and OVID PsychINFO. Results: Fifty-one randomized controlled trials were identified via a title and abstract screen, of which 43 were excluded following full-text screening. Of the 8 included trials (n = 437), 5 utilized anti-inflammatory pharmaceuticals, 2 utilized omega-3 fatty acids, and 1 utilized exercise and meditation. Among these studies, only the trial related to exercise and meditation demonstrated both an elevation in baseline inflammation, and a significant reduction in inflammation following intervention. Issues related to insufficient interventions and/or lack of reporting of inflammatory mediators at one or more time-points were common. Conclusion: Among the growing number of studies which examine the potential antidepressant benefit of anti-inflammatory treatment strategies, few have studied populations which demonstrate elevated baseline concentrations. Further, studies commonly fail to induce significant changes in inflammation following intervention. Together, this may explain the low efficacy frequently reported with such interventions. Future studies which utilize both stronger interventions (sufficient to reduce levels of inflammation), and participants with elevated baseline concentrations, may produce a more substantial influence on symptoms of (MDD).