Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects a systematic review and meta-analysis of randomized clinical trials

  • Köhler O
  • E. Benros M
  • Nordentoft M
 et al. 
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Abstract

Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. OBJECTIVE To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions. DATA SOURCES Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles. STUDY SELECTION Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. DATA EXTRACTION AND SYNTHESIS Datawere extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated. MAIN OUTCOMES AND MEASURES Depression scores after treatment and adverse effects. RESULTS Ten publications reporting on 14 trials (6262 participants)were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 4258) and 4 investigated cytokine inhibitors (n = 2004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95%CI, -0.57 to -0.11; I2 = 90%) compared with placebo. This effectwas observed in studies including patients with depression (SMD, -0.54; 95%CI, -1.08 to -0.01; I2 = 68%) and depressive symptoms (SMD, -0.27; 95%CI, -0.53 to -0.01; I2 = 68%). The heterogeneity of the studieswas not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95%CI, -0.49 to -0.08; I2 = 73%) on remission (OR, 7.89; 95%CI, 2.94 to 21.17; I2 = 0%) and response (OR, 6.59; 95%CI, 2.24 to 19.42; I2 = 0%). Among the 6 studies reporting on adverse effects,we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6weeks or infections after 12weeks of anti-inflammatory treatment compared with placebo. All trialswere associated with a high risk of bias owing to potentially compromised internal validity. CONCLUSIONS AND RELEVANCE Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted. ©2014 American Medical Association. All rights reserved.

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Authors

  • Michael BenrosMental Health Centre Copenhagen

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  • Ole Köhler

  • Merete Nordentoft

  • Michael E. Farkouh

  • Rupa L. Iyengar

  • Ole Mors

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