Effect of Anti-inflammatory Treatment On Depression, Depressive Symptoms and Side Effects: a Systematic Review and Meta-analysis of Randomized Clinical Trials

Abstract

Introduction Studies have indicated antidepressant effects of anti-inflammatory treatment; however, results have been conflicting and side effects may contraindicate anti-inflammatory treatment. Objectives To systematically review the antidepressant and possible side effects of anti-inflammatory interventions. Aims To include trials published prior to December, 31st 2013, and evaluate depression scores after treatment and side effects. Methods We identified randomized, placebo-controlled trials assessing efficacy and side effects of pharmacological anti-inflammatory treatment in adults with depressive symptoms including adults fulfilling depression-criteria. We calculated standard mean difference (SMD) and Odds ratios (OR). Results 10 publications covering 14 trials (n=6,262) were included: 10 on non-steroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and four on cytokine-inhibitors (n=2,004). Anti-inflammatory treatment reduced 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=93%). Sub-analyses particularly emphasized antidepressant properties for the selective cyclooxygenase-2 inhibitor celecoxib in general (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 6 studies (n=2,523), we found no evidence of an increased number of gastrointestinalor cardiovascular events after 6 weeks nor infections after 12 weeks of anti-inflammatory treatment. All trials were associated with high risk of bias. Conclusions Anti-inflammatory treatment, in particular celecoxib, decreased depressive symptoms without increased risks of side effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit hereof might be warranted.