Abstract
Background
No study has gathered evidence from all randomized clinical trials (RCTs) with anti‐inflammatory drugs measuring antidepressant effects including a detailed assessment of side effects and bias.
Methods
We performed a systematic review identifying RCTs published prior to January 1, 2018 studying antidepressant treatment effects and side effects of pharmacological anti‐inflammatory intervention in adults with major depressive disorder (MDD) or depressive symptoms. Outcomes were depression scores after treatment, remission, response and side effects. Pooled standard mean differences (SMD) and risk ratios (RR) including 95%‐confidence intervals (95%‐CI) were calculated.
Results
We identified 36 RCTs, whereof 13 investigated NSAIDs (N=4,214), 9 cytokine‐inhibitors (N=3,345), 7 statins (N=1,576), 3 minocycline (N=151), 2 pioglitazone (N=77), and 2 glucocorticoids (N=59). Anti‐inflammatory agents improved depressive symptoms compared to placebo as add‐on in patients with MDD (SMD=‐0.64; 95%‐CI=‐0.88, ‐0.40; I2=51%; N=597) and as monotherapy (SMD=‐0.41; 95%‐CI=‐0.60, ‐0.22; I2=93%, N=8,825). Anti‐inflammatory add‐on improved response (RR=1.76; 95%‐CI=1.44‐2.16; I2=16%; N=341) and remission (RR=2.14; 95%‐CI=1.03‐4.48; I2=57%; N=270). We found a trend towards an increased risk for infections and all studies showed high risk of bias.
Conclusion
Anti‐inflammatory agents improved antidepressant treatment effects. Future RCTs need to include longer follow‐up, identify optimal doses and subgroups of patients that can benefit from anti‐inflammatory intervention.
This article is protected by copyright. All rights reserved.