Efficacy of anti‐inflammatory treatment on major depressive disorder or depressive symptoms: meta‐analysis of clinical trials

Background No study has gathered evidence from all randomized clinical trials ( RCT s) with anti‐inflammatory drugs measuring antidepressant effects including a detailed assessment of side‐effects and bias. Methods We performed a systematic review identifying RCT s 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 RCT s, whereof 13 investigated NSAID s ( N = 4214), 9 cytokine inhibitors ( N = 3345), seven statins ( N = 1576), 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; I 2 = 51%; N = 597) and as monotherapy ( SMD = −0.41; 95%‐ CI = −0.60, −0.22; I 2 = 93%, N = 8825). Anti‐inflammatory add‐on improved response ( RR = 1.76; 95%‐ CI = 1.44–2.16; I 2 = 16%; N = 341) and remission ( RR = 2.14; 95%‐ CI = 1.03–4.48; I 2 = 57%; N = 270). We found a trend toward an increased risk for infections, and all studies showed high risk of bias. Conclusion Anti‐inflammatory agents improved antidepressant treatment effects. Future RCT s need to include longer follow‐up, identify optimal doses and subgroups of patients that can benefit from anti‐inflammatory intervention.