Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials K€ ohler-Forsberg O, Nicolaisen Lydholm C, Hjorthøj C, Nordentoft C, Mors O, Benros ME. 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 (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 sideeffects 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 = 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 = À0.64; 95%-CI = À0.88, À0.40; I 2 = 51%; N = 597) and as monotherapy (SMD = À0.41; 95%-CI = À0.60, À0.22; I 2 = 93%, N = 8825). Antiinflammatory 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 RCTs need to include longer follow-up, identify optimal doses and subgroups of patients that can benefit from anti-inflammatory intervention.
Summations• Among 36 RCTs including almost 10 000 patients, five out of six anti-inflammatory drugs improved depression scores compared to placebo.• Short-term (i.e., weeks) anti-inflammatory add-on to antidepressants showed improved antidepressant effects in MDD without increasing the risk for side-effects.• The effect size for anti-inflammatory add-on to antidepressants was similar to the effect size of antidepressants alone, indicating the potential clinical benefit.
Considerations• Few studies reported on side-effects and all studies were associated with risk of bias.• Few studies investigated biomarkers and none explored specific depressive symptoms to predict better response to anti-inflammatory treatment.• Hence, future studies need to include longer follow-up and measures of inflammation (blood, CSF, and brain scans) to identify subgroups of patients with specific depressive symptoms who could be offered anti-inflammatory treatment.
