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

<jats:sec><jats:title>Background</jats:title><jats:p>No study has gathered evidence from all randomized clinical trials (<jats:styled-content style="fixed-case">RCT</jats:styled-content>s) with anti‐inflammatory drugs measuring antidepressant effects including a detailed assessment of side‐effects and bias.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a systematic review identifying <jats:styled-content style="fixed-case">RCT</jats:styled-content>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 (<jats:styled-content style="fixed-case">MDD</jats:styled-content>) or depressive symptoms. Outcomes were depression scores after treatment, remission, response, and side‐effects. Pooled standard mean differences (<jats:styled-content style="fixed-case">SMD</jats:styled-content>) and risk ratios (<jats:styled-content style="fixed-case">RR</jats:styled-content>) including 95% confidence intervals (95%‐<jats:styled-content style="fixed-case">CI</jats:styled-content>) were calculated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified 36 <jats:styled-content style="fixed-case">RCT</jats:styled-content>s, whereof 13 investigated <jats:styled-content style="fixed-case">NSAID</jats:styled-content>s (<jats:italic>N </jats:italic>= 4214), 9 cytokine inhibitors (<jats:italic>N </jats:italic>= 3345), seven statins (<jats:italic>N </jats:italic>= 1576), 3 minocycline (<jats:italic>N </jats:italic>= 151), 2 pioglitazone (<jats:italic>N </jats:italic>= 77), and 2 glucocorticoids (N = 59). Anti‐inflammatory agents improved depressive symptoms compared to placebo as add‐on in patients with <jats:styled-content style="fixed-case">MDD</jats:styled-content> (<jats:styled-content style="fixed-case">SMD</jats:styled-content> = −0.64; 95%‐<jats:styled-content style="fixed-case">CI</jats:styled-content> = −0.88, −0.40; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 51%; <jats:italic>N </jats:italic>= 597) and as monotherapy (<jats:styled-content style="fixed-case">SMD</jats:styled-content> = −0.41; 95%‐<jats:styled-content style="fixed-case">CI</jats:styled-content> = −0.60, −0.22; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 93%, <jats:italic>N </jats:italic>= 8825). Anti‐inflammatory add‐on improved response (<jats:styled-content style="fixed-case">RR</jats:styled-content> = 1.76; 95%‐<jats:styled-content style="fixed-case">CI</jats:styled-content> = 1.44–2.16; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 16%; <jats:italic>N </jats:italic>= 341) and remission (<jats:styled-content style="fixed-case">RR</jats:styled-content> = 2.14; 95%‐<jats:styled-content style="fixed-case">CI</jats:styled-content> = 1.03–4.48; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 57%; <jats:italic>N </jats:italic>= 270). We found a trend toward an increased risk for infections, and all studies showed high risk of bias.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Anti‐inflammatory agents improved antidepressant treatment effects. Future <jats:styled-content style="fixed-case">RCT</jats:styled-content>s need to include longer follow‐up, identify optimal doses and subgroups of patients that can benefit from anti‐inflammatory intervention.</jats:p></jats:sec>