O Köhler-Forsberg1,2,3, C N Lydholm3, C Hjorthøj3,4,5, M Nordentoft3,4, O Mors1,2,4, M E Benros3,4. 1. Psychosis Research Unit, Aarhus University Hospital Psychiatry, Aarhus, Denmark. 2. Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. 3. Copenhagen Research Center for Mental Health -CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. 4. iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. 5. Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen.
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 = 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; I2 = 51%; N = 597) and as monotherapy (SMD = -0.41; 95%-CI = -0.60, -0.22; I2 = 93%, N = 8825). 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 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.
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 = 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; I2 = 51%; N = 597) and as monotherapy (SMD = -0.41; 95%-CI = -0.60, -0.22; I2 = 93%, N = 8825). 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 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.
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