Efficacy of Anti-Inflammatory Treatment on Major Depressive Disorder or Depressive Symptoms: Meta-Analysis of Clinical Trials

Acta Psychiatr Scand. 2019 May;139(5):404-419. doi: 10.1111/acps.13016. Epub 2019 Mar 28.

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.

Keywords: NSAIDs; anti-inflammatory treatment; cytokine inhibitors; depression; depressive symptoms; glucocorticoids; inflammation; major depressive disorder; minocycline; personalized medicine; pioglitazone; psychoneuroimmunology; statins.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Cytokines / antagonists & inhibitors
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Glucocorticoids / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Male
  • Middle Aged
  • Minocycline / pharmacology
  • Odds Ratio
  • Outcome Assessment, Health Care
  • Pioglitazone / pharmacology
  • Placebos / administration & dosage
  • Randomized Controlled Trials as Topic
  • Remission Induction
  • Serotonin Uptake Inhibitors / therapeutic use
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Antidepressive Agents
  • Cytokines
  • Glucocorticoids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypoglycemic Agents
  • Placebos
  • Serotonin Uptake Inhibitors
  • Minocycline
  • Pioglitazone