Efficacy of anti‐inflammatory treatment on major depressive disorder or depressive symptoms: meta‐analysis of clinical trials
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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; 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 RCT s need to include longer follow‐up, identify optimal doses and subgroups of patients that can benefit from anti‐inflammatory intervention.
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- Authors
- Köhler‐Forsberg, O., N. Lydholm, C., Hjorthøj, C., Nordentoft, M., Mors, O., & Benros, M. E.
- Affiliations
- Aarhus University Hospital (DK)
- Copenhagen Research Center for Mental Health ‐CORE Mental Health Center Copenhagen Copenhagen University Hospital Copenhagen Denmark
- University of Copenhagen (DK)
- Copenhagen University Hospital (DK)
- Corresponding author
- Köhler‐Forsberg, O.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2019-03-28
- Volume
- 139
- Issue
- 5
- Pages
- 404-419
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2919938711
- Semantic Scholar
- d265538579a0e54af55c740a539e49f5be103f6e
- Cited by
- 432
- References
- 66
- Citations by year
- 2026: 42 · 2025: 59 · 2024: 73 · 2023: 63 · 2022: 61 · 2021: 74 · 2020: 40 · 2019: 20
- FWCI
- 30.10
- Type
- journal article
- Language
- en
- Open access
- green
- pure.au.dk
- Licence
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Lundbeckfonden (R268-2016–3925, R248‐2017‐2003, R278–2018-1411)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- anti-inflammatory agents, major depressive disorder, depressive symptoms, antidepressant efficacy, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, minocycline, pioglitazone, glucocorticoids, remission, treatment response, adverse effects, infection risk, risk of bias
- MeSH terms
- Pioglitazone, Adolescent, Adult, Aged, Anti-Inflammatory Agents, Anti-Bacterial Agents, Antidepressive Agents, Major Depressive Disorder, Female, Glucocorticoids, Humans, Hypoglycemic Agents, Male, Middle Aged, Minocycline, Placebos, Remission Induction, Odds Ratio, Randomized Controlled Trials as Topic, Cytokines, Outcome Assessment, Health Care, Selective Serotonin Reuptake Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Young Adult
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