Antidepressant treatment effects and side effects of anti-inflammatory agents: A systematic review and meta-analysis of randomized clinical trials
Publikation: Bidrag til tidsskrift › Konferenceabstrakt i tidsskrift › Forskning › fagfællebedømt
Background: Specific anti-inflammatory agents may yield antidepressant effects; however, no study has gathered the evidence on all anti-inflammatory drugs including a detailed assessment of side effects and risk of bias. Objectives: To systematically review all randomized clinical trials (RCTs) that studied antidepressive treatment and side effects of pharmacological antiinflammatory intervention. Methods: We searched CENTRAL, PubMed, EMBASE, Psychinfo, Clinicaltrials.gov, and review articles for trials published prior to January 1, 2018. We included RCTs investigating anti-inflammatory intervention in adults with depressive symptoms or major depressive disorder (MDD). Two independent reviewers extracted data. Pooled standard mean differences (SMD) including 95%-confidence intervals (95%-CI) were calculated. Outcomes included depression scores after treatment including remission and response and side effects. Results: A total of 41 RCTs (N=10,344) were included, whereof 13 investigated NSAIDs (N=4,362), 11 cytokine-inhibitors (N=3,533), 9 statins (N=2,118), 3 minocycline (N=158), 3 pioglitazone (N=114), and 2 glucocorticoids (N=59). Overall, anti-inflammatory agents improved antidepressant treatment effects compared to placebo by a SMD of-0.46 (95%-CI=-0.62 to-0.30; I2=89%; N=9,459), which was present as add-on in patients with MDD (SMD=-0.56; 95%-CI=-0.84 to-0.27; I2=66%; N=634) and as monotherapy against depressive symptoms (SMD=-0.41; 95%-CI=-0.60 to-0.22; I2=93%, N=8,825). Better antidepressant effects were observed for NSAIDs as add-on (SMD=-0.82; 95%-CI=-1.17 to-0.46; I2=0%; N=132) and monotherapy (SMD=-0.29; 95%-CI=-0.51 to-0.06; I2=84%; N=4,082), cytokineinhibitors as monotherapy (SMD=-0.65; 95%-CI=-1.04 to-0.26; I2=95%; N=3,285), statins as add-on (SMD=-0.73; 95%-CI=-1.05 to-0.42; I2=0%; N=164), minocycline as monotherapy (SMD=-1.06; 95%-CI=-1.68 to-0.44; N=46), and glucocorticoids as add-on (SMD=-0.90; 95%-CI=-1.44 to-0.36; I2=0%; N=59). All studies were associated with high risk of bias. Only 19 trials reported on adverse events, and we found no increased risks for pain/muscle aching, gastrointestinal or cardiovascular events but a trend towards an increased risk for infections. Conclusion: The majority of anti-inflammatory agents improved antidepressant treatment effects. Future large, high-quality RCTs need to include longer follow-up, identify optimal doses and subgroups of patients that can benefit from anti-inflammatory intervention, possibly guided by neurovegetative symptoms, somatic comorbidity and pro-inflammatory markers.
Originalsprog | Engelsk |
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Tidsskrift | Acta Neuropsychiatrica |
Vol/bind | 30 |
Udgave nummer | S1 |
Sider (fra-til) | 14-15 |
Antal sider | 2 |
ISSN | 0924-2708 |
DOI | |
Status | Udgivet - 2018 |
- Antidepressive Agents, Embase, Medline, PsycINFO, adult, adverse drug reaction, antidepressant activity, antidepressant agent, cardiovascular disease, comorbidity, conference abstract, controlled study, cytokine, drug therapy, endogenous compound, female, follow up, gastrointestinal tract, glucocorticoid, human, hydroxymethylglutaryl coenzyme A reductase inhibit, infection, major depression, male, meta analysis, minocycline, monotherapy, muscle, nonsteroid antiinflammatory agent, pain, placebo, randomized controlled trial (topic), remission, side effect, systematic review
Forskningsområder
ID: 247180605