Neuropsychiatric Disease and Treatment (Jan 2023)
Anti-Inflammatory Treatment Efficacy in Major Depressive Disorder: A Systematic Review of Meta-Analyses
Abstract
Maria S Simon,1,2 Gara Arteaga-Henríquez,3,4 Ahmed Fouad Algendy,1,5 Timo Siepmann,1,6 Ben MW Illigens1,7 1Division of Health Care Sciences, Dresden International University, Dresden, Saxony, Germany; 2Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University, Munich, Bavaria, Germany; 3Department of Psychiatry, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 4Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain; 5Clinical Pharmacy, Geriatric Department, Rumailah Hospital, Hamad Medical Corporation, Doha, Qatar; 6Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany; 7Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USACorrespondence: Maria S Simon, Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University Munich, Nußbaumstraße 7, Munich, 80336, Germany, Tel +4989440052769, Email [email protected]: Immune imbalances in major depressive disorder (MDD) have been targeted by anti-inflammatory treatment approaches in clinical trials to increase responsiveness to therapy. However, even after several meta-analyses, no translation of evidence into clinical practice has taken place. We performed a systematic review to evaluate meta-analytic evidence of randomized controlled trials on the use of anti-inflammatory agents for MDD to summarize efficacy estimates and elucidate shortcomings.Methods: Pooled effect estimates and heterogeneity indices were primary outcomes. Characteristics of the included meta-analyses were extracted. Scientific quality of meta-analyses was assessed using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR).Results: N=20 meta-analyses met the eligibility criteria. Study characteristics like outcome scales, composition of patient populations, and add-on or monotherapy regimen varied very little for celecoxib studies, varied little for minocycline studies, and were rather variable for omega 3 fatty acids studies. R-AMSTAR scores ranged from 26 to 39 out of 44 points indicating variable quality, where a comprehensive literature search was the strongest and the consideration of scientific quality in the conclusions was the weakest domain across all meta-analyses. For minocycline and celecoxib, superiority was demonstrated with medium to large effect size with substantial heterogeneity and with large to very large effect size with negligible heterogeneity, respectively. For omega 3 fatty acids, superiority was also demonstrated with mainly small and medium effect sizes with substantial heterogeneity. However, for minocycline and omega 3 fatty acids, non-significant meta-analyses were found also.Conclusion: Even in our synthesized approach, no clear recommendations could be derived on the use of anti-inflammatory treatment for MDD due to several critical aspects like heterogeneity, diversity of patient populations, treatment regimen, and outcomes, and limited scientific quality. However, we observed clear inter-substance differences with meta-analytic evidence being strongest for celecoxib and weakest for omega 3 fatty acids.Keywords: major depressive disorder, inflammation, anti-inflammatory therapy, state of knowledge, methodological shortcomings
