TY - JOUR
T1 - Features of immunometabolic depression as predictors of antidepressant treatment outcomes
T2 - pooled analysis of four clinical trials
AU - Vreijling, Sarah R
AU - Chin Fatt, Cherise R
AU - Williams, Leanne M
AU - Schatzberg, Alan F
AU - Usherwood, Tim
AU - Nemeroff, Charles B
AU - Rush, A John
AU - Uher, Rudolf
AU - Aitchison, Katherine J
AU - Köhler-Forsberg, Ole
AU - Rietschel, Marcella
AU - Trivedi, Madhukar H
AU - Jha, Manish K
AU - Penninx, Brenda W J H
AU - Beekman, Aartjan T F
AU - Jansen, Rick
AU - Lamers, Femke
N1 - Funding Information: Funding for this work was provided by ZonMw (The Netherlands Organization for Health Research and Development), research programme GGZ (project number: 636310017). The EMBARC study was supported by NIMH grants U01MH092221 (to M.H.T.) and U01MH092250 (to Drs McGrath, Parsey and Weissman). The CO-MED trial was funded by National Institute of Mental Health under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (Principal Investigators, M.H.T. and A.J.R.). The GENDEP trial was funded by a European Commission Framework 6 grant, LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge. GlaxoSmithKline and the Medical Research Council (UK) contributed by funding add-on projects in the London centre. The iSPOT-D trial was sponsored by Brain Resource Company Operations Pty Ltd. Publisher Copyright: © The Author(s), 2023. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
PY - 2023/12/22
Y1 - 2023/12/22
N2 - BACKGROUND: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.AIMS: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.METHOD: Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses.RESULTS: Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, βpooled = 0.06, P = 0.049, 95% CI 0.0001-0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, βpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01-0.22, I2= 23.91%), with a higher - but still small - effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (βpooled = 0.16) and the IMD index (βpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.CONCLUSIONS: Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.
AB - BACKGROUND: Profiling patients on a proposed 'immunometabolic depression' (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.AIMS: To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.METHOD: Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses.RESULTS: Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, βpooled = 0.06, P = 0.049, 95% CI 0.0001-0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, βpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01-0.22, I2= 23.91%), with a higher - but still small - effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (βpooled = 0.16) and the IMD index (βpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.CONCLUSIONS: Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.
KW - Antidepressants
KW - depressive disorders
KW - inflammation
KW - profiling
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85181445808&partnerID=8YFLogxK
U2 - https://doi.org/10.1192/bjp.2023.148
DO - https://doi.org/10.1192/bjp.2023.148
M3 - Article
C2 - 38130122
SN - 0007-1250
SP - 1
EP - 9
JO - The British journal of psychiatry : the journal of mental science
JF - The British journal of psychiatry : the journal of mental science
ER -