Department of Psychiatry, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; and Mental Health Program, Amsterdam Public Health, Amsterdam, The Netherlands.
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Br J Psychiatry. 2024 Mar;224(3):89-97. doi: 10.1192/bjp.2023.148.
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.
To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.
Data on 2551 individuals with depression across the iSPOT-D ( = 967), CO-MED ( = 665), GENDEP ( = 773) and EMBARC ( = 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.
Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms ( = 376, β = 0.06, 0.049, 95% CI 0.0001-0.12, = 3.61%); this was also found for an IMD index combining these features ( = 372, β = 0.12, s.e. = 0.12, 0.031, 95% CI 0.01-0.22, 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 (β = 0.16) and the IMD index (β = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.
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.
根据“免疫代谢抑郁”（IMD）维度对患者进行分析，这种维度描述了一组与能量调节和免疫代谢失调相关的非典型抑郁症状，可能会优化个性化治疗。
检验假设，即基线 IMD 特征预测抗抑郁药治疗效果较差。
使用 iSPOT-D（n=967）、CO-MED（n=665）、GENDEP（n=773）和 EMBARC（n=146）临床试验中 2551 名抑郁症患者的数据。预测因子包括基线时非典型能量相关症状（AES）严重程度、体重指数（BMI）和 C 反应蛋白水平（CRP，仅在三项试验中），并分别聚合为 IMD 指数。对个体试验数据集进行主要结局（抑郁症状严重程度变化）的混合模型分析和次要结局（反应和缓解）的逻辑回归分析，并使用随机效应荟萃分析进行汇总。
尽管 AES 严重程度和 BMI 并未预测抑郁症状严重程度的变化，但较高的基线 CRP 预示着抑郁症状的减轻幅度较小（n=376，β=0.06，95%CI 0.0001-0.12，=3.61%）；对于结合这些特征的 IMD 指数（n=372，β=0.12，s.e.=0.12，95%CI 0.01-0.22，=23.91%）也发现了同样的结果，与 CRP 相比，其效应量虽然仍然较小，但仍然较大。将分析仅限于选择性 5-羟色胺再摄取抑制剂使用者，表明 CRP（β=0.16）和 IMD 指数（β=0.20）的影响更大。基线 IMD 特征无论是单独还是合并使用，都不能预测反应或缓解。
接受抗抑郁药治疗的 IMD 特征更多的患者，抑郁症状改善幅度较小。然而，由于关联不一致且效应量较小，临床相关性有限。这些患者是否会从针对免疫代谢途径的治疗中获益更多，仍有待研究。
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