Exploring the Association between Monoclonal Antibodies and Depression and Suicidal Ideation and Behavior: A VigiBase Study
Exploring the Association between Monoclonal Antibodies and Depression and Suicidal Ideation and Behavior: A VigiBase Study
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DOI：
10.1007/s40264-018-00789-9
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发表时间：
2019-07-01
期刊：
影响因子：
4.2
通讯作者：
Gardarsdottir, Helga
中科院分区：
文献类型：
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作者：
Minnema, Lotte A.;Giezen, Thijs J.;Gardarsdottir, Helga
前言几种单抗与患者的神经精神不良反应有关，包括抑郁和自杀意念和行为。目的本研究的目的是量化和表征与单抗使用者相关的抑郁症和自杀意念及行为的自发报道的药物不良反应(ADRs)，并探讨其可能的作用机制。方法收集VigiBase中报道的单抗ADRs，并鉴定与抑郁和自杀意念及行为相关的ADRs。根据它们对免疫系统的影响(不是直接针对[参考]、刺激或抑制)，估计每个单抗(以贝伐单抗为参考)的报告优势比(ROR)。结果44株单抗共纳入2924319个ADR，其中9455个ADR与抑郁有关，1770个ADR与自杀意念和行为有关。与抑郁症(ROR5.7，95%可信区间[CI]5.0-6.4；ROR5.1，95%CI 4.2-6.2)和自杀意念和行为(ROR12.0，95%CI 7.9-18.3；以及ROR20.2，95%CI 12.4-33.0)的相关性最强的是那他珠单抗和贝利单抗。那些抑制免疫系统的人表现出更高的ROR，抑郁症为1.9(95%CI 1.8~2.0)，自杀意念和行为为3.6(95%CI 3.0~4.4)。这一发现仅见于用于治疗自身免疫性疾病的单抗。结论使用单抗的患者存在抑郁和自杀意念和行为，特别是用于治疗抑制免疫系统的自身免疫性疾病的单抗。对于这些数据的解释，需要进一步考虑使用的适应症和其他特征。
Introduction Several monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse effects in patients, including depression and suicidal ideation and behavior.Objective The aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action.Methods We included mAb ADRs that were reported in VigiBase, and identified those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their influence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer).Results Overall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confidence interval [CI] 5.0-6.4; and ROR 5.1, 95% CI 4.2-6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9-18.3; and ROR 20.2, 95% CI 12.4-33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8-2.0) for depression and 3.6 (95% CI 3.0-4.4) for suicidal ideation and behavior. This finding was only seen for mAbs used for treating autoimmune diseases.Conclusion Depression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration.