Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis
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- Li Tong
- Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University
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- Hu Kai
- Department of Neurology, Xiangya Hospital, Central South University National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University Clinical Research Center for Epileptic disease of Hunan Province, Central South University
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- Ye Ling
- Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University
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- Ma Junlong
- Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University
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- Huang Longjian
- Youjiang Medical University for Nationalities
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- Guo Chengjun
- School of Applied Mathematics, Guangdong University of Technology
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- Huang Xin
- Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University
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- Jiang Jie
- Department of Pediatrics, The Affiliated Changsha Central Hospital, University of South China Hengyang Medical School, University of South China
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- Xie Xiaoxue
- Department of Radiotherapy, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University
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- Guo Chengxian
- Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University
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- He Qingnan
- Department of Pediatrics, The Third Xiangya Hospital, Central South University
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<p> Aims: Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms.</p><p>Methods: We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes.</p><p>Results: In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action.</p><p>Conclusions: Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.</p>
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ
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Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ 31 (4), 396-418, 2024-04-01
一般社団法人 日本動脈硬化学会
