Department of Drug ResearchClinical Pharmacology, Faculty of Health Sciences, Linkping University, Department of Clinical Pharmacology, County Council of Linkping, Linkping, Sweden.
CNS Drugs. 2012 Aug 1;26(8):649-62. doi: 10.2165/11633920-000000000-00000.
Since chlorpromazine was introduced to the market in the early 1950s, the use of antipsychotic drugs has been associated with venous thromboembolism (VTE) in a number of reports. During the last decade the evidence has been strengthened with large epidemiological studies. Whether all antipsychotics increase the risk for VTE or the risk is confined to certain drugs is still unclear. The aim of this article is to present an updated critical review focusing on the incidence, mechanisms and management of VTE in users of antipsychotics. After searching the databases PubMed and Scopus for relevant articles we identified 12 observational studies, all of which were published after the year 2000. In most of these studies an elevated risk of VTE was observed for antipsychotic drugs, with the highest risk for clozapine, olanzapine and low-potency first-generation antipsychotics. The risk seems to be correlated with dose. The elderly, who mainly use lower doses, do not show an increased risk of VTE to the same extent as younger subjects. The underlying biological mechanisms explaining the association between antipsychotic medication and VTE are to a large extent unknown. Several hypotheses have been proposed, such as body weight gain, sedation, enhanced platelet aggregation, increased levels of antiphospholipid antibodies, hyperprolactinaemia and hyperhomocysteinaemia. The risk of VTE in schizophrenia and other psychotic disorders may also be related to the underlying disease rather than the medication. Very limited evidence exists to guide how cases of VTE in subjects using antipsychotics should be handled. An attempt to compile an algorithm where the patients' individual risk of VTE is assessed and preventive clinical measures are suggested has been published recently. Strong consideration should be given to discontinuation of the offending antipsychotic drug in patients experiencing a VTE, and another antipsychotic drug with a presumably lower risk should be chosen if antipsychotic drug treatment is still indicated. It is essential that physicians and patients are aware that VTE may be an adverse drug reaction to the antipsychotic treatment so the condition is identified early and treated appropriately.
自 20 世纪 50 年代氯丙嗪问世以来，多项报告显示抗精神病药物的使用与静脉血栓栓塞症（VTE）有关。在过去十年中，大量的流行病学研究进一步证实了这一点。目前尚不清楚是否所有抗精神病药物都会增加 VTE 的风险，还是风险仅限于某些特定药物。本文旨在对目前的文献进行更新，重点介绍抗精神病药物使用者 VTE 的发病机制、发生机制和管理。我们在 PubMed 和 Scopus 数据库中检索了相关文章，共确定了 12 项观察性研究，这些研究均发表于 2000 年以后。在这些研究中，大多数研究观察到抗精神病药物与 VTE 风险升高相关，氯氮平、奥氮平和低效能第一代抗精神病药物的风险最高。这种风险似乎与剂量相关。主要使用低剂量药物的老年人，其 VTE 风险增加程度不如年轻患者。目前尚不清楚解释抗精神病药物与 VTE 之间关联的潜在生物学机制。目前已经提出了几种假设，例如体重增加、镇静、血小板聚集增强、抗磷脂抗体水平升高、高催乳素血症和高同型半胱氨酸血症。精神分裂症和其他精神病性障碍患者 VTE 的风险也可能与基础疾病而非药物有关。目前，几乎没有证据可以指导使用抗精神病药物的患者出现 VTE 时应如何处理。最近发表了一种尝试性的算法，根据患者 VTE 的个体风险评估并提出预防临床措施。对于发生 VTE 的患者，应强烈考虑停用有问题的抗精神病药物，如果仍需要抗精神病药物治疗，则应选择风险较低的另一种抗精神病药物。医生和患者必须意识到 VTE 可能是抗精神病治疗的不良反应，以便及早识别并进行适当治疗。
