Flanagan Robert J, Dunk Louisa
Toxicology Unit, Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK.
Hum Psychopharmacol. 2008 Jan;23 Suppl 1:27-41. doi: 10.1002/hup.917.
Almost all classes of psychotropic agents have been reported to cause blood dyscrasias. Mechanisms include direct toxic effects upon the bone marrow, the formation of antibodies against haematopoietic precursors or involve peripheral destruction of cells. Agranulocytosis is probably the most important drug-related blood dyscrasia. The mortality from drug-induced agranulocytosis is 5-10% in Western countries. The manifestations of agranulocytosis are secondary to infection. Aggressive treatment with intravenous broad-spectrum antimicrobials and bone marrow stimulants may be required. Of drugs encountered in psychiatry, antipsychotics including clozapine (risk of agranulocytosis approximately 0.8%, predominantly in the first year of treatment) and phenothiazines (chlorpromazine agranulocytosis risk approximately 0.13%), and antiepileptics (notably carbamazepine, neutropenia risk approximately 0.5%) are the most common causes of drug-related neutropenia/agranulocytosis. Drugs known to cause neutropenia should not be used concomitantly with other drugs known to cause this problem. High temperature and other indicators of possible infection should be looked for routinely during treatment. Clozapine is well known as a drug that can cause blood dyscrasias, but olanzapine and other atypicals may also cause similar problems. In addition to genetic factors, there are likely to be dose-related and immunological components to these phenomena. Important lessons have been learnt from the haematological monitoring that is necessary with clozapine and the monitoring has been very successful in preventing deaths related to clozapine-induced agranulocytosis. Continuing research into the mechanisms of drug-induced neutropenia and agranulocytosis may serve to further enhance the safe use not only of clozapine, but also of other agents.
几乎所有种类的精神药物都有导致血液系统疾病的报道。其机制包括对骨髓的直接毒性作用、针对造血前体细胞形成抗体或涉及细胞的外周破坏。粒细胞缺乏症可能是最重要的药物相关性血液系统疾病。在西方国家，药物性粒细胞缺乏症的死亡率为5% - 10%。粒细胞缺乏症的表现继发于感染。可能需要积极使用静脉注射广谱抗菌药物和骨髓刺激剂进行治疗。在精神科使用的药物中，抗精神病药物包括氯氮平（粒细胞缺乏症风险约为0.8%，主要在治疗的第一年）和吩噻嗪类药物（氯丙嗪粒细胞缺乏症风险约为0.13%），以及抗癫痫药物（尤其是卡马西平，中性粒细胞减少风险约为0.5%）是药物相关性中性粒细胞减少/粒细胞缺乏症最常见的原因。已知会导致中性粒细胞减少的药物不应与其他已知会引起此问题的药物同时使用。治疗期间应常规检查是否有高热及其他可能感染的指标。氯氮平是一种众所周知的可导致血液系统疾病的药物，但奥氮平和其他非典型抗精神病药物也可能引起类似问题。除了遗传因素外，这些现象可能还存在剂量相关和免疫方面的因素。从氯氮平所需的血液学监测中吸取了重要经验教训，这种监测在预防氯氮平所致粒细胞缺乏症相关死亡方面非常成功。对药物性中性粒细胞减少和粒细胞缺乏症机制的持续研究可能不仅有助于进一步提高氯氮平的安全使用，也有助于提高其他药物的安全使用。
