South London & Maudsley NHS Foundation Trust, London, UK.
Pharmacogenomics. 2013 Nov;14(15):1907-14. doi: 10.2217/pgs.13.182.
Clozapine is a uniquely efficacious antipsychotic drug in treatment-resistant schizophrenia. Its use is restricted due to adverse effects including a rare but dangerous reduction in neutrophils (agranulocytosis) and the mandatory hematological monitoring this entails in many countries. We review the statistical, ethical and legal issues arising from a hypothetical pharmacogenetic test for clozapine, using the UK as an exemplary case for consideration. Our key findings include: a consideration of the probabilistic results that a pharmacogenetic test may return; the impact on drug licensing; and the potential for pharmacogenetic tests for clozapine being used without consent under the UK's legal framework. We make recommendations regarding regulatory changes applicable to the special case of pharmacogenetic testing in clozapine treatment.
氯氮平是一种在治疗抵抗性精神分裂症中具有独特疗效的抗精神病药物。由于其副作用，包括罕见但危险的中性粒细胞减少（粒细胞缺乏症），以及许多国家都需要进行强制性血液学监测，其使用受到限制。我们以英国为例，综述了氯氮平假设的药物遗传学检测所引发的统计学、伦理和法律问题。我们的主要发现包括：考虑药物遗传学检测可能返回的概率结果；对药物许可的影响；以及在英国法律框架下，未经同意使用氯氮平药物遗传学检测的可能性。我们就适用于氯氮平治疗中药物遗传学检测这一特殊情况的监管变化提出了建议。
