de Leon Jose, Diaz Francisco J
University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, KY 40508, USA.
Schizophr Res. 2007 Nov;96(1-3):185-97. doi: 10.1016/j.schres.2007.05.020. Epub 2007 Jul 6.
The variability of individual responses reported by the CATIE study has raised awareness of the need to reconsider personalizing prescriptions of antipsychotic medications for the purpose of establishing the best antipsychotic for each individual patient. As atypical antipsychotics are widely prescribed for severe mental illnesses other than schizophrenia and side effects are largely independent from diagnosis, personalizing antipsychotic dosing may have important public health implications. This hypothesis article emphasizes that, whereas other psychiatric medications may cause weight gain, antipsychotics appear to have additional effects. Antipsychotics may have direct effects (not explained by obesity) on hypertension, diabetes mellitus and hyperlipidemia. The clinical and pharmacoepidemiological literature appears to suggest that (1) antipsychotics rarely increase blood pressure, with the probable exception of clozapine; (2) antipsychotics (particularly clozapine and olanzapine) may interfere with glucose metabolism in a (still unknown) direct way, independently of their effects on obesity; and (3) clozapine and olanzapine (and possibly quetiapine and low-potency typical antipsychotics) may directly cause hyperlipidemia, independently of their effects on obesity. This commentary focuses on the effect sizes and the time interval/event sequence of the direct influences of antipsychotics on blood pressure, glucose metabolism and lipid metabolism. Cross-sectional lipid studies may show antipsychotic effects. It is hypothesized that it may be easier to design studies focusing on these three aspects than to design pharmacogenetic studies focusing on antipsychotic-induced weight gain or metabolic syndrome, which require long-term follow-up.
CATIE研究报告的个体反应变异性，提高了人们对于重新考虑抗精神病药物处方个性化必要性的认识，目的是为每位患者确定最佳的抗精神病药物。由于非典型抗精神病药物被广泛用于治疗精神分裂症以外的严重精神疾病，且副作用在很大程度上与诊断无关，因此抗精神病药物剂量的个性化可能具有重要的公共卫生意义。这篇假说文章强调，虽然其他精神科药物可能导致体重增加，但抗精神病药物似乎有额外的影响。抗精神病药物可能对高血压、糖尿病和高脂血症有直接影响（并非由肥胖所致）。临床和药物流行病学文献似乎表明：（1）抗精神病药物很少升高血压，氯氮平可能是个例外；（2）抗精神病药物（尤其是氯氮平和奥氮平）可能以一种（尚不清楚的）直接方式干扰葡萄糖代谢，独立于其对肥胖的影响；（3）氯氮平和奥氮平（可能还有喹硫平和低效价典型抗精神病药物）可能直接导致高脂血症，独立于其对肥胖的影响。这篇评论聚焦于抗精神病药物对血压、葡萄糖代谢和脂质代谢的直接影响的效应大小以及时间间隔/事件顺序。横断面脂质研究可能显示抗精神病药物的作用。据推测，设计关注这三个方面的研究可能比设计关注抗精神病药物引起的体重增加或代谢综合征的药物遗传学研究更容易，后者需要长期随访。
