Mario Negri Institute for Pharmacological Research, Department of Molecular Biochemistry and Pharmacology, Milan, Italy.
Expert Opin Drug Metab Toxicol. 2011 May;7(5):591-608. doi: 10.1517/17425255.2011.562198. Epub 2011 Mar 15.
There is an increasing use of antipsychotic drugs, particularly those of second- and third-generation, for a wide range of behavioral and affective disorders in pediatric and psychiatric practice. Limited data are available, however, regarding their safety and effectiveness, although children may be more vulnerable than adults to antipsychotic adverse effects because of developmental physiological changes that may affect their pharmacodynamic and pharmacokinetic profiles.
This review covers the antipsychotics now specifically approved in major markets for children as well as those that are used in these patients for unapproved or off-label indications taking into account the potential differences in drug disposition and metabolism among children, adolescents and adults. MEDLINE and EMBASE international databases were searched for studies concerning the pharmacokinetics, efficacy and safety of first-, second- ('atypical') and third-generation antipsychotic agents.
Few studies have systematically monitored the safety of antipsychotics in young populations. Data concerning long-term side effects are especially limited, and a systematic benefit-risk evaluation is needed. When prescribing antipsychotics, physicians should, therefore, monitor patients closely for metabolic adverse events, hyperprolactinemia, extrapyramidal symptoms and corrected QT prolongation. Dose selection should include a careful consideration of the drugs' pharmacokinetic profiles and, when these are lacking therapeutic drug monitoring should be implemented as it is often a valid tool to optimize pediatric psychiatric practice.
在儿科和精神科实践中，越来越多地将抗精神病药物（尤其是第二代和第三代）用于广泛的行为和情感障碍。然而，关于它们的安全性和有效性的数据有限，尽管儿童可能比成年人更容易受到抗精神病药物不良反应的影响，因为发育中的生理变化可能会影响他们的药效学和药代动力学特征。
本文综述了目前在主要市场上专门批准用于儿童的抗精神病药物，以及这些药物在未经批准或超适应证用于这些患者时的情况，同时考虑了儿童、青少年和成人之间药物处置和代谢的潜在差异。检索了国际 MEDLINE 和 EMBASE 数据库中关于第一代、第二代（“非典型”）和第三代抗精神病药物药代动力学、疗效和安全性的研究。
很少有研究系统地监测抗精神病药物在年轻人群中的安全性。关于长期副作用的数据尤其有限，需要进行系统的获益-风险评估。因此，医生在开抗精神病药物时，应密切监测患者的代谢不良反应、高催乳素血症、锥体外系症状和校正 QT 延长。剂量选择应包括仔细考虑药物的药代动力学特征，如果缺乏这些特征，应实施治疗药物监测，因为它通常是优化儿科精神科实践的有效工具。
