Increased antipsychotic sensitivity in elderly patients: evidence and mechanisms.
Increased antipsychotic sensitivity in elderly patients: evidence and mechanisms.
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DOI：
10.4088/jcp.08r04171
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
H. Uchida;D. Mamo;B. Mulsant;B. Pollock;S. Kapur
中科院分区：
文献类型：
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作者：
H. Uchida;D. Mamo;B. Mulsant;B. Pollock;S. Kapur
目的：本文的主要目的是回顾文献抗精神病药物在老年人的临床效果，药代动力学和药效学，并检查潜在的机制与年龄相关的抗精神病药物敏感性。资料来源：通过检索PubMed（1950-2007）和相关文献及书籍中的参考文献确定本综述的资料。检索词包括抗精神病药、抗精神病药、老年人、衰老、药代动力学、药效学和多巴胺，仅查阅英文或日文文章。资料选择选择与老年患者使用抗精神病药的临床效果、药代动力学和药效学相关的研究、综述和书籍。资料综合流行的做法和临床指南表明，老年患者可以获得治疗的好处，在一个较低的剂量和经验，从抗精神病药物的不良反应往往比年轻的患者，虽然仍然有很少的试验，直接比较老年患者与年轻。文献表明，药物的脑通路与年龄相关，并证明多巴胺能系统中的主要成分（包括内源性多巴胺水平和多巴胺受体密度）随年龄增加而减少。结论：虽然临床医生最终认为，随着年龄的增长，患者对抗精神病药物变得更加敏感，但这一主张只有适度的经验支持，需要进一步调查。多巴胺能系统中的多巴胺相关功能下降预示老年患者抗精神病药物剂量较低。我们提出了一系列可检验的假设，以解决年龄相关的药代动力学和药效学变化对抗精神病药物敏感性的相对贡献。
OBJECTIVE The primary objective of this article is to review the literature regarding clinical effects, pharmacokinetics, and pharmacodynamics of antipsychotics in older people and to examine potential mechanisms underlying the age-related antipsychotic sensitivity. DATA SOURCES Data for this review were identified by searches of PubMed (1950-2007) and references from relevant articles and books. Search terms included antipsychotic, neuroleptic, elderly, aging, pharmacokinetics, pharmacodynamics, and dopamine, and only articles written in English or Japanese were consulted. DATA SELECTION Studies, reviews, and books pertaining to the clinical effects, pharmacokinetics, and pharmacodynamics with regard to the use of antipsychotics in older patients were selected. DATA SYNTHESIS The prevailing practices and clinical guidelines suggest that elderly patients can obtain therapeutic benefits at a lower dose and experience adverse effects from antipsychotics more often than younger patients, although there are still few trials that have directly compared elderly patients with the young. The literature suggests an age-related increase in brain access of drugs and demonstrates a decrease with age in the principal components in the dopaminergic system, including endogenous dopamine level and dopamine receptor density. CONCLUSIONS While clinicians conclusively hold that patients become more sensitive to antipsychotics as they become older, this proposition has only modest empirical support and warrants further investigation. Age-related functional decline in the dopaminergic system predicts lower antipsychotic doses for older patients. We propose a hierarchical series of testable hypotheses to address the relative contribution of age-related pharmacokinetic and pharmacodynamic changes to antipsychotic drug sensitivity.