Østmarka Psychiatric Department, St. Olav University Hospital, Trondheim, Norway.
Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
Acta Psychiatr Scand. 2017 Nov;136(5):455-464. doi: 10.1111/acps.12794. Epub 2017 Sep 2.
To investigate serum concentrations of second-generation antipsychotics in relation to age and gender in a population ranging from 18 to 100 years.
Results from a routine therapeutic drug monitoring database were retrieved, and 43 079 samples from 11 968 patients were included (17 249 samples for clozapine, 16 171 samples for olanzapine, 5343 samples for risperidone, and 4316 samples for quetiapine). The dose-adjusted concentration was used as the primary target variable. A linear mixed model was used to allow the inclusion of multiple samples from each patient.
Age had a significant impact on the concentrations of all four drugs. At the age of 80, the dose-adjusted concentrations were up to twice those of the age of 40. At the age of 90, dose-adjusted concentrations were two- to three-fold higher. Age-related increases were largest for clozapine (+108% at 80 years; +197% at 90 years) and smallest for olanzapine (+28% at 80 years; +106% at 90 years). Females generally had dose-adjusted concentrations 20-30% higher than males.
The effect of age on the serum concentrations of the antipsychotics studied becomes pronounced with advanced age. The patient population aged above 70 should be subdivided according to exact age, and considerable dose reductions are recommended.
调查 18 至 100 岁人群中二、三代抗精神病药的血清浓度与年龄和性别的关系。
从常规治疗药物监测数据库中检索结果，纳入 11968 例患者的 43079 份样本（氯氮平 17249 份，奥氮平 16171 份，利培酮 5343 份，喹硫平 4316 份）。使用剂量调整后的浓度作为主要目标变量。采用线性混合模型允许每个患者包含多个样本。
年龄对所有四种药物的浓度均有显著影响。80 岁时，药物调整后的浓度是 40 岁时的两倍。90 岁时，剂量调整后的浓度增加了两倍至三倍。年龄相关性增加最大的是氯氮平（80 岁时增加 108%；90 岁时增加 197%），奥氮平最小（80 岁时增加 28%；90 岁时增加 106%）。女性的药物调整后浓度通常比男性高 20-30%。
随着年龄的增长，研究中抗精神病药的血清浓度受年龄的影响变得明显。年龄在 70 岁以上的患者人群应根据确切年龄进一步细分，并建议大幅减少剂量。
