Institute of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
Basic Clin Pharmacol Toxicol. 2024 Oct;135(4):523-533. doi: 10.1111/bcpt.14074. Epub 2024 Sep 1.
Over the past decade, increasing off-label use of quetiapine has been reported worldwide from various sources. We wanted to investigate how this is reflected in therapeutic drug monitoring (TDM) data. Requisitions for serum concentration measurements of quetiapine from a TDM service in Central Norway during 2001-2019 were obtained and analysed for age, gender, trends in quetiapine doses, serum concentrations and indicators of diagnoses. There were 19 759 requisitions from 7459 individuals. Daily doses of quetiapine decreased by 24 mg per year (95% CI: -25.61 to -21.48, p < 0.001, N = 4505). A corresponding decrease in quetiapine serum concentrations was not seen. The proportion of requisitions with diagnoses indicating reimbursable use was 13% for the whole study period. Mean daily doses were slightly higher in the reimbursable group, but declined over time in these samples, as well. To our understanding, these results signal a trend towards lower prescribed doses of quetiapine, possibly reflecting drug repurposing and/or off-label use. The discrepancy in the decrease of doses versus serum concentrations may reflect the intake of higher doses than prescribed and/or inappropriate TDM sampling. Our findings show that TDM data have limitations when it comes to making inferences about the use of quetiapine based on serum concentrations and clinical information on the requisitions.
在过去的十年中，来自不同来源的全球范围内都有越来越多的喹硫平被报告为超适应证使用。我们希望调查这在治疗药物监测（TDM）数据中是如何反映的。我们获取了 2001 年至 2019 年期间挪威中部 TDM 服务中心的喹硫平血清浓度检测申请，并对年龄、性别、喹硫平剂量、血清浓度和诊断指标的趋势进行了分析。共有 7459 名患者的 19759 份申请。喹硫平的日剂量每年减少 24 毫克（95%CI：-25.61 至-21.48，p<0.001，N=4505）。但并未观察到喹硫平血清浓度相应降低。有诊断表明可报销使用的申请比例在整个研究期间为 13%。在可报销组中，平均日剂量略高，但在这些样本中也随时间下降。据我们了解，这些结果表明喹硫平的处方剂量呈下降趋势，这可能反映了药物重新定位和/或超适应证使用。剂量下降与血清浓度下降之间的差异可能反映了摄入的剂量高于规定剂量和/或 TDM 采样不当。我们的研究结果表明，TDM 数据在基于血清浓度和申请中的临床信息推断喹硫平的使用情况方面存在局限性。
