Aldrich Stacey L, Poweleit Ethan A, Prows Cynthia A, Martin Lisa J, Strawn Jeffrey R, Ramsey Laura B
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Front Pharmacol. 2019 Feb 19;10:99. doi: 10.3389/fphar.2019.00099. eCollection 2019.
In pediatric patients, the selective serotonin reuptake inhibitors (SSRIs) escitalopram and citalopram (es/citalopram) are commonly prescribed for anxiety and depressive disorders. However, pharmacogenetic studies examining CYP2C19 metabolizer status and es/citalopram treatment outcomes have largely focused on adults. We report a retrospective study of electronic medical record data from 263 youth < 19 years of age with anxiety and/or depressive disorders prescribed escitalopram or citalopram who underwent routine clinical genotyping. Slower CYP2C19 metabolizers experienced more untoward effects than faster metabolizers ( 0.015), including activation symptoms ( = 0.029) and had more rapid weight gain ( = 0.018). A larger proportion of slower metabolizers discontinued treatment with es/citalopram than normal metabolizers ( = 0.007). Meanwhile, faster metabolizers responded more quickly to es/citalopram ( = 0.005) and trended toward less time spent in subsequent hospitalizations ( = 0.06). These results highlight a disparity in treatment outcomes with es/citalopram treatment in youth with anxiety and/or depressive disorders when standardized dosing strategies were used without consideration of CYP2C19 metabolizer status. Larger, prospective trials are warranted to assess whether tailored dosing of es/citalopram based on CYP2C19 metabolizer status improves treatment outcomes in this patient population.
在儿科患者中,选择性5-羟色胺再摄取抑制剂(SSRI)艾司西酞普兰和西酞普兰(艾司/西酞普兰)常用于治疗焦虑症和抑郁症。然而,关于CYP2C19代谢状态与艾司/西酞普兰治疗效果的药物遗传学研究主要集中在成年人。我们报告了一项回顾性研究,该研究基于263名19岁以下患有焦虑症和/或抑郁症且正在接受艾司西酞普兰或西酞普兰治疗的青少年的电子病历数据,这些青少年均接受了常规临床基因分型。与代谢较快者相比,CYP2C19代谢较慢者出现更多不良反应(P = 0.015),包括激越症状(P = 0.029),且体重增加更快(P = 0.018)。与正常代谢者相比,代谢较慢者停用艾司/西酞普兰治疗的比例更高(P = 0.007)。同时,代谢较快者对艾司/西酞普兰的反应更快(P = 0.005),且后续住院时间有缩短趋势(P = 0.06)。这些结果突显了在未考虑CYP2C19代谢状态而采用标准化给药策略时,艾司/西酞普兰治疗青少年焦虑症和/或抑郁症的治疗效果存在差异。有必要开展更大规模的前瞻性试验,以评估根据CYP2C19代谢状态调整艾司/西酞普兰剂量是否能改善该患者群体的治疗效果。