Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Ther Drug Monit. 2013 Feb;35(1):84-91. doi: 10.1097/FTD.0b013e31827a1aad.
This naturalistic therapeutic drug monitoring (TDM) study aimed to evaluate the relationship between dosage, serum concentration, and clinical outcome in children and adolescents treated with the serotonin reuptake inhibitor sertraline for different indications.
Steady-state trough serum concentrations were analyzed in 90 subjects, treated with 25-200 mg sertraline per day. Therapeutic efficacy was assessed by the Clinical Global Impression Improvement subscale and side effects by the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale.
In the study population, children were administered higher body weight normalized daily doses than adolescents. The relationships between sertraline daily dosage and serum concentrations (rs = 0.67, P < 0.0001) as well as between body weight normalized daily doses and serum concentrations (r = 0.62, P < 0.0001) were linear. In the whole patient group, no correlation between serum concentrations and either the therapeutic effect or side effects could be observed, neither significant effects of gender, age, concomitant medications, or smoking habits. When analyzing just the patients with depression, those with side effects had significantly higher sertraline serum concentrations than those without (44.8 ng/mL versus 22.3 ng/mL, P = 0.01). In general, occurrence of side effects was significantly more frequent in patients with psychiatric comedication (37.9%) than those without (11.5%, P = 0.002).
As this study has the typical limitations of naturalistic studies, the results should be interpreted cautiously. From the data, it is not possible to suggest an age-specific therapeutic window for children and adolescents. However, as the intraindividual variability of sertraline serum concentrations is known to be low, TDM may certainly help to predict serum concentrations after dose adjustment, to assess pharmacokinetic drug-drug interactions influencing serum concentrations and the patient's compliance, finally allowing for personalizing dose through TDM.
本项自然疗法药物监测（TDM）研究旨在评估不同适应证儿童和青少年接受 SSRIs 类药物舍曲林治疗时，剂量、血清浓度与临床疗效之间的关系。
共分析了 90 例接受舍曲林 25-200mg/天治疗的患者的稳态谷浓度。采用临床总体印象改善量表评估治疗效果，采用 Udvalg for Kliniske Undersogelser-Side Effect Rating Scale 量表评估不良反应。
在研究人群中，儿童的体质量校正日剂量高于青少年。舍曲林日剂量与血清浓度（rs=0.67，P＜0.0001）以及体质量校正日剂量与血清浓度（r=0.62，P＜0.0001）之间均呈线性关系。在整个患者组中，未观察到血清浓度与治疗效果或不良反应之间存在相关性，也未观察到性别、年龄、合并用药或吸烟习惯存在显著影响。仅对抑郁症患者进行分析时，有不良反应患者的血清浓度显著高于无不良反应患者（44.8ng/ml 比 22.3ng/ml，P=0.01）。一般而言，有精神科合并用药的患者发生不良反应的频率显著高于无合并用药的患者（37.9%比 11.5%，P=0.002）。
由于本研究具有自然研究的典型局限性，因此应谨慎解释研究结果。从数据来看，无法为儿童和青少年确定特定年龄的治疗窗。然而，由于已知舍曲林血清浓度的个体内变异性较低，TDM 可帮助预测剂量调整后的血清浓度，评估影响血清浓度和患者依从性的药代动力学药物相互作用，最终通过 TDM 实现剂量个体化。
