title: The relation between dosage, serum concentrations, and clinical outcome in children and adolescents treated with sertraline:  a naturalistic study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. taurines@kjp.uni-wuerzburg.de
authors: Regina
authors: R
authors: Taurines
authors: Rainer
authors: R
authors: Burger
authors: Christoph
authors: C
authors: Wewetzer
authors: Bruno
authors: B
authors: Pfuhlmann
authors: Claudia
authors: C
authors: Mehler-Wex
authors: Manfred
authors: M
authors: Gerlach
authors: Karin
authors: K
authors: Egberts
mesh_terms: D000293:Adolescent; D002648:Child; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D020280:Sertraline / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline