Ther Drug Monit. 2025 Sep 26. doi: 10.1097/FTD.0000000000001379. Online ahead of print.
ABSTRACT
BACKGROUND: Selective serotonin reuptake inhibitors, including escitalopram, sertraline, and fluoxetine, are frequently prescribed to treat depression and anxiety and obsessive-compulsive disorders in pediatric populations. These medications are associated with potential cardiac side effects, particularly corrected QT (QTc) interval prolongation. This study is the first to evaluate the association between serum concentrations of escitalopram, sertraline, and fluoxetine and QTc interval duration in children and adolescents.
METHODS: This retrospective naturalistic study included 431 patients treated with escitalopram, sertraline, or fluoxetine at the Department of Child and Adolescent Psychiatry, University Hospital, Würzburg, between 2016 and 2019, for whom therapeutic drug monitoring was performed. Serum concentrations of parent compounds, active metabolites, and active moieties were correlated with QTc intervals calculated using Bazett and Fridericia correction formulae.
RESULTS: A total of 287 patients were included in the study (escitalopram, n = 38; sertraline, n = 119; fluoxetine, n = 130). QTc prolongation (>450 ms) was observed in 5.3% of escitalopram, 4.2% of sertraline, and 5.4% of fluoxetine users. A positive correlation was found between QTc duration and serum concentrations of norfluoxetine, the active metabolite of fluoxetine (Bazett: r = 0.18, P = 0.02; Fridericia: r = 0.13, P = 0.07). No statistical association was identified between QTc interval and serum concentration of escitalopram or sertraline. Severe cardiac adverse events, such as Torsade de Pointes or arrhythmias, were not documented.
CONCLUSIONS: These findings suggest a positive correlation between norfluoxetine serum levels and QTc interval duration in children and adolescents. Monitoring norfluoxetine concentration may support individual dose adjustments to minimize the risk of QTc prolongation. However, confirmation in a larger cohort is required before clinical recommendations can be made.
PMID:41004670 | DOI:10.1097/FTD.0000000000001379
