In a groundbreaking new study published in BMC Psychiatry, researchers have shed light on the complex factors dictating sertraline serum concentrations in both pediatric and adult populations. Sertraline, a commonly prescribed selective serotonin reuptake inhibitor (SSRI) used in treating depression and anxiety disorders, is notable for its highly variable serum levels across individuals. Understanding these variations is crucial for optimizing therapeutic outcomes, minimizing adverse effects, and personalizing treatment strategies.
The study involved an extensive retrospective analysis of therapeutic drug monitoring (TDM) data collected from 1,076 patients, encompassing 474 children and adolescents as well as 602 adults, over a six-year period from 2018 to 2024. Employing advanced statistical techniques, including multivariable generalized linear regression and restricted cubic spline modeling, investigators sought to elucidate the interplay between clinical and biochemical parameters with sertraline concentrations, emphasizing age-related differences.
One of the pivotal findings revealed that the daily prescribed dose and levels of aspartate aminotransferase (AST), an enzyme linked to liver function, were consistently and positively correlated with sertraline serum concentration across both age cohorts. This robust association indicates that hepatic metabolism plays a central role in determining sertraline availability, corroborating earlier evidence that hepatic enzymatic activity critically influences SSRI pharmacokinetics.
Intriguingly, the study highlighted a significant effect of sex on sertraline concentration, with females exhibiting notably higher serum levels compared to males. Specifically, girls and adolescent females had 43% higher sertraline levels than their male counterparts, while adult women demonstrated a 37% increase relative to men. This sex disparity underscores the necessity for sex-specific dosing considerations in clinical practice and suggests possible hormonal or metabolic mechanisms influencing drug disposition.
Further age-specific observations revealed that in children and adolescents, serum albumin and neutrophil counts significantly affected sertraline concentrations. Albumin, a principal plasma protein responsible for drug binding, may modulate free drug availability, while neutrophil count, a marker of immune status, could reflect underlying physiological or inflammatory states altering drug metabolism. These findings paint a nuanced picture of how developmental and immunological factors may shape therapeutic drug levels in younger patients.
Genetic polymorphisms of the cytochrome P450 2C19 enzyme (CYP2C19) were also explored due to their known influence on sertraline metabolism. Although patients classified as poor metabolizers (PMs) tended to have elevated sertraline concentrations, these differences did not reach statistical significance in adults. However, within the pediatric and adolescent subpopulation, dose-adjusted serum concentrations (C/D ratios) significantly varied across CYP2C19 genotypes, with PMs showing higher C/D values. This observation propels the conversation on personalized medicine, especially pharmacogenomics-guided dosing, to reduce the risk of toxicity or subtherapeutic exposure in vulnerable groups.
Adding another layer of complexity, the researchers examined the relationship between systemic inflammation and sertraline levels by assessing high-sensitivity C-reactive protein (hsCRP) in a subset of 593 patients. In children and adolescents, sertraline concentration exhibited a distinctive nonlinear, U-shaped correlation with hsCRP levels, suggesting that both low and high inflammatory states can unpredictably impact drug metabolism or distribution. This highlights an intriguing immunopharmacological interaction necessitating further mechanistic studies.
These multifaceted insights collectively emphasize the importance of monitoring a constellation of patient-specific variables—including dosage, liver function markers, sex, age, genetic phenotype, and inflammatory status—to inform sertraline dosing strategies. The findings advocate for enhanced therapeutic drug monitoring services that integrate clinical, biochemical, and genetic data to facilitate precision psychiatry.
Moreover, this research calls for clinicians to consider dynamic physiological changes, especially in pediatric populations undergoing developmental changes that may rapidly alter drug pharmacokinetics. Tailoring treatment to individual metabolic profiles ensures not only efficacy but also patient safety, particularly when prescribing psychotropic medications with narrow therapeutic indices.
The study’s retrospective design, while robust, also identifies areas ripe for prospective investigations, including longitudinal tracking of sertraline metabolism in relation to evolving clinical parameters and external factors such as concomitant medications or comorbidities. The observed U-shaped relationship between inflammation and sertraline levels presents a novel avenue to explore, potentially linking immune dysfunction with psychiatric pharmacotherapy.
By advancing the understanding of sertraline pharmacokinetics through a comprehensive, age-stratified analysis, this work represents a crucial leap towards more personalized, effective antidepressant therapy. It underscores the emergent paradigm shift in psychopharmacology where one-size-fits-all prescribing is increasingly supplanted by precision medicine, guided by robust patient-specific biomarkers.
As the psychiatric field continues to grapple with treatment resistance and adverse drug reactions, this study offers actionable insights to optimize SSRI use. The prospect of combining TDM with pharmacogenomics and inflammatory profiling foreshadows a future where mental health treatment is as tailored as possible, maximizing benefits while minimizing harms across diverse patient groups.
In an era of increasing mental health challenges globally, such refined approaches to medication management are essential. This research paves the way for more nuanced clinical guidelines and underscores the vital role of interdisciplinary collaboration among psychiatrists, pharmacologists, geneticists, and laboratory specialists.
Future investigations should expand on these findings by integrating real-world data from diverse populations and leveraging novel analytical methods like machine learning to predict individual responses. Ultimately, a deeper mechanistic understanding of how biological variables influence psychotropic drug behavior will revolutionize therapeutic drug monitoring and enhance clinical outcomes.
For now, the study serves as a clarion call to clinicians and researchers to embrace complexity in antidepressant pharmacotherapy and harness the full potential of personalized medicine in psychiatry.
Subject of Research: Factors influencing sertraline serum concentrations in children, adolescents, and adults using therapeutic drug monitoring data.
Article Title: Identifying factors related to sertraline concentrations in child/adolescent and adult patients: insights from a therapeutic drug monitoring service
Article References:
Li, R., Bi, B., Dong, Z. et al. Identifying factors related to sertraline concentrations in child/adolescent and adult patients: insights from a therapeutic drug monitoring service. BMC Psychiatry 25, 590 (2025). https://doi.org/10.1186/s12888-025-07033-6
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