In an expansive and revealing nationwide study conducted in South Korea, researchers have shed new light on the real-world clinical application and persistence of selective serotonin reuptake inhibitors (SSRIs) in managing depression among children and adolescents. This comprehensive investigation, which meticulously analyzed data from the Health Insurance Review and Assessment Service spanning over a decade, unravels the nuanced patterns of treatment continuity and modification associated with the three most commonly prescribed SSRIs: fluoxetine, escitalopram, and sertraline. The insights gleaned from this population-based retrospective cohort study carry profound implications for pediatric psychiatric care, underscoring the complexity and individualization demanded in the pharmacological management of young patients grappling with depression.
Depression during childhood and adolescence presents unique challenges to clinical treatment, not least because of the delicate neurodevelopmental processes ongoing at these ages. SSRIs are frequently prescribed as first-line pharmacotherapy due to their efficacy in modulating serotonergic pathways implicated in mood regulation. Despite their widespread use, there has been a significant gap in understanding long-term treatment persistence and the specific patterns through which therapies are modified in real-world settings. The current study offers a granular examination of these dynamics, covering patients aged 5 to 19 years who initiated treatment with one of the three SSRIs between 2009 and 2018.
One of the most striking findings of this investigation is that less than 3% of pediatric patients remained on their initial SSRI regimen after one year of treatment. This low rate of persistence markedly highlights the fluid and often unstable nature of pharmacological treatment strategies in young populations. The majority of patients underwent treatment changes, which were predominantly characterized by simple discontinuation. This trend calls attention to the challenges clinicians face in maintaining therapeutic adherence and the potential impact on treatment outcomes.
Beyond discontinuation, the study delineates other modification patterns, including switching between SSRIs, combining antidepressants, and augmentation with antipsychotic medications. Such therapeutic strategies are typically employed in clinical practice when initial treatments prove insufficient or elicit intolerable side effects. The differential rates and risks associated with each SSRI to these modifications unveil important subtleties in their clinical utility and tolerability profiles.
Fluoxetine emerged as the SSRI with the lowest risk for treatment modifications, notably in the domains of combination and augmentation strategies. This finding might reflect fluoxetine’s relatively favorable efficacy and side effect spectrum, which could confer a clinical advantage in sustaining monotherapy. Conversely, escitalopram demonstrated the lowest switching rates, suggesting a potential steadiness in patient acceptance or physician preference for this agent when initial choice fails to suffice without needing to altogether discontinue.
Interestingly, sertraline was associated with the lowest risk of simple discontinuation, indicating enhanced tolerance or better symptom control which facilitates sustained use. These distinctions are critical, given that each SSRI has a unique pharmacodynamic and pharmacokinetic profile, influencing not only efficacy but also side effect burden, adherence patterns, and the likelihood of treatment optimization. Understanding these nuances equips clinicians with evidence-based parameters to tailor pharmacotherapy more precisely for each patient.
The complex interplay of sociodemographic and clinical variables further emerged as a significant determinant of treatment patterns. Psychiatric comorbidities, a common feature among youth with depression, were notably influential, underscoring the necessity for holistic assessment beyond isolated symptoms or diagnoses. Such factors compound the challenges of pharmacotherapy, necessitating regular monitoring and dynamic treatment adjustments to accommodate evolving clinical needs.
This study’s methodology—leveraging a nationwide, population-based database—adds robustness and generalizability to these findings. It transcends the limitations intrinsic to clinical trial settings, providing a panoramic view of SSRI usage in routine clinical practice. By systematically applying Cox proportional hazards modeling to estimate adjusted hazard ratios, the researchers were able to quantify differences in risk associated with each SSRI while controlling for confounding variables, thereby enhancing the rigor of their conclusions.
Equally noteworthy is the study’s emphasis on individualized SSRI selection. While pharmacological profiles offer indispensable guidance, incorporating patient-specific characteristics, including comorbid conditions and sociodemographic context, remains essential to optimize treatment outcomes. The absence of a single SSRI agent that consistently outperforms others in all respects reflects the heterogeneous nature of pediatric depression and the necessity for personalized therapeutic strategies.
The clinical implications extend beyond pharmacological selection. They underscore the importance of ongoing assessment and flexibility in treatment approach, recognizing that early therapy modifications—whether discontinuation, switching, or augmentation—may often signal unmet clinical needs rather than mere patient non-compliance. This insight encourages proactive management rather than reactive adjustments.
Moreover, these findings may inform clinical guidelines and health policy, emphasizing the allocation of resources toward support structures that foster adherence, such as psychoeducation, caregiver involvement, and integrated mental health services. Such strategies could mitigate premature treatment discontinuation and improve long-term outcomes in this vulnerable population.
The intricate patterns revealed in this study also beckon further research into the biological and psychosocial determinants of treatment response variability among children and adolescents. Future investigations might explore genetic markers, pharmacogenomics, and environmental interactions that influence SSRI tolerability and efficacy, paving the way toward precision psychiatry.
In sum, this landmark study from South Korea advances our understanding of pediatric antidepressant treatment dynamics on a national scale. The differential persistence and modification patterns among fluoxetine, escitalopram, and sertraline highlight the multifaceted considerations intrinsic to managing pediatric depression pharmacologically. The findings advocate for a nuanced, individualized approach that integrates both drug-specific characteristics and patient-centric factors to optimize therapeutic efficacy and durability.
As the global mental health community continues to grapple with the growing burden of depression among youth, such population-based evidence serves as a critical compass guiding clinical practice toward more effective and sustainable treatment paradigms. This work not only elucidates current real-world treatment landscapes but also charts a pathway for future innovations in pediatric psychopharmacology.
Subject of Research: Treatment persistence and modification patterns of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents with depression in South Korea.
Article Title: Treatment persistence and modification patterns of SSRIs in children and adolescents with depression: a nationwide population-based study in South Korea.
Article References:
Lee, D.Y., Cha, S., Kwon, JW. et al. Treatment persistence and modification patterns of SSRIs in children and adolescents with depression: a nationwide population-based study in South Korea. BMC Psychiatry 25, 1091 (2025). https://doi.org/10.1186/s12888-025-07521-9
Image Credits: AI Generated
DOI: 17 November 2025
