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Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study

Published online by Cambridge University Press:  20 February 2023

Chungsoo Kim
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
Dong Yun Lee
Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea
Jimyung Park
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
Su-Jin Yang
Gwangju Smile Center for Crime victim support, Gwangju, South Korea
Eng Hooi Tan
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Centre of Statistics in Medicines, University of Oxford, Oxford, UK
Daniel Prieto-Alhambra
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Centre of Statistics in Medicines, University of Oxford, Oxford, UK Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
Yo Han Lee
Department of Preventive Medicine and Public Health, Ajou University School of Medicine, Suwon, South Korea
Sangha Lee
Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea
Seong-Ju Kim
Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea
Jeewon Lee
Department of Psychiatry, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
Rae Woong Park
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea
Yunmi Shin*
Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea
Author for correspondence: Yunmi Shin, E-mail:



Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation.


We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings.


The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25–0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups.


The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

Original Article
Copyright © The Author(s), 2023. Published by Cambridge University Press

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Those authors contributed equally as co-first author.

Those authors contributed equally as co-senior author.

This article has been updated since its original publication. A notice detailing the updates can be found here:


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