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ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases

  • Isabell Brikell
  • , Honghui Yao
  • , Lin Li
  • , Aske Astrup
  • , Le Gao
  • , Malcolm B. Gillies
  • , Tian Xie
  • , Yanli Zhang-James
  • , Søren Dalsgaard
  • , Anders Engeland
  • , Stephen V. Faraone
  • , Jan Haavik
  • , Catharina Hartman
  • , Patrick Ip
  • , Unnur Jakobsdóttir Smári
  • , Henrik Larsson
  • , Kenneth K.C. Man
  • , Juliana de Oliveira Costa
  • , Sallie Anne Pearson
  • , Nina Pil Hostrup Nielsen
  • Harold Snieder, Theresa Wimberley, Ian C.K. Wong, Le Zhang, Helga Zoega, Kari Klungsøyr, Zheng Chang*
*Corresponding author for this work
    • Universitetet i Bergen
    • Karolinska Institutet
    • Aarhus University
    • University of Hong Kong
    • University of New South Wales, Australia
    • University of Groningen, University Medical Center Groningen
    • Norton College of Medicine
    • Mental Health Services of the Capital Region
    • Københavns Universitet
    • Haukeland University Hospital
    • University of Iceland
    • Örebro University
    • University of London
    • University College London Hospitals NHS Foundation Trust
    • Laboratory of Data Discovery for Health
    • Norwegian Institute of Public Health

    Research output: Contribution to journalArticlepeer-review

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    Abstract

    Background: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice. Methods: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4–11 years], adolescents [age 12–17 years], young adults [age 18–24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available. Findings: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8–21 years) were included in the study. Across countries, treatment discontinuation 1–5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60–70) of children, 47% (43–51) of adolescents, 39% (36–42) of young adults, and 48% (44–52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50–60% of children and 30–40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex. Interpretation: Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use. Funding: European Union Horizon 2020 Research and Innovation Programme.

    Original languageEnglish
    Pages (from-to)16-26
    Number of pages11
    JournalThe Lancet Psychiatry
    Volume11
    Issue number1
    Early online date27 Nov 2023
    DOIs
    Publication statusPublished - Jan 2024

    Bibliographical note

    Copyright © 2024 Elsevier Ltd. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License [https://creativecommons.org/licenses/by-nc-nd/4.0/].

    Funding

    This study was funded by the European Union Horizon 2020 Research and Innovation Programme (grant 965381). This research reflects only the authors' view, and the European Commission is not responsible for any use that may be made of the information it contains. This study was additionally supported by the Swedish Research Council for Health, Working Life and Welfare (2022-01111); the Australian National Health and Medicine Research Council (NHMRC)–European Union Collaborative research grant (APP2007048); and Stiftelsen Kristian Gerhard Jebsen (SKGJ MED-02). We thank the Australian Government Services Australia for supplying the data, the NHMRC Centre of Research Excellence in Medicines Intelligence (ID: 1196900), and the University of New South Wales Scientia Program for providing support.

    FundersFunder number
    Australian National Health and Medicine Research Council
    NHMRC Centre of Research Excellence in Medicines Intelligence1196900
    University of New South Wales Scientia Program
    Stiftelsen Kristian Gerhard JebsenSKGJ MED-02
    European Commission
    National Health and Medical Research CouncilAPP2007048
    Forskningsrådet om Hälsa, Arbetsliv och Välfärd2022-01111
    Horizon 2020

    Keywords

    • Adolescent
    • Adult
    • Attention Deficit Disorder with Hyperactivity/drug therapy
    • Central Nervous System Stimulants/therapeutic use
    • Child
    • Child, Preschool
    • Female
    • Humans
    • Longevity
    • Male
    • Netherlands
    • Retrospective Studies
    • Young Adult

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