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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., Competing Interests: Declaration of interests SF reports personal fees, travel expenses, and research grants from Johnson & Johnson, Aardvark, Aardwolf, Tris, Otsuka, Ironshore, KemPharm/Corium, Akili, Supernus, Atentiv, Noven, Sky Therapeutics, Axsome, and Genomind; has a US patent (via his institution) for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD (US20130217707 A1); receives royalties from books published by Guilford Press (Straight Talk about Your Child's Mental Health), Oxford University Press (Schizophrenia: The Facts), and Elsevier (ADHD: Non-Pharmacologic Interventions); and is program director of www.ADHDEvidence.org and www.ADHDinAdults.com. JH reports honoraria as part of continuing medical education programmes sponsored by Shire, Takeda, Medice and Biocodex, all outside the submitted work. HL reports grants from Shire Pharmaceuticals; personal fees and speaker fees from Medice, Shire/Takeda Pharmaceuticals, and Evolan Pharma AB; and sponsorship for a conference on ADHD from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work; and is Editor-in-Chief of JCPP Advances. KKCM reports grants from the C W Maplethorpe Fellowship, the National Institute for Health and Care Research, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council; and personal fees from IQVIA, all outside the submitted work. IW reports research grants outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, Glaxo Smith Kline, Novartis, Takeda, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund, UK National Institute for Health Research, European Commission, and Australian National Health and Medical Research Council; and is a non-executive director of Jacobson Medical in Hong Kong and a consultant to WHO. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)