Impact of drug holidays on simulated driving performance in adults with ADHD: a study protocol for a randomized crossover trial

Impact of drug holidays on simulated driving performance in adults with ADHD: a study protocol for a randomized crossover trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Impact of drug holidays on simulated driving performance in adults with ADHD: a study protocol for a randomized crossover trial Nan Li, Veronika Gambin, Boris Quednow, Pascal Burger, Ana Buadze, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8611309/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background Attention deficit hyperactivity disorder (ADHD) is linked to an increased risk of traffic accidents, primarily due to inattentiveness. Both stimulant and nonstimulant medications have proven effective in reducing ADHD symptoms, thereby supporting safe driving under well-managed treatment plans. In pediatric care, “drug holidays”, i.e. short-term interruptions in medication, are commonly used to mitigate side effects without compromising therapeutic efficacy. Drug holidays have been quickly adopted by adults and are increasingly recognized and accepted within therapeutic frameworks. Although stimulant treatment has been shown to enhance driving performance, no studies have yet directly investigated the effects of drug holidays on adult drivers. This study protocol aims to examine the impact of stimulant drug holidays on driving performance in adults with ADHD using a driving simulation. Methods This study presents a protocol for a monocentric, within-subjects, participant-randomized, observer-blinded crossover trial of a cohort of ADHD patients practicing drug holidays. Eligible participants are randomly assigned to either Group 1 (M-M-D) or Group 2 (M-D-M), completing a test sequence in different orders of medicated (M) and unmedicated (“drug holiday“, D) states to assess the effects of medication withdrawal on driving performance. The primary outcome is the Integrated Driving Score (IDS), calculated as a summation of Z-scores of key driving parameters during a 40-minute monotonous car-following task. Data will be analyzed using Linear Mixed Models (LMM). Secondary exploratory outcomes include physiological metrics from eye-tracking and electroencephalography (EEG), subjective psychometric assessments, and pharmacokinetic validation via medication levels in blood, saliva, urine, and exhaled breath. Discussion This study investigates the functional consequences of stimulant drug holidays on driving safety in adults with ADHD. While the findings are specific to the simulated context, they will potentially yield a novel evidence-based avenue to guide safety-related clinical decisions for patients considering or practicing drug holidays, potentially complementing future fitness-to-drive guidelines. Trial registration : ClinicalTrials.gov, NCT06910605. Registered 04 April 2025, https://clinicaltrials.gov/study/NCT06910605 ADHD Driving simulation Drug holiday Driving performance Stimulant treatment Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 20 Jan, 2026 Editor assigned by journal 19 Jan, 2026 Submission checks completed at journal 19 Jan, 2026 First submitted to journal 15 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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trial","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ADHD, Driving simulation, Drug holiday, Driving performance, Stimulant treatment","lastPublishedDoi":"10.21203/rs.3.rs-8611309/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8611309/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eAttention deficit hyperactivity disorder (ADHD) is linked to an increased risk of traffic accidents, primarily due to inattentiveness. Both stimulant and nonstimulant medications have proven effective in reducing ADHD symptoms, thereby supporting safe driving under well-managed treatment plans. In pediatric care, “drug holidays”, i.e. short-term interruptions in medication, are commonly used to mitigate side effects without compromising therapeutic efficacy. Drug holidays have been quickly adopted by adults and are increasingly recognized and accepted within therapeutic frameworks. Although stimulant treatment has been shown to enhance driving performance, no studies have yet directly investigated the effects of drug holidays on adult drivers. This study protocol aims to examine the impact of stimulant drug holidays on driving performance in adults with ADHD using a driving simulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eThis study presents a protocol for a monocentric, within-subjects, participant-randomized, observer-blinded crossover trial of a cohort of ADHD patients practicing drug holidays. Eligible participants are randomly assigned to either Group 1 (M-M-D) or Group 2 (M-D-M), completing a test sequence in different orders of medicated (M) and unmedicated (“drug holiday“, D) states to assess the effects of medication withdrawal on driving performance. The primary outcome is the Integrated Driving Score (IDS), calculated as a summation of Z-scores of key driving parameters during a 40-minute monotonous car-following task. Data will be analyzed using Linear Mixed Models (LMM). Secondary exploratory outcomes include physiological metrics from eye-tracking and electroencephalography (EEG), subjective psychometric assessments, and pharmacokinetic validation via medication levels in blood, saliva, urine, and exhaled breath.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion \u003c/strong\u003eThis study investigates the functional consequences of stimulant drug holidays on driving safety in adults with ADHD. While the findings are specific to the simulated context, they will potentially yield a novel evidence-based avenue to guide safety-related clinical decisions for patients considering or practicing drug holidays, potentially complementing future fitness-to-drive guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: ClinicalTrials.gov, NCT06910605. 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