THE FIRST TEST DOSE TO PREDICT LONGER-TERM TREATMENT RESPONSE IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD). Can we identify children and adults who may benefit from methylphenidate (MPH), the most common medication for ADHD, from their initial response to a single test dose rather than after several weeks of daily treatment?

Research question: Can the response to a single (test) dose of methylphenidate (MPH), the most used first-line medication for Attention-Deficit/Hyperactivity Disorder (ADHD), identify individuals who will benefit from MPH longer-term? Background: ADHD affects 5-7% of children, and its impairing symptoms persist in up to 75% of adults. Pharmacological treatment for ADHD is primarily managed by specialist mental health services and is among the most prescribed in psychiatry. Increasing demand has led to waiting times of up to 5 years or more. Identifying the most efficacious treatment for each individual may take months. MPH is usually given first, and response is assessed after several weeks of daily treatment. If not effective, patients may require sequential trials of different medications. This approach is time-consuming and costly for already overstretched services, and problematic because untreated ADHD is associated with educational and occupational failure, substance misuse, increased mortality, and life-time costs exceeding £100,000/person. Given the prevalence and often-lifelong debilitating course of ADHD, early access to effective treatment is crucial. This necessitates a paradigm shift towards evidence-based precision medicine approaches. MPH starts acting immediately. Experimental studies, including my own, suggested that brain functional changes detected from one hour after a single MPH dose predicted longer-term treatment response. However, neuroimaging is not available in routine mental health services due to high costs. During the fellowship, I will investigate whether single-dose effects predict longer-term response using low-cost measures that are feasible in clinical settings. Aims and objectives: to identify children/adults who can benefit from MPH (and those that need alternative medication) from their initial response to a single dose rather than after several weeks of treatment. Methods: this project includes three work packages (WPs): WP1) Single-dose study with 2-month follow-up: investigates whether clinically detectable changes under a single MPH dose predict clinical response at two months. Each of the 126 participants with ADHD will complete symptom scales, cognitive tasks, and simple physiological monitoring (e.g., heart rate) twice; once under a single MPH dose and once under placebo. After single-dose testing, they will start standard MPH treatment. I expect that an initial improvement under a single MPH dose will predict an improvement after two-month standard treatment. WP2) Naturalistic 6-month follow-up: investigates whether the initial response/non-response to a single MPH dose predicts clinical/service-use outcomes at 6 months (e.g., change in medication and drop-outs). WP3) Model development and selection: integrates stakeholder feedback to develop and select prediction models most suitable to be tested for potential clinical implementation, based on performance, clinical utility, and usability. Timeline: WP1-2 by year 3, WP3 by year 5. Anticipated impact and dissemination: considering current caseloads and waiting times, this research is timely and will support more personalised and cost-effective treatment approaches. Findings will be disseminated in high-impact scientific journals, national/international conferences, and meetings for the public. The same approach could be tested for other ADHD medications. This work will provide a solid foundation for further funding applications to evaluate this approach in clinical settings, and to potentially support its clinical implementation nationally and internationally.