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Category: Project

Description: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by inappropriate levels of inattentiveness, hyperactivity, and impulsivity. Diagnosed typically in childhood but often persisting into adulthood, ADHD affects approximately 5% of children and 2.5% of adults globally (1). Beyond its core symptoms, ADHD is associated with significant adverse functional outcomes, including increased risks of suicidal behaviors, substance misuse, accidental injuries, transport accidents and criminality (2). While pharmacological therapy is the recommended first-line treatment and has proven effective in alleviating core symptoms in numerous randomized controlled trials (RCTs) (3), these trials are often limited by their controlled environments and short follow-up periods, which may not capture the diverse population of individuals with ADHD or study rare but significant functional outcomes (4). Observational studies suggest that ADHD medications may reduce the risks of suicidal behaviors, substance misuse, accidental injuries, transport accidents and criminality (5, 6), but these studies are susceptible to confounding factors that can introduce bias. To address these limitations, the proposed study will use data from linkage of Swedish registers and a target trial emulation approach. This method mimics the design of an RCT using observational data, explicitly defining eligibility criteria, treatment strategies, follow-up periods, and outcome measures (7). This study aims to provide more reliable estimates of the causal effects of ADHD medications on real-world outcomes, including suicidal behaviors, substance misuse, accidental injuries, transport accidents and criminality. We will also examine the rates of both first and recurrent events to examine the impacts of ADHD medications on these outcomes. Additionally, we will evaluate the effects of ADHD medications among individuals with and without prior histories of these outcomes, acknowledging the potential differences in their risk profiles. References: 1. Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. American Journal of Psychiatry, 164(6), 942-948. 2. Faraone, S. V., Buitelaar, J., & Ramos-Quiroga, J. A. (2015). The world federation of ADHD international consensus statement: 208 evidence-based conclusions about the disorder. European Neuropsychopharmacology, 25(5), 734-746. 3. Cortese, S., Adamo, N., Del Giovane, C., Mohr-Jensen, C., Hayes, A. J., Carucci, S., ... & Cipriani, A. (2018). Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry, 5(9), 727-738. 4. Schachter, H. M., Pham, B., King, J., Langford, S., & Moher, D. (2001). How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CMAJ, 165(11), 1475-1488. 5. Chang, Z., Lichtenstein, P., D'Onofrio, B. M., Almqvist, C., Kuja-Halkola, R., Sjölander, A., & Larsson, H. (2014). Maternal age at childbirth and risk for ADHD in offspring: a population-based cohort study. International Journal of Epidemiology, 43(6), 1815-1824. 6. Dalsgaard, S., Østergaard, S. D., Leckman, J. F., Mortensen, P. B., & Pedersen, M. G. (2015). Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. The Lancet, 385(9983), 2190-2196. 7. Hernán, M. A., & Robins, J. M. (2016). Using big data to emulate a target trial when a randomized trial is not available. American Journal of Epidemiology, 183(8), 758-764.