ADHD pharmacotherapy and risk of suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality: emulation of target trials

Objective: to examine the effects of ADHD medication on five outcomes including suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. <br/><br/>Design: target trial emulations using cloning, censoring and weighting.<br/><br/>Setting: linkage of national registers in Sweden, 2007-2020.<br/><br/>Participants: individuals aged 6 to 64 years with a new diagnosis of ADHD, who either initiated or did not initiate ADHD medication within three months of diagnosis.<br/><br/>Main outcome measures: following consultation with individuals with lived experience, we assessed first and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. <br/><br/>Results: of 148 581 individuals with ADHD (median age, 17.4 years; 41.3% women), 84 282 (56.7%) individuals initiated ADHD medication, with methylphenidate being the most commonly prescribed at initiation (88.5%). The use of ADHD medication was associated with reduced rates in the first occurrence of suicidal behaviours (weighted incidence rates: 14.5 per 1 000 person-years in the initiation group vs. 16.9 in the non-initiation group; adjusted incidence rate ratio [IRR], 0.83, 95% confidence interval, 0.78 to 0.88), substance misuse (58.7 vs. 69.1 per 1 000 person-years; IRR, 0.85 [0.83 to 0.87]), transport accidents (24.0 vs. 27.5 per 1 000 person-years; IRR, 0.88 [0.82 to 0.94]), and criminality (65.1 vs. 76.1 per 1 000 person-years; IRR, 0.87 [0.83 to 0.90]), whereas the reduction was not statistically significant for accidental injuries (88.5 vs. 90.1 per 1 000 person-years; IRR, 0.98 [0.96 to 1.01]). The reduced rates were more pronounced among individuals with prior events, with IRR ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. When considering recurrent events, ADHD medication was significantly associated with reduced rates of all five outcomes, with IRR of 0.85 (0.77 to 0.93) for suicidal behaviours, 0.75 (0.72 to 0.78) for substance misuse, 0.96 (0.92 to 0.99) for accidental injuries, 0.84 (0.76 to 0.91) for transport accidents, and 0.75 (0.71 to 0.79) for criminality. <br/><br/>Conclusions: use of ADHD medication was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality, but not accidental injuries when considering first event rate. The risk reductions were more pronounced considering recurrent events, with reduced rates for all five outcomes. This target trial emulation study using national register data provides evidence that is representative of patients in routine clinical settings. <br/>