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

Abstract

Objective: To examine the effects of drug treatment for attention deficit/hyperactivity disorder (ADHD) on suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality.

Design: Emulation of target trials.

Setting: Linkage of national registers in Sweden, 2007-20.

Participants: People aged 6-64 years with a new diagnosis of ADHD, who either started or did not start drug treatment for ADHD within three months of diagnosis.

Main outcome measures: First and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality.

Results: Of 148 581 individuals with ADHD (median age 17.4 years; 41.3% female), 84 282 (56.7%) started drug treatment for ADHD, with methylphenidate being the most commonly prescribed at initiation (74 515; 88.4%). Drug treatment for ADHD was associated with reduced rates of the first occurrence of suicidal behaviours (weighted incidence rates 14.5 per 1000 person years in the initiation group versus 16.9 in the non-initiation group; adjusted incidence rate ratio 0.83, 95% confidence interval 0.78 to 0.88), substance misuse (58.7 v 69.1 per 1000 person years; 0.85, 0.83 to 0.87), transport accidents (24.0 v 27.5 per 1000 person years; 0.88, 0.82 to 0.94), and criminality (65.1 v 76.1 per 1000 person years; 0.87, 0.83 to 0.90), whereas the reduction was not statistically significant for accidental injuries (88.5 v 90.1 per 1000 person years; incidence rate ratio 0.98, 0.96 to 1.01). The reduced rates were more pronounced among individuals with previous events, with incidence rate ratios ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. For recurrent events, drug treatment for ADHD was significantly associated with reduced rates of all five outcomes, with incidence rate ratios 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.

Conclusions: Drug treatment for ADHD 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 for 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.

Fig 1

Selection of study population. ADHD=attention deficit/hyperactivity disorder

Fig 2

Cumulative incidence of first occurrence of outcomes over two years of follow-up: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality, all stratified by attention deficit/hyperactivity disorder drug treatment strategy. Numbers reported are weighted and account for follow-up censoring, including treatment discontinuation or switching

Fig 3

Attention deficit/hyperactivity disorder (ADHD) drug treatment and rates of first and recurrent outcome events over two years of follow-up among people with ADHD. Incidence rates were calculated per 1000 person years. Numbers reported are weighted and account for follow-up censoring, including treatment discontinuation or switching. CI=confidence interval

Fig 4

Incidence rates of recurrent events of outcomes over two years of follow-up. Incidence rates were calculated per 1000 person years. Numbers reported are weighted and account for follow-up censoring, including treatment discontinuation or switching

Fig 5

Attention deficit/hyperactivity disorder (ADHD) drug treatment and rates of first outcome event over two years of follow-up among individuals with ADHD, by history of events. Incidence rates were calculated per 1000 person years. Numbers reported are weighted and account for follow-up censoring, including treatment discontinuation or switching. Wald test for differences between incidence rate ratios for individuals without history versus those with history of events across five outcomes (suicidal behaviours, substance misuse, unintentional injuries, transport accidents, and criminality) yielded P values of 0.14, <0.01, 0.22, 0.40, and 0.02, respectively. CI=confidence interval

Fig 6

Sensitivity analyses of attention deficit/hyperactivity disorder drug treatment and rates of first outcome event over two years of follow-up. Incidence rates were calculated per 1000 person years. Numbers reported are weighted and account for follow-up censoring. CI=confidence interval