- Early drug treatment for ADHD in Sweden was tied to reduced risk of suicidal behavior, substance misuse, transport accidents, and crime.
- Benefits extended to recurrent events, possibly due to improved impulsivity, attention, and executive functioning, the researchers suggested.
- Findings persisted when treatment initiation was extended to 6 months of diagnosis and when drug switches were taken into account.
Drug treatment for attention deficit/hyperactivity disorder (ADHD) was tied to reduced risks for a handful of dangerous and harmful behaviors, a Swedish target trial emulation found.
The study evaluated 148,581 adults and children with ADHD. Compared with non-initiators, those who started drug treatment within 3 months of diagnosis had reduced rates of the first occurrence of four outcomes over 2 years:
- Suicidal behaviors: adjusted incidence rate ratio (aIRR) 0.83, 95% CI 0.78-0.88
- Substance misuse: aIRR 0.85, 95% CI 0.83-0.87
- Transport accidents: aIRR 0.88, 95% CI 0.82-0.94
- Criminality: aIRR 0.87, 95% CI 0.83-0.90
"These results provide evidence on the effects of ADHD drug treatment on important health-related and social outcomes that should inform clinical practice and the debate on the drug treatment of ADHD," wrote Zheng Chang, PhD, MSc, of the Karolinska Institutet in Stockholm, and colleagues in The BMJ.
"The beneficial effects of ADHD drug treatment observed in our study may be explained by reductions in impulsivity and improvements in attention and executive functions, in line with findings from randomised controlled trials," the researchers added.
"For instance, reduced impulsivity may lower criminality by curbing aggressive behavior, whereas enhanced attention may decrease the risk of transport accidents by minimizing distractions," they wrote.
ADHD drug initiators also had significantly lower rates for recurrent events of suicidal behaviors (aIRR 0.85, 95% CI 0.77-0.93), substance misuse (aIRR 0.75, 95% CI 0.72-0.78), transport accidents (aIRR 0.84, 95% CI 0.76-0.91), and criminality (aIRR 0.75, 95% CI 0.71-0.79).
To a smaller degree, these patients also had fewer recurrent accidental injuries (aIRR 0.96, 95% CI 0.92-0.99). While modest, the researchers said this reduction "remains clinically relevant."
Rate reductions may be more pronounced for recurrent events "because people with multiple occurrences of such events typically have more severe ADHD, making them more likely to benefit from drug treatment," Chang and co-authors observed.
Chang's group studied a nationwide sample of Swedish residents with ADHD. Participants were ages 6 to 64 years and had an incident ADHD diagnosis from January 2007 to December 2018. Criminality and transport accidents were assessed in a sub-cohort only of those 15 years and older, as 15 is the minimum legal age for criminal responsibility and driving in Sweden.
Mean age of the overall cohort was 17.4 years and 41.3% were female. More than half (56.7%) started drug treatment for ADHD, with methylphenidate most commonly prescribed at initiation.
Stimulant ADHD drugs were associated with lower event rates than non-stimulants, the researchers said. Subgroup analyses showed that rate reductions were more pronounced in people with a prior history of the events.
Rate reductions were greater in adults (ages 25 and older) compared with children and youth for first-time substance misuse (aIRR 0.83 vs 0.92, P<0.01) and criminality (aIRR 0.81 vs 0.90, P<0.01). Children and youth, but not adults, had a significantly lower rate for recurrent suicidal behaviors (aIRR 0.80, 95% CI 0.70-0.91).
Rate reductions were also more pronounced in women than men for first-time criminality (aIRR 0.81 vs 0.90, P<0.01).
Chang's group found similar outcomes to the main analysis in a sensitivity analysis that extended the initiation period to the first 6 months of ADHD diagnosis and allowed for switches between ADHD drugs during follow-up.
The researchers also applied a negative outcome control of type 1 diabetes to assess for potential biases and residual confounding and found, as expected, no link between developing type 1 diabetes and ADHD drug treatment. This suggested "that the risk of bias from unmeasured confounding (for example, greater health awareness, social engagement, and support) is unlikely to explain the associations between treatment and studied outcomes," Change and colleagues wrote.
Study limitations included a lack of data about drug adherence and an inability to assess the effect of ADHD drug dosage.
Findings may not be generalizable outside of Sweden, where 88.4% of ADHD drug initiators started with methylphenidate, the researchers acknowledged.
Disclosures
The study received support from the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council.
Chang reported speaker fees from Takeda Pharmaceuticals.
Co-authors reported relationships with the Swedish Research Council for Health, Working Life and Welfare, the Swedish Research Council, ìShizu Matsumuraîs Donation, KI Research Grants, the Swedish Heart-Lung Foundation, the Söderström König Foundation, Fredrik och Ingrid Thurings Stiftelse, the American Foundation for Suicide Prevention, the National Institute for Health and Care Research, the European Research Executive Agency, Shire Pharmaceuticals, Medici, Shire/Takeda Pharmaceuticals, Evolan Pharma AB, the Association for Child and Adolescent Mental Health, the Canadian ADHD Alliance Resource, the British Association of Psychopharmacology, the Healthcare Convention, CCM Group team, and the European ADHD Guidelines Group.
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