ADHD medication lowers risk of substance misuse and accidents

A study using Swedish national data shows that ADHD medications, especially stimulants, not only ease core symptoms but are also associated with lower risks of dangerous outcomes like suicide attempts, substance misuse, accidents, and crime.

Study: ADHD drug treatment and risk of suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality: emulation of target trials. Image credit: Motortion Films/Shutterstock.com

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition. Its adverse effect on normal functioning is well established, including the increased risks of suicidal and addictive behaviors. The impact of drug therapy for ADHD on such outcomes is poorly understood, hindering treatment decisions. A recent study in The BMJ conducted in a trial emulation design aimed to shed light on the associations of such outcomes with medical therapy for ADHD.

Introduction

About 5% of children and 2.5% of adults have ADHD worldwide. It is primarily diagnosed in childhood. Its negative impacts include a higher risk of suicidal behavior, substance abuse, accidental injuries, transport accidents, and criminal tendencies.

ADHD treatment includes pharmaceutical and non-pharmaceutical approaches, as well as combined strategies. Younger children, especially those with milder forms of ADHD, are often treated without drugs. However, ADHD medication, whether stimulant or non-stimulant, is widely used to treat older patients and can moderate the severity of core symptoms.

The effect of drug treatment on other functional outcomes remains unclear. Prior research has typically been restricted to cohorts fulfilling strict eligibility criteria, excluding about half the patients treated with drugs in clinical practice. Epidemiological studies indicate that these functional outcomes improve when the patient is put on ADHD drugs. However, these have not been controlled for the effects of time and include only patients who have experienced one or more of these outcomes.

The current study, therefore, sought to emulate a randomized controlled trial using observational data from Swedish national registries. This is termed the target trial emulation framework. It focused on first-time and recurrent events, selecting outcomes based on discussions with people with ADHD.

Study findings

The investigators identified 148,581 people newly diagnosed with ADHD, 60% were males. The median age was 17.4 years. They were followed up for two years for the five outcomes already mentioned.

About 57% of the patients were put on ADHD medication within three months of diagnosis. The most common primary drug was methylphenidate, prescribed to 88%, followed by atomoxetine (a non-stimulant) for 8%, and lisdexamfetamine for about 3%.

ADHD drug therapy was associated with a reduced rate of four of the five outcomes, all except accidental injuries.

Overall, the risk of suicidal behavior was 17% less in the drug treatment group, after adjustment for other confounding factors. Substance misuse incidence was 85% of that in the non-drug treatment group, and transport accident incidence was 88%. Criminality incidence was 13% less in the drug treatment group.

Recurrent event incidence

Recurrence of these undesirable outcomes is a common finding in ADHD. When only recurrent events were analyzed, the risk was reduced for all outcomes. Suicidal behavior risk was 15% lower, criminality and substance abuse were 25% less likely, and transport accidents were 16% lower, whilst accidental injuries showed a modest 4% reduction. This could reflect the higher odds of these patients having severe ADHD and thus responding more readily to drug therapy.

The effect of drug initiation was most pronounced among those patients who had a history of any of these outcomes. For instance, while drug treatment was associated with 13% lower rates of suicidal behavior in history-naïve individuals, there was a 21% decrease for those with a history of suicidal behaviors. This applied across all outcomes.

Type of drug

When comparing stimulants vs non-stimulants, the former appeared to be more beneficial, with the incidence rates of these outcomes being between 71% and 97% of the rates with the latter. The most significant difference was for substance abuse and criminality, the least being for accidental injuries.

Previous research supports these findings, with stimulants being shown to improve core ADHD symptoms better than non-stimulants. This could mitigate the risk of adverse functional outcomes in the long run. Most guidelines, therefore, advise the use of stimulants as first-line treatment for ADHD.

Demographic factors

Adults were likely to show more marked improvements in substance addiction and criminality, compared to children. Female patients had a more substantial reduction in criminality than males, even though earlier studies suggest that males are more likely to exhibit criminal behavior with ADHD. This may reflect a higher relative risk of such behavior among female ADHD patients.

The risk of recurrent suicidal behavior improved significantly with drug treatment in younger people compared to adults.

Conclusions

The study demonstrates for the first time that treating ADHD with drugs is associated with a reduced risk of suicidal behaviors and transport accidents in patients without a prior history; effects on substance misuse, accidental injuries, and criminality were not significant in this subgroup. In cases where such an event has already occurred, the risk for all five outcomes to recur was reduced with drug treatment.

Stimulants appeared to be associated with greater overall improvement; separately, reductions in recurrent suicidal behavior were significant in children and youths. These changes may be due to lower impulsivity and better attention and executive processing, as previous randomized controlled trials suggested. Less impulsive behavior may prevent criminal acts, and increased attentiveness may avert transport accidents.

While these findings corroborate prior studies’ findings, the changes observed are smaller. Perhaps this was because of the carefully considered study design that ensured the full spectrum of ADHD patients was represented, and not only those with a history of such outcomes who were on drug treatment. Moreover, in current practice, drug treatment is more readily initiated even with less severe symptoms.

As a result, this study yielded “average treatment effects more reflective of the entire patient population and closer to estimates expected from randomized controlled trials.”

The greater reduction in event rates for recurrent events compared to first-time events may suggest that “ADHD drug treatment may be associated with a true reduction in event rates rather than simply postponing the occurrence of these outcomes.”

The researchers also included type 1 diabetes as a negative-control outcome, which showed no association with ADHD medication, strengthening confidence in the causal interpretation. These findings could help develop practical guidelines for such therapy.

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