Attention-deficit/hyperactivity disorder (ADHD) medications appeared to reduce the risk of suicide, drug misuse, transport incidents, and criminal activity, a new study showed.
After adjusting for covariates, ADHD medications were associated with a 17% reduction in suicidal behavior, a 15% decrease in substance misuse, a 13% reduction in criminality, and a 12% decrease in transport accidents.
Although randomized clinical trials have shown that ADHD medication can help alleviate core symptoms of the disorder, “there is less evidence on whether these symptom improvements translate to meaningful benefits in daily life,” principal investigator, Zheng Chang, PhD, and principal researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institute in Stockholm, Sweden, told Medscape Medical News.
The study was published online on August 13 in BMJ.
Five Key Real-World Outcomes
ADHD affects an estimated 15.5 million adults (6%) and 7 million children (11.4%) in the US, with the rate of diagnoses growing annually.
Randomized controlled trials often exclude a substantial portion of the population — approximately 50% of individuals taking ADHD medications — thereby limiting the applicability of the studies’ findings in clinical practice, the investigators noted.
A 2024 study of 113 randomized controlled trials led by Samuele Cortese, MD, PhD, and NIHR research professor at the University of Southampton, Southampton, England, showed that only stimulants and atomoxetine were effective at reducing the main symptoms of ADHD, such as hyperactivity and inattention.
Although previous research by Chang has linked ADHD medications to improved behavioral outcomes, this study is the first to employ target trial emulation to understand the relationship. Target trial emulation mimics randomized control trial design using observational data.
To gauge the efficacy of ADHD medication, the investigators analyzed data from 148,581 individuals aged 6-64 years (median age, 17.4 years; 41.3% women) from 2007 to 2020.
The data were pulled from Swedish national registers and included individuals with a new ADHD diagnosis who either initiated or did not initiate drug treatment within 3 months of diagnosis.
The researchers examined five key outcomes: substance misuse, accidental injury, transport accidents, criminality (any crime conviction), and suicidal behaviors based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.
To assess the effect of 2 years of sustained ADHD drug treatment on these outcomes, the researchers used data cloning, censoring, and inverse probability weighting. This approach was “designed to emulate the key features of randomized controlled trials and eliminate immortal time bias,” the investigators wrote.
In a secondary analysis, the researchers examined the association between treatment with ADHD medication and recurrent events of the study’s prespecified outcomes.
To avoid counting repeated treatment visits as outcome events, the study design only allowed for one event per month. The medications assessed in the emulated head-to-head trial included stimulants — methylphenidate, amphetamine, dexamphetamine, and lisdexamfetamine — and nonstimulants — atomoxetine and guanfacine.
Just over 50% of those started ADHD drug treatment within 3 months of diagnosis. Methylphenidate was the most frequently prescribed (88.4%) medication.
Stimulants were associated with lower event rates compared to nonstimulants.
After adjusting for covariates including sex, education level, age, comorbid physical or psychiatric conditions, and medical history, ADHD medications were associated with a reduced risk across all outcomes except accidental injuries.
However, among individuals with recurrent events, ADHD medications were linked to risk reductions across all five outcomes: 25% for criminality (95% CI, 0.71-0.79) and drug misuse (95% CI, 0.72-0.78), 16% for transport accidents (95% CI, 0.76-0.91), 15% for suicidal behaviors (95% CI, 0.77-0.93), and 4% for accidental injuries (95% CI, 0.92-0.99).
The study limitations included the lack of data on nondrug therapies and medication dosage. In addition, target trial emulation doesn’t account for other potential factors such as lifestyle choices or ADHD severity.
Experts Weigh-in
This study is the “first of its kind” to show beneficial effects of ADHD drugs on a broader range of clinical outcomes in the entire ADHD population, Cortese said in a press briefing for UK Science Media Center (SMC).
In a statement from SMC, some outside experts characterized the study as “landmark” research, while others like Ian Maidment, PhD, and professor of clinical pharmacy at Aston University in Birmingham, England, sounded a more cautious note.
“The databases have detailed information on dispensing, but we don’t know whether or not the patient took the medication. The study also couldn’t assess the impact of different doses and ethnicity is not reported. However, overall the study adds to our understanding of the potential benefits of these drugs,” he said.
See study for the full list of author disclosures.