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Initiating drug treatment forattention-deficit/hyperactivity disorder (ADHD) is associated with significantly lower all-cause mortality, particularly for deaths caused by accidental poisoning, suicide, or accidental injury, new data show. 

"ADHD medication may reduce the risk of unnatural-cause mortality by alleviating the core symptoms of ADHD and its psychiatric comorbidities, leading to improved impulse control and decision-making, ultimately reducing the occurrence of fatal events, in particular among those due to accidental poisoning," the investigators, with first author Lin Li, PhD, Karolinska Institutet in Stockholm, Sweden, wrote. 

The findings were published online on March 12 in JAMA. 

World's Most Prevalent Neurodevelopmental Condition

ADHD is the most prevalent neurodevelopmental condition, affecting about 5%-7% of youths and 3%-7% of adults worldwide. However, estimates show that in the United States, its prevalence is close to 9.8% in children and teens and 4.4% in adults, the investigators noted.  

Research has shown that pharmacologic treatment is effective in reducing the core symptoms of the disorder and reduces the risk for negative outcomes, including accidental injury and criminality. However, there are concerns about the cardiovascular safety of ADHD medications, particularly over the long-term, which could potentially increase mortality. 

Prior studies that examined the potential link between ADHD medications and mortality had important limitations and yielded mixed results, the authors noted. One "critical knowledge gap" not rigorously addressed by these earlier studies, they added, is the potential effect of ADHD medication on mortality in adults with the disorder.

Using national Swedish registries, the researchers examined whether initiation of medications to treat ADHD was associated with mortality in children, youth, and adults. 

Primary outcomes were all-cause and cause-specific mortality during a 2-year follow-up period. Specific causes of death were categorized into natural and unnatural. 

Investigators identified all individuals between ages 6 and 64 years with an incident diagnosis of ADHD between 2007 and 2018 who were medication-naive prior to diagnosis. 

They followed the cohort of 148,578 individuals (median age, 17 years; 59% male) from ADHD diagnosis until death, emigration, 2 years post-baseline, or to the end of 2020, whichever came first. In sensitivity and subgroup analyses, 5-year mortality as well as sex- and age-specific associations were also assessed. 

Prescribed ADHD medications included methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, atomoxetine, and guanfacine. 

Lower Mortality 

A total of 630 participants with ADHD died during the shorter 2-year follow-up, and 1400 died during the 5-year follow-up period. 

At 2 years, ADHD medication initiation was associated with a 21% lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70-0.88) and a 25% lower risk for unnatural death (HR, 0.75; 95% CI, 0.66-0.86). There was no association between groups in mortality from natural causes. 

Of interest, ADHD medication use was associated with a reduced mortality risk from natural causes among female participants but not unnatural causes. (HR, 0.64; 95% CI, 0.45 to 0.90).

The study shows an association and not a causal relationship, the investigators noted, pointing out that there are no data on lifestyle factors, which may have contributed to these correlations. 

'Noteworthy Findings'

In an accompanying editorial, Francis Levin, MD; Mariely Hernadez, PhD; and John Mariani, MD; Department of Psychiatry, Columbia University, New York, NY, noted that the study supports previous research that appropriate prescribing of ADHD medications can significantly reduce mortality. 

However, despite the evidence from this and other studies showing medication improves morbidity and mortality, ADHD "still goes undiagnosed and under-treated at high rates, particularly in adults with co-occurring substance use disorders and in marginalized groups, including immigrants," they wrote.

It's unclear how these "noteworthy findings" will translate into clinical practice, they added.

The study was conducted in Sweden, which has a universal government-support health system that lacks some of the barriers to healthcare access found in the United States and elsewhere, the editorialists noted. 

"Undertreating ADHD is not without consequences," they wrote, adding that more targeted training in screening, diagnosing, and treating ADHD is needed. 

The study was funded by the Swedish Research Council for Health, Working Life, and Welfare and the European Union's Horizon 2020 research and innovation program. Levin reported grants from the National Institutes of Health, the Substance Abuse and Mental Health Services Administration, the National Center for Advancing Translational Sciences, and US World Meds; nonfinancial support from Indivior Medication and research support from Aelis Pharmaceutical; royalties from the American Psychological Association, and consulting fees from MLB. Other disclosures are noted in the original article.