That is according to a recent observational target trial emulation analysis that included 148,578 patients diagnosed with ADHD in Sweden. An article in the Journal of the American Medical Association reported that initial dispensation of ADHD medication was significantly associated with lower all-cause (hazard ratio [HR], 0.79) and unnatural-cause (HR, 0.75) mortality, but that the association with natural-cause mortality was not significant (HR, 0.86).
The Karolinska Institute–led study pointed out that ADHD is associated with increased risks of adverse health outcomes, including premature death, but it has been unknown whether ADHD pharmacotherapy influences the mortality risk. Researchers from Indiana University and New York University participated in the study.
The study included patients aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis and continued until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first.
For purposes of the study, ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. The researchers assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (e.g., physical conditions) and unnatural-cause mortality (e.g., unintentional injuries, suicide, and accidental poisonings).
In the study group, which was 41.3% female, 56.7% of the participants initiated ADHD medication. The median age at diagnosis was 17.4 years (interquartile range, 11.6-29.1 years).
The results indicated that the 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10,000 individuals) than in the noninitiation treatment strategy group (48.1 per 10,000 individuals), with a risk difference of –8.9 per 10,000 individuals (95% CI, –17.3 to –0.6).
Background information in the article noted that ADHD is the most prevalent neurodevelopmental condition, affecting 5.9% of youths and 2.5% of adults worldwide, according to the 2021 World Federation of ADHD International Consensus Statement. In the United States, the prevalence of ADHD is estimated to be 9.8% among children and adolescents and 4.4% among adults.
“The disorder is associated with a broad range of psychiatric and physical comorbidities, as well as adverse functional outcomes,” the authors advised. “Furthermore, individuals with ADHD have a 2-fold increased risk of premature death compared with those without it, mainly due to unnatural causes.”
For both children and adults diagnosed with ADHD, clinicians often recommend pharmacologic treatment, including stimulant and nonstimulant medications, as well as nonpharmacologic treatment. Past research indicated that ADHD medications are effective in reducing core ADHD symptoms and that risks are reduced for negative outcomes that could lead to mortality, including injuries, traffic collisions, and criminality. On the other hand, questions have been raised about the cardiovascular safety of ADHD medications, especially following long-term use, which could increase the mortality rate.
“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,” according to the authors, who added, “In contrast to the extensive literature on psychiatric and behavioral outcomes associated with ADHD medication, the impact of ADHD medication on physical comorbidities is less well understood. There is evidence that stimulants contribute to lower rates of smoking in adults, which could improve overall health.”
The study team further pointed out “concerns regarding the cardiovascular safety of stimulants.” The researchers added, “The results of the current study were reassuring because ADHD medication was not associated with increased risk of natural-cause mortality and, if anything, was associated with a reduced risk of natural-cause mortality in females. Nevertheless, future studies with larger sample sizes are warranted to confirm the relationship between ADHD medication use and natural-cause morbidity and mortality.”
The report noted that the initiation of ADHD medication was associated with a lower risk of all-cause and unnatural-cause mortality in males. “In females, the only observed statistically significant association was between initiation of ADHD medication and natural-cause mortality,” the authors explained. “Notably, females had a higher median age at baseline in our study, suggesting delayed ADHD diagnosis compared with males, and previous studies have also reported distinct patterns of psychiatric and physical comorbidities (e.g., females with ADHD have higher rates than males of depression, sleep disorder, atrial fibrillation, and asthma). Nevertheless, it is important to consider the difference in sample size and lower mortality rates in females when interpreting the results.”
The researchers called for further exploration of any sex difference in the relationship between ADHD treatment and mortality to optimize outcomes for both males and females with ADHD.
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