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While attention deficit hyperactivity disorder (ADHD) is generally more prevalent in children, many adults are also affected. In fact, worldwide, approximately 5.9% of youths and 2.5% of adults have met the diagnostic criteria for ADHD.¹

More common in males than females, ADHD is caused by multiple genetic and environmental risk factors occurring in various combinations,¹ and is associated with a number of psychosocial functional impairments and adverse outcomes, including a twofold increase in mortality.² This increase is mainly due to unnatural causes, such as injury or poisoning, and does not appear to be associated with natural causes of death, such as respiratory problems or cancer.²

Management of ADHD typically consists of both nonpharmacological and pharmacological treatments, which may include either stimulant or nonstimulant medications.³ Previous studies examining the association between pharmacological treatment for ADHD and mortality have shown mixed results and had important limitations. Although ADHD treatment appears to reduce negative outcomes, such as injury, traffic collisions, and criminality, the long-term use of some medications may also increase cardiovascular risk.

Tapping the Swedish registries

These paradoxical outcomes prompted a nationwide population-based study with long-term follow-up to assess the association between the use of ADHD medication and mortality.³ An international team of researchers collected data from several Swedish national registries and used a target trial emulation approach, which applies principles of randomized trials to observational studies to help avoid certain key biases. Individuals ages 6 to 64 years who received an incident diagnosis of ADHD between January 1, 2007, and December 31, 2018, were identified, and those who had not taken ADHD medication for at least 18 months prior to their diagnosis were included in the analysis. 

Patients were followed from diagnosis of ADHD (baseline) until death, emigration, 2 years after baseline, or December 31, 2020, whichever came first. In sensitivity and subgroup analyses, 5-year mortality was also assessed. Main outcomes included all-cause and cause-specific mortality, which were further divided into natural and unnatural causes. Natural causes of death were defined as physical conditions, while unnatural causes included suicide, accidental poisoning or injuries, and other external injuries. 

ADHD, medication, and mortality

Overall, 148,578 individuals were included in the study, with a median age at baseline of 17.4 years; 41.3% were female and 58.7% were male.³ Within 3 months of an ADHD diagnosis, 56.7% of those studied initiated medication treatment, while 43.3% did not. During the 2-year follow-up, a total of 632 individuals died, while 1402 died during the 5-year follow-up.

During the 2-year follow-up period, the initiation of ADHD medication was associated with statistically significant lower risk of all-cause mortality (39.1 versus 48.1 per 10,000/risk difference 鈭�8.9 per 10,000, 95% confidence interval [CI] 鈭�17.3 to 鈭�0.6/adjusted hazard ratio [aHR] 0.79, 95% CI 0.70 to 0.88) and unnatural-cause mortality (25.9 versus 33.3 per 10,000/risk difference 鈭�7.4 per 10,000, 95% CI 鈭�14.2 to 鈭�0.5/aHR 0.75, 95% CI 0.66 to 0.86).

Initiation of medication, however, did not result in statistically significant improvement in risk of natural-cause mortality during the 2-year follow-up period (13.1 versus 14.7 per 10,000/risk difference 鈭�1.6 per 10,000, 95% CI 鈭�6.4 to 3.2/aHR 0.86, 95% CI 0.71 to 1.05). During the 5-year follow-up, however, the association remained statistically significant for the risk of unnatural-cause mortality (66.5 versus 70.5 per 10,000/risk difference 鈭�4.0 per 10,000, 95% CI 鈭�17.2 to 9.2/aHR 0.89, 95% CI 0.81 to 0.97).

Implications for ADHD treatment

The association between ADHD medication and improved mortality is an important one. 鈥淲e found among individuals diagnosed with ADHD, ADHD medication was significantly associated with lower mortality during a 2-year and 5-year follow-up period,鈥� stated first author Lin Li, PhD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, in an interview with 乌鸦传媒視頻, noting that the 鈥渞isk of death due to unnatural causes, such as accidents and overdoses, can be reduced by a quarter.鈥� These findings could impact current treatment guidelines and management algorithms, ultimately saving lives.

Nevertheless, more work is required in this area, Dr. Li added, mentioning the need for studies in populations outside of Sweden, as well as studies on the long-term effects of ADHD medications. Still, the significance of these new findings can鈥檛 be overlooked.

鈥淲ith such knowledge, doctors can tailor treatment plans for people with ADHD, in order to maximize the benefits of treatment and minimize the risks,鈥� Dr. Li concluded.

Published: June 28, 2024