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For patients with attention-deficit/hyperactivity disorder (ADHD), starting medication was associated with a significantly lower risk of death, particularly from "unnatural" causes, according to an observational Swedish study.

Among nearly 150,000 Swedish patients with ADHD, medication initiation was associated with a significantly lower rate of all-cause mortality over 2 years (HR 0.79, 95% CI 0.70-0.88) compared with not starting treatment, according to Zheng Chang, PhD, of the Karolinska Institute in Stockholm, and colleagues.

In particular, these patients had a significantly lower rate of mortality due to unnatural causes -- including unintentional injuries, suicide, and accidental poisonings -- over that time (HR 0.75, 95% CI 0.66-0.86), the researchers .

However, there was no difference in death from natural causes over that time, they found.

"ADHD is associated with a wide range of comorbidity, functional impairments, and premature mortality, particularly if left untreated," Chang told MedPage Today. "Timely diagnosis and treatment could reduce the risk of such adverse outcomes in youth and adults with ADHD."

Pharmacological treatment, including stimulant and non-stimulant drugs, is recommended for kids and adults with ADHD, as randomized controlled trials and epidemiologic studies have shown benefits for treatment. However, there are concerns about the cardiovascular safety of ADHD drugs, especially with long-term use.

"ADHD medications have the potential to reduce the risk of mortality," Chang said. "Nevertheless, clinical treatment decisions should involve a careful balancing of the benefits and risks at an individual level."

Chang and colleagues wrote that, to date, three studies have looked at the relationship between ADHD drugs and mortality, with mixed results. These studies have had a number of limitations, including a small number of deaths, indication bias, and a lack of a control group.

To account for some of these limitations, Chang and colleagues analyzed data from multiple Swedish national registries, identifying 148,578 patients ages 6 to 64 diagnosed with ADHD between 2007 and 2018. The median age at diagnosis was 17.4, and more than half of patients (58.7%) were male.

A total of 56.7% started ADHD medications -- methylphenidate (Ritalin), amphetamine (Adderall), dexamphetamine (Dexedrine), lisdexamfetamine (Vyvanse), atomoxetine (Strattera), or guanfacine (Intuniv) -- within 3 months of diagnosis, and 632 patients died during the 2-year follow-up.

Subgroup analyses revealed that ADHD medication initiation was associated with a lower rate of all-cause and unnatural-cause mortality in all age groups, and in males.

In females, starting ADHD drugs was associated only with a lower rate of natural-cause mortality (HR 0.64, 95% CI 0.45-0.90). Chang and colleagues noted that these gender differences should be explored further.

When extending the follow-up to 5 years, the association remained significant for unnatural-cause mortality (HR 0.89, 95% CI 0.81-0.97), the researchers said.

Chang and colleagues reported that ADHD drugs "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."

They did, however, caution that the study was limited by several factors, including its observational nature and its inability to account for unmeasured confounders. They also noted that some patients may not have consistently adhered to their prescribed medications.

In , Frances Levin, MD, of the New York State Psychiatric Institute in New York City, and colleagues noted that despite evidence "that ADHD medication improves morbidity and mortality in ADHD, this condition still goes undiagnosed and undertreated at high rates, particularly in adults with co-occurring substance use disorders, and in marginalized groups, including immigrants."

Chang and colleagues' study, they wrote, shows that "under-treating ADHD is not without consequences," noting that the healthcare workforce should be trained in "screening, diagnosing, and treating ADHD, just as has been done for other psychiatric disorders."

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