Li, Lin, Zhu, Nanbo, Zhang, Le, Kuja-Halkola, Ralf, D’Onofrio, Brian M., Brikell, Isabell, Lichtenstein, Paul, Cortese, Samuele, Larsson, Henrik and Chang, Zheng (2024) ADHD Pharmacotherapy and Mortality in Individuals With ADHD. JAMA, 331 (10), 850-860. (doi:10.1001/jama.2024.0851).
Abstract
Importance: attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk.
Objective: to investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD.
Design, Setting, and Participants: in an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals 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 until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first.
Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis.
Main outcomes and measures: we assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings).
Results: of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). 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). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, −7.4 per 10 000 individuals; 95% CI, −14.2 to −0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, −1.6 per 10 000 individuals; 95% CI, −6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05).
Conclusions and relevance: among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.
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