Li, Lin, Zhu, Nanbo, Zhang, Le, Kuja-Halkola, Ralf, D'Onofrio, Brian M., Brikell, Isabell, Lichtenstein, Paul, Cortese, Samuele, Larsson, Henrik, and Chang, Zheng
Key Points: Question: Is initiation of attention-deficit/hyperactivity disorder (ADHD) medication associated with a reduced mortality risk in individuals with ADHD? Findings: In this observational, target trial emulation analysis that included 148 578 individuals diagnosed with ADHD in Sweden, initial dispensation of ADHD medication was significantly associated with lower all-cause (hazard ratio [HR], 0.79) and unnatural-cause (HR, 0.75) mortality, whereas the association with natural-cause mortality was not significant (HR, 0.86). Meaning: Among individuals diagnosed with ADHD, medication initiation was significantly associated with lower mortality, in particular for unnatural causes. 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. This cohort study investigates whether the initiation of medication to treat patients with attention-deficit/hyperactivity disorder (ADHD) was associated with mortality. [ABSTRACT FROM AUTHOR]