Background: 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.
Objectives: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD.
Methods: Design, Setting and Participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6-64 years with an incident diagnosis of ADHD between 2007-2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, two years after ADHD diagnosis, or December 31st, 2020, whichever came first. Exposures: ADHD medication initiation was defined as dispensing of ADHD medication within three months of ADHD diagnosis. Main Outcomes and Measures: We assessed all-cause mortality within two years after ADHD diagnosis, as well as natural-cause (e.g., physical conditions) and unnatural-cause (e.g., unintentional injuries, suicide, and accidental poisonings) mortality. We further assessed the age- and sex-specific associations.
Results: Of 148,578 individuals with ADHD (61,356 [41.3%] females), 84,204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 (interquartile range, 11.6-29.1) years. The two-year mortality risk was lower in the initiation treatment strategy (39.1/10,000 individuals) than the non-initiation treatment strategy (48.1/10,000 individuals), with a risk difference of -8.9/10,000 individuals (95% CI= -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause (HR=0.79, 95% CI=0.70-0.88) and unnatural-cause mortality (two-year mortality risk 25.9/10 000 individuals vs 33.3/10,000 individuals; risk difference=-7.4/10 000 individuals, 95%CI=-14.2 to -0.5; HR=0.75, 95% CI=0.66-0.86), but not for natural-cause mortality (two-year mortality risk=13.1/10,000 individuals vs 14.7/10,000 individuals; risk difference=-1.6/10,000 individuals, 95%CI=-6.4 to 3.2; HR=0.86, 95% CI=0.71-1.05).
Conclusions: Among individuals diagnosed with ADHD, ADHD medication initiation was significantly associated with lower mortality, particularly for death due to unnatural causes.
