ADHD Pharmacotherapy and Mortality in Individuals With ADHD

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.

Figure 1.. Flowchart of the Cohort Selection

^aThe 78 individuals who died or emigrated during the grace period contributed to both treatment strategies to avoid immortal-time bias. ADHD indicates attention-deficit/hyperactivity disorder.

Figure 2.. Association Between ADHD Medication Initiation and 2-Year Mortality Among Individuals With ADHD

Natural-cause mortality among those diagnosed with attention-deficit/hyperactivity disorder (ADHD) included death from somatic diseases and medical conditions (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], A00-R99, U07) and unnatural-cause mortality included death from suicide, accidental injuries, accidental poisoning, and other external injuries (ICD-10 codes, S00-T98, V01-Y98). ^aTwo-year absolute risk and 2-year risk difference were calculated per 10 000 individuals.

Figure 3.. Association Between ADHD Medication Initiation and 2-Year Mortality Among Individuals With ADHD Stratified by Age and Sex

Natural-cause mortality among those diagnosed with attention-deficit/hyperactivity disorder (ADHD) included death from somatic diseases and medical conditions (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes, A00-R99, U07) and unnatural-cause mortality included suicide, accidental injuries, accidental poisoning, and other external injuries (ICD-10 codes, S00-T98, V01-Y98). ^aTwo-year absolute risk and 2-year risk difference were calculated per 10 000 individuals.