Association of ADHD Pharmacotherapy With Mortality in Individuals With ADHD
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
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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Additional Info
Disclosure statements are available on the authors' profiles:
ADHD Pharmacotherapy and Mortality in Individuals With ADHD
JAMA 2024 Mar 12;331(10)850-860, L Li, N Zhu, L Zhang, R Kuja-Halkola, BM D'Onofrio, I Brikell, P Lichtenstein, S Cortese, H Larsson, Z ChangFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Does treating ADHD reduce mortality?
For a very long time, clinicians did not want to treat ADHD with stimulant medications because of the fear of addiction associated with these medications. Then, as we moved into adult ADHD, there was fear about the medications affecting cardiac health. There was always fear about these therapies causing harm.
In studies in which patients got treatment, they seemed to have fewer rates of injuries, traffic collisions, and criminality issues, and this trend should lead to a decreased risk of mortality. However, no study has ever shown a clear mortality benefit. This study used the Swedish database including 148,578 patients with ADHD to try and determine whether mortality is reduced with treatment.
The authors examined patients aged between 6 and 64 years with ADHD and compared those who were treated with those who were not. Furthermore, they looked at the 2-year mortality rates. The median age at diagnosis was 17.4 years (IQR, 11.6–29.1 years).
The 2-year mortality risk was lower in the group that had treatment (39.1 deaths per 10,000 individuals) versus (48.1 per 10,000 individuals). The relative risk reduction for all-cause death was 21% in favor of the treatment group (HR, 0.79; 95% CI, 0.70–0.88). There was no difference between the two groups with regard to natural-cause mortality. However, there was a substantial (25%) reduction (HR, 0.75; 95% CI, 0.66–0.86) in unnatural-cause deaths (eg, suicide, accidental injuries, accidental poisoning, and other external injuries), which basically accounts for most of the benefit observed with the treatment.
So, by managing the symptoms of ADHD, accidents and self-harm events are reduced.
Perhaps our fear of these medications may be overstated. Of course, we still have to use formulations that reduce abuse potential and we need to make sure that there are no underlying cardiac issues before starting these medications. However, it may be time for us to embrace these therapies, considering that they have potential benefits with regard to mortality.