University of Oklahoma Health Sciences Center

ADHD Pharmacotherapy and Mortality in Individuals With ADHD

Author/s:

Lin Li, Nanbo Zhu, Le Zhang, Ralf Kuja-Halkola, Brian M D'Onofrio, Isabell Brikell, Paul Lichtenstein, Samuele Cortese, Henrik Larsson, Zheng Chang

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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.

Keywords

ADHD ADHD treatment Death central nervous system stimulants

Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study

Author/s:

Xie, Y, Bowe, B, Yan, Y, Xian, H, Li, T, Al-Aly, Z

OBJECTIVE:

To estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).

DESIGN:

Longitudinal observational cohort study.

SETTING:

US Department of Veterans Affairs.

PARTICIPANTS:

New users of PPIs (n=157 625) or H2 blockers (n=56 842).

MAIN OUTCOME MEASURES:

All cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).

RESULTS:

There were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).

CONCLUSIONS:

Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

Keywords

proton pump inhibitors mortality peptic ulcer longitudinal study veterans

Medication Overload: America’s Other Drug Problem. How the drive to prescribe is harming older adults.

Author/s:

Executive Summary of the Lown Institute

In the last year, older adults in the U.S. sought medical care nearly 5 million times due to serious side effects from one or more medications. More than a quarter million of these visits resulted in hospitalizations, at a cost of $3.8 billion (see Appendix A in the full report). These numbers point to a rapidly growing epidemic of medication overload among older Americans. Over the last decade, adults age 65 and older have been hospitalized for serious drug side effects, called adverse drug events (ADEs), about 2 million times. To put this in context, there were 3.2 million opioid-related hospitalizations across the entire population during the same period.1 The trend of increasing ADEs is not propelled by drug abuse, but by the rising number of medications prescribed to older adults (called “polypharmacy” in the scientific literature). More than 40 percent of older adults take five or more prescription medications a day, a threefold increase over the past two decades.2,3 The greater the number of medications—most of which are prescribed for legitimate reasons—the greater the risk for serious adverse reactions in older patients. Medication overload is causing widespread yet unseen harm to our parents and our grandparents. It is every bit as serious as the opioid crisis, yet its scope remains invisible to many patients and health care professionals. While some clinicians are trying to reduce the burden of medications on their individual patients, no professional group, public organization, or government agency to date has formally assumed responsibility for addressing this national problem. If current trends continue, we estimate that medication overload will be responsible for at least 4.6 million hospitalizations between 2020 and 2030. It will cost taxpayers, patients and families an estimated $62 billion. Over the next decade, medication overload is expected to cause the premature death of 150,000 older Americans. In this report, the Lown Institute calls for the development of a national strategy to address medication overload and help older people avoid its devastating effects on the quality and length of their lives. A subsequent National Action Plan for Addressing Medication Overload will lay out a national strategy to address the epidemic of prescribing and ensure the safety of millions of older adults who are now at risk of preventable harm and premature death.

Keywords

polypharmacy medication overload hospitalization RISEOK elderly older adults Elderly care opioids

Mortality

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