In a recent study published in Eye, researchers assessed the risks of open-angle glaucoma (OAG) and angle closure glaucoma (ACG) among users of attention-deficit/hyperactivity disorder (ADHD) medications.
Study: Medications for attention deficit hyperactivity disorder associated with increased risk of developing glaucoma. Image Credit: Creativan/Shutterstock.com
Background
ADHD is a neurodevelopmental disorder caused by delayed maturation of noradrenaline and dopamine transmission in the prefrontal cortex. It is characterized by developmentally inappropriate impulsivity, inattention, and hyperactivity.
It affects an estimated 4% of adults and 5% to 10% of children in the United States (US). Current ADHD therapies include non-stimulants and stimulants.
Psychostimulants, such as methylphenidate and amphetamines, are the first-line therapy, given their increased efficacy. Further, non-medical use of prescription stimulants (NUPS) has been growing in youth, especially in university and secondary school students; a 2005 report estimated that the prevalence of NUPS was up to 25% in US colleges. NUPS-related emergency room visits increased by 156% between 2006 and 2011.
Stimulants act on the central nervous system (CNS) and inhibit the reuptake of norepinephrine and dopamine in the synaptic cleft. However, methylphenidate and amphetamines may induce or aggravate ACG due to their sympathomimetic amine functionality.
Further, reports link methylphenidate usage with cataract formation, mydriasis, increased intraocular pressure (IOP), and accommodation abnormalities.
About the study
In the present study, researchers investigated the risk of OAG and ACG in patients using ADHD medications. They used data from the IQVIA PharMetrics Plus database. Patients newly prescribed methylphenidate, amphetamines, or atomoxetine during 2010-20 were included.
Regular ADHD medicine users had ≥ one prescription every three months within one year before glaucoma diagnosis.
Current users had ≥ one prescription within three months before glaucoma diagnosis. Diagnoses were captured using the International Classification of Diseases, 9th (ICD-9) and 10th (ICD-10) editions, and Clinical Modification codes.
The team aggregated OAG and ACG codes into a new “combined glaucoma cases” category. Patients were followed up until the first diagnosis of OAG or ACG.
Four age-matched controls were assigned to each case. Demographic characteristics of cases and controls were examined using descriptive statistics.
Incidence rate ratios (IRRs) of glaucoma among ADHD medication users were estimated and compared with non-users using conditional logistic regression, adjusted for confounding factors (age, sex, topiramate use, myopia, and hyperopia).
Findings
The cohort initially comprised 462,962 patients newly prescribed ADHD medications during 2010-18. After exclusions, 240,257 were retained for analysis.
Of these, 6.6% used atomoxetine, 33.8% used methylphenidate, 44.5% used amphetamines, and 15% used a combination. In total, there were 1,159 cases of incident glaucoma and 4,636 controls.
Cases and controls had a similar distribution of covariates and were aged 45.4, on average. Subjects were followed up for a mean of 1.8 years. The use of methylphenidate was associated with a higher adjusted IRR (aIRR) of OAG, while that of amphetamines or atomoxetine was not associated with an increased OAG aIRR.
Contrastingly, using amphetamines or atomoxetine was associated with an increased aIRR of ACG, whereas methylphenidate use was not associated with elevated aIRR of ACG. Notably, the aIRRs for OAG or ACG were similar for current and regular users of methylphenidate or amphetamines.
Regular atomoxetine users showed increased aIRR for ACG, but current users exhibited no precise increases in aIRR.
Conclusions
In sum, the study investigated the risk of OAG and ACG among ADHD medication users. The findings highlight that amphetamine and atomoxetine users had a higher risk of ACG but not OAG.
By contrast, methylphenidate users were at an increased risk of OAG but not ACG. The study’s limitations include the relatively short follow-up and the lack of dose-dependent analyses.
Further, the researchers could not control for all potential confounders. Additional studies are required to corroborate the associations and investigate whether the dose and duration of the treatment could impact the risk.
The authors believe a careful ophthalmologic examination and annual IOP assessment would benefit ADHD patients. They suggest that young people should be informed about the potential side effects of the recreational use of these medications.
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