Association Between Stimulant Medication Use in Attention-Deficit/Hyperactivity Disorder (ADHD) and the Increased...

Area of Science:

• Neuroscience and Pharmacology
• Immunology
• Public Health

Background:

• Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition often treated with stimulant medications.
• The immunomodulatory effects of these stimulants and their potential impact on infection risk, particularly upper respiratory tract infections (URTIs), are not fully understood.
• Potential mechanisms linking stimulant use to increased infection risk include sympathetic nervous system activation, HPA axis modulation, sleep disturbances, and reduced salivary flow, all potentially impairing mucosal immunity.

Purpose of the Study:

• To investigate the association between stimulant medication use in ADHD patients and the risk of developing URTIs.
• To evaluate real-world data to determine if ADHD patients on stimulant therapy have a higher incidence of URTIs compared to those not on stimulants.

Main Methods:

• A retrospective cohort study was conducted using the TriNetX research network, encompassing de-identified electronic health records from over 170 million patients across 149 healthcare organizations.
• Two cohorts were defined: ADHD patients without stimulant prescriptions (control, n=1,798,001) and ADHD patients prescribed stimulants (medication cohort, n=1,099,756).
• The primary outcome was the diagnosis of URTI (ICD-10 J00-J06). Statistical analyses included risk estimates, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards modeling.

Main Results:

• The study included 2,897,757 ADHD patients. URTI incidence was higher in the stimulant medication cohort (31.2%) compared to the control group (28.5%).
• Stimulant exposure was associated with a statistically significant increase in URTI risk (risk ratio 1.095, odds ratio 1.138, hazard ratio 1.111).
• Kaplan-Meier analysis revealed significantly lower URTI-free survival in medicated ADHD patients, with median survival without URTI being shorter in the medication group (3176 days) versus controls (3757 days).

Conclusions:

• Patients with ADHD treated with stimulant medications demonstrated an approximately 11% higher relative risk of URTIs compared to unmedicated ADHD patients.
• Potential contributing factors include stimulant-induced immune suppression, sleep disruption, and xerostomia affecting mucosal defenses.
• These findings suggest that the association between stimulant use and increased URTI risk warrants consideration in the risk-benefit assessment of ADHD treatment, especially for individuals prone to infections.