Nasal Adverse Events Associated With Attention-Deficit Hyperactivity Disorder (ADHD) Medications: A Systematic Review, Meta-Analysis, and Implications for the Otolaryngologist

注意力缺陷多动障碍 (ADHD) 药物相关鼻部不良事件:系统评价、荟萃分析及其对耳鼻喉科医生的启示

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Abstract

This systematic review and meta-analysis aims to determine the incidence of nasopharyngitis and sinusitis associated with stimulant and non-stimulant attention-deficit hyperactivity disorder (ADHD) medications and to assess whether differences exist between drug classes or compared with placebo. Studies published up to 1 August 2025 of adult patients receiving licensed ADHD medications reporting nasal adverse events were included from MEDLINE, Embase, Cochrane, Web of Science, and PsycINFO. Pooled incidence was calculated, and forest plots were constructed for placebo-controlled studies. Subgroup analyses by follow-up duration were performed to explore temporal effects. Risk of bias was assessed, and certainty of evidence was determined using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A total of 18 studies with 5,468 patients met the inclusion criteria, and an additional two articles were used in the subgroup analysis. The pooled incidence of nasopharyngitis was 11.3% (n = 1880) for stimulants and 9.1% (n = 3588) for non-stimulants. Meta-analyses of placebo-controlled studies revealed no significant difference in nasopharyngitis risk between stimulant (RR = 1.09, 95% CI 0.84-1.40) or non-stimulant (RR = 0.91, 95% CI 0.62-1.33) medications and placebo. A Bucher indirect comparison demonstrated no significant differences in nasopharyngitis incidence between drug classes (RR = 1.2, 95% CI 0.76-1.9). Sinusitis occurred in 6.6% (n = 381) and 5.5% (n = 541) of stimulant and non-stimulant users, respectively. Subgroup analysis suggested higher nasopharyngitis rates in stimulant users after 12 months, up to 17% (n = 1018), whereas non-stimulant rates remained consistent over time. Neither stimulant nor non-stimulant ADHD medications were significantly associated with an increased risk of nasopharyngitis or sinusitis compared with placebo. Nevertheless, a subtle trend toward higher incidence with prolonged stimulant use suggests a potential long-term effect. In cases where alternative causes have been excluded, otolaryngologists should remain aware of this possible association. Based on these findings, we propose practical clinical considerations and future research priorities to guide ENT clinicians in optimising the management of ADHD patients with nasal symptoms.

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