Investigating Potential Adverse Drug Reactions of Lisdexamfetamine Using Sequence Symmetry Analysis

Abstract

ABSTRACT The prevalence of ADHD is increasing rapidly, and lisdexamfetamine is increasingly popular, but few studies investigate its safety. We performed a sequence symmetry analysis (SSA) using Danish register data to identify potential ADRs associated with lisdexamfetamine in 2013–2023. Outcomes were incident prescriptions or incident discharge diagnoses. We calculated trend‐adjusted sequence ratios (SR) with 95% confidence intervals (CI). We additionally performed two comparator SSAs for the same outcomes following incident use of stimulants (methylphenidate and dexamfetamine) or non‐stimulants (guanfacine and atomoxetine). This study is reported according to RECORD‐PE guidelines. We included 48 740 incident lisdexamfetamine users with a median age of 24 years (IQR 16–35). SRs were calculated for 1426 exposure–diagnosis and 1337 exposure–prescription pairs. The 50 highest SRs from each category were evaluated. Among these, 28 exposure–outcome combinations had a 95% CI lower bound above 1. Of the 100 outcomes, 33 were considered known ADRs, while 60 were previously unknown. Two outcomes indicating increased urinary symptoms were identified (‘hematuria’, SR: 1.88 [95% CI: 1.25; 2.85] and ‘other urinary symptoms’, SR: 1.63 [1.20; 2.23]). We also identified serious gastrointestinal outcomes as a potential safety alert. Further investigation into these symptoms as potential ADRs is warranted.