Alice in wonderland syndrome: Down the rabbit hole of VigiBase®

Alice in Wonderland Syndrome (AIWS) is a neurological disorder involving visual and perceptual distortions, such as altered size perception, sensations of levitation, and time distortion. Initially linked to migraines and epileptic seizures, AIWS has been associated later with tumors, infections, and both illicit and prescribed drugs. This study explores drug-related AIWS cases in the WHO global pharmacovigilance database, VigiBase®, with a focus on age-specific patterns. We queried VigiBase® for AIWS reports until December 15, 2024 and categorized them into pediatric and adult groups. Disproportionality analyses identified drug-AIWS associations using the lower bound of the confidence interval of the Information Component (IC₀₂₅). We conducted sensitivity analyses, with a focus on healthcare professionals reports and excluding COVID-19 cases. We identified 87 AIWS cases: 26 (29.9 %) pediatric and 45 (51.7 %) adult. Most (64.4 %) were serious, with recovery documented in 79.6 %. COVID-19 vaccines, montelukast, and aripiprazole were most frequently reported. Montelukast showed the strongest signal in both adults (IC 4.2[3.2-5.0]) and children (IC 3.2[1.7-4.2]), followed by methylphenidate in pediatric cases (IC 2.3[0.3-3.5]). Adults showed signals for sertraline (IC 3.4[2.1-4.4]), topiramate (IC 3.1[1.3-4.2]), and aripiprazole (IC 2.1[3.5-4.4]). Signal consistency was confirmed by both sensitivity analyses. This study sheds light on age-dependent profiles of drug-associated AIWS. Montelukast, aripiprazole, sertraline, and topiramate were disproportionately associated, consistent with prior case reports. Clinicians should consider AIWS when visual distortions arise during such treatment, particularly in youths treated with methylphenidate or montelukast. While typically reversible, AIWS warrants clinical awareness and careful risk-benefit assessment. As causality cannot be established, further population-based studies are needed to confirm these findings.