Adverse event reports involving diphenhydramine among adolescent and young adult patients increased following the appearance of the “Benadryl Challenge” on TikTok in 2020, according to findings presented at the American Academy of Pediatrics 2025 National Conference & Exhibition.
A total of 413 reports were identified in the US Food and Drug Administration (FDA) Adverse Event Reporting System between January 2013 and December 2024 among patients aged 10 to 25 years. The highest annual number of reports occurred in 2023 with 73 cases, followed by 62 cases in 2020. The lowest numbers were recorded in 2013 and 2016, with 7 cases each.
Monthly counts exceeded forecasted values during several months after the challenge began, including July 2020, December 2020, July 2021, February 2023, May 2023, January 2024, and June 2024. Forecasts had predicted between 2 and 7 cases monthly, but actual reports were higher during those months.
Diphenhydramine is a first-generation antihistamine with anticholinergic effects that can cause arrhythmias, seizures, coma, and death when misused. The challenge promoted ingestion of more than 300 mg to induce hallucinations or euphoria.
Researchers conducted a retrospective review of adverse event reports from January 2013 through December 2024, including cases involving single-ingredient diphenhydramine products in US patients. Excluded were duplicate reports, cases outside the US, reports involving multiple substances, or reports listing inconsistent reasons for use. Data from January 2013 to April 2020 were used to model expected monthly counts, which were then compared with observed counts from May 2020 through December 2024.
“While the increase in diphenhydramine-related adverse event reports may not be directly attributed to the 'Benadryl Challenge' the continued rise in cases among adolescents and young adults underscores a concerning national trend warranting health care provider attention,” said lead study author Noelia Swymeler, MD, pediatric resident physician of the University of Oklahoma at Tulsa School of Community Medicine.
Researchers emphasized that content encouraging dangerous use of the medication remained available online and highlighted the importance of clinician awareness and family safeguards.
Source: American Academy of Pediatrics
