Multisystem Sequelae of Chronic Diphenhydramine Misuse in an Adolescent: A Case Highlighting the Importance of Comprehensive History-Taking

Background: Diphenhydramine, an over-the-counter antihistamine, is increasingly misused by adolescents for its sedative and hallucinogenic effects. Despite its accessibility and perceived safety, chronic misuse poses serious risks, including neurologic, psychiatric, and gastrointestinal complications, especially in vulnerable youth with preexisting trauma or psychiatric illness. Case: We present a case of a teenage female with a history of traumatic brain injury, major depressive disorder, and restrictive eating disorder who was admitted following a diphenhydramine overdose. Her suicide attempt was preceded by a two-year history of undisclosed daily diphenhydramine misuse, initially for mood regulation and later escalating to dependency. Multisystem symptoms including seizures, disordered eating, and behavioral changes were retrospectively linked to her chronic use. Her TBI and initial seizure also coincided with a period of increased diphenhydramine ingestion, raising concern for misattributed or missed diagnoses. Discussion: This case highlights the diagnostic challenges posed by diphenhydramine misuse in adolescents. Chronic use can mimic or exacerbate psychiatric and neurologic conditions, delay appropriate intervention, and contribute to unnecessary polypharmacy or healthcare utilization. Her improvement with structured psychiatric care and medication discontinuation supports the role of early identification and trauma-informed management in preventing further harm. Conclusion: Diphenhydramine misuse should be considered in adolescents with overlapping psychiatric, neurologic, and gastrointestinal complaints. Routine psychosocial screening and awareness of non-traditional substances of abuse are essential for timely diagnosis and intervention.