Dose-dependent toxicity of diphenhydramine overdose

Background: Diphenhydramine (DPHM) overdose is a frequent cause of acute po isoning. Although its clinical features are well known, information about t he dose-dependent toxicity of DPHM is still scarce. The objective of this s tudy was to investigate the dose-dependent toxicity of DPHM in patients wit h acute DPHM poisoning. Methods: We have analyzed retrospectively all well-documented cases with DP HM monointoxications reported by physicians to the Swiss Toxicological Info rmation Centre (STIC) between January 1984 and April 1996. In addition, a p rospective study focusing on ingested DPHM I doses and severity of symptoms was performed between May 1996 and December 1998. Results:The retrospective and prospective studies included 232 and 50 patie nts with DPHM monointoxications, respectively. In both studies, mild sympto ms (somnolence, anticholinergic signs, tachycardia, nausea/vomiting) occurr ed in 55-64%, moderate symptoms (isolated and spontaneously resolving. agit ation, confusion, hallucinations and ECG disturbances) in 22-27% and severe symptoms (delirium/psychosis, seizures, coma) in 14-18% of patients. Moder ate symptoms occurred above ingested doses of 0.3 g DPHM. For severe sympto ms the critical dose limit was 1.0 g DPHM. Although the frequency of deliri um/psychosis remained constant or even decreased, coma and seizures were si gnificantly (p<0.05) more frequent in the >1.5-g compared with the 1.0- to 1.5-g-dose group. Conclusions: These data demonstrate a clear dose-dependent acute toxicity o f DPHM. They indicate that only patients with DPHM ingestions above 1.0 g a re at risk for the development of severe symptoms and, therefore, should be hospitalized. Thus, the results contribute to the data basis required for a cost effective management of patients with DPHM overdose.