Over-the-counter antihistamines in drug-related deaths: a population-based case series
Authors: Oyekan P J , Gorton H C , Copeland C S 
Published: March 2021

Abstract

Introduction
Antihistamines are not one of the medicine groups reported on in the Office for National Statistics drug-related death data. (1) However, there is concern that first-generation antihistamines are misused for their sedative properties. This is amplified by a recent social media challenge, which resulted in deaths due to diphenhydramine overdose. (2) The extent of the involvement of antihistamines in deaths is largely unknown.

Aim
We aimed to evaluate deaths related to antihistamines in England (2000–2019) by individual drug, medicine classification (POM, P, GSL), whether the drug was considered attributable to the death (known as implication rate), or incidental; and examine temporal trends.

Methods
Deaths are reported voluntarily by coroners to the National Programme on Substance Abuse Deaths (NPSAD) in cases where psychoactive drugs were detected at post-mortem and/or when the decedent was known to abuse drugs. NPSAD holds data on decedent demographics (gender, age, employment status, living arrangements), details pertaining to the death (cause(s) of death, manner of death, conclusion of inquest, toxicology reports) and past social and medical histories, including drugs prescribed. From this dataset, we extracted all cases where an antihistamine was detected at post-mortem between 2000 and 2019. We report descriptive statistics to describe the reporting of antihistamines in deaths.

Results
We identified 1666 antihistamine detections from 1537 individuals. The significant majority of these were sedative antihistamines which are classed as pharmacy medicines (P) (85.2%, p&lt;0.01); deaths where prescription-only antihistamines were detected represented fewer than 7.0% of cases. Despite an increasing trend for antihistamine detections in deaths over time, the proportion of deaths where the detected antihistamine was implicated in causing the death declined over the same period (average implication rate 2000–2005: 58.7%; 2014–2019: 28.4%). Whilst death was deemed accidental in the majority of cases (66.1%), a significant proportion of cases were concluded as suicide (20.9%, p&lt;0.01).Polydrug use was evident in the vast majority of cases (98.5%), with central nervous system depressants the most commonly co-administered substances (94.8% of cases).

Conclusion
We describe the first report regarding antihistamine-related mortality from England. From the NPSAD, we can obtain prescription source and toxicology reports, beyond those reported in national death data. Although incomplete, the response from coroners is good (89%), and provides sufficient cause for concern. The rising trend in antihistamine-related deaths may in-part be contributed to by the perceived negligible dangers associated with antihistamines, both from the general public and professionals. Awareness of the dangerous sedative properties that some antihistamines possess is however heightened in individuals who are deliberately seeking out these effects. An urgent review of sedating antihistamines currently assigned under the P classification is needed to achieve antihistamine harm reduction, balanced against the self-care they enable.

References
1. Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2019 registration [internet]. 2020 [cited 18 Oct 2020]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2019registrations
2. US FDA. Benadryl (diphenhydramine): Drug Safety Communication - Serious Problems with High Doses of the Allergy Medicine. 2020.