Characterization of Diphenhydramine-Related Accidental Overdose Deaths

Abstract

Characteristics of diphenhydramine (DPH)-induced accidental overdose deaths were compared to deaths without DPH present. Data from 4702 drug-induced deaths during 2005 to 2011 in four states were reviewed, with 3884 of these certified as accidental. DPH was involved in 276 cases (5.9%), with the manner of death ruled accidental in 181 (DPH group). The remaining 3703 accidental deaths constituted the control group. Age, body mass index, and the cases with benzodiazepine or opioid co-intoxicants did not differ significantly between groups. In the DPH deaths, methadone was the most frequently identified additional co-intoxicant, particularly when only one or two other co-intoxicants were present. Significantly more females (57.5% vs. 31.5%, respectively) and co-intoxicants were present (55.8% vs. 20.1% with ≥ 3 other co-intoxicants present, respectively) in the DPH compared to the control group. Alcohol was identified significantly less often in DPH decedents. Antidepressants overall and the selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) classes appeared significantly more often as co-intoxicants in DPH decedents compared to controls. Female DPH decedents were also significantly more likely than control females to have antidepressants (32.7% vs. 16.8%, respectively), TCAs (16.4% vs. 7.1%), or SSRIs present (21.2% vs. 11.6%). DPH concentrations in the accidental deaths were usually lower compared to the suicides although overlap was present. In conclusion, the availability of over-the-counter DPH appears to pose significant potential for drug abuse and should be identified as contributory to death with other detected co-intoxicants such as antidepressants, benzodiazepines, opioids, and other central nervous system depressant drugs.

Additive Effects of Cointoxicants in Single-Opioid Induced Deaths

“…As a result, even though some of the individual associations appear to be fairly small, their possible additive contributions in opioid-related deaths could be substantial. For example, a previous analysis of DPH deaths found that over half of the DPH-related fatalities involved four or more drugs, with antidepressants often found as cointoxicants (8). Thus, in a hydrocodone-related death with a concentration of 0.08 μg/mL found on toxicological analysis, if DPH, a TCA, and alprazolam were also found to be cointoxicants, the additive effects of those cointoxicants in our model (−0.028 + −0.016 + −0.022), respectively, on the hydrocodone concentration might be comparable to an actual hydrocodone concentration of 0.146 μg/mL, almost double the concentration actually found.…”

“…Cointoxicants often present with opioids in drug-related deaths include benzodiazepines, alcohol, and antidepressants (5)(6)(7). Diphenhydramine was also found to be a cointoxicant in almost 6% of West Virginia drug-induced deaths (8). It is well known that alcohol and drugs with central nervous system depressant effects can exert additive or synergistic toxic effects when used in conjunction with opioids (5).…”