An unusual case of risperidone instability in a fatality presenting an analytical and interpretative challenge

Abstract

This paper describes the detection and characterization of unusual metabolite/breakdown products of the anti-psychotic drug risperidone in post-mortem blood and urine as part of a toxicological investigation into an unexpected death of a male suffering from paranoid schizophrenia prescribed risperidone and previously paroxetine. Compounds detected in the post-mortem blood and urine specimens were shown to be benzisoxazole ring scission products of risperidone and a hydroxy metabolite. These compounds are never routinely detected in blood and urine but can be present in mammalian faeces indicating that gut bacteria could be responsible for their formation. In this case, evidence for this process was demonstrated by the controlled in vitro stability study of risperidone spiked into the case blood and urine leading to the hypothesis that the post-mortem blood and urine samples analyzed could have contained bacteria with the ability to breakdown risperidone and its metabolite in this way. This finding is very unusual and has not been encountered before in any previous risperidone cases investigated by the authors, or widely reported in the post-mortem toxicological literature. However, a recently published paper has supported these findings in blood. As a result of this work, it was shown that the deceased had taken risperidone prior to death, even in the absence of any risperidone or its hydroxy metabolite(s) in the blood and urine. Given that risperidone has been reported to interact with paroxetine, the ingestion of risperidone could have been a factor that contributed to the death.

Antemortem and postmortem influences on drug concentrations and metabolite patterns in postmortem specimens

“…A similar case was reported by another group (Taylor & Elliott, ). The deceased was found dead in his home and was known—among others—to be on prescription with risperidone.…”

“…HPLC–DAD stability results of risperidone spiked into equine blood and case blood showing production of the suspected risperidone scission product. (Reprinted with permission from Taylor and Elliott (). Copyright 2013 Wiley)…”

The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management

“…Gut microbiota have been shown to participate in the reductive metabolism of psychotropic medications such as the benzodiazepine clonazepam . Risperidone, an atypical antipsychotic, has been shown in postmortem studies to undergo gut‐mediated isoxazole scission . In addition, studies with levodopa, a mainstay in the treatment for Parkinson disease, show that the presence of Helicobacter pylori is associated with decreased plasma levels of the drug .…”

“…29 Risperidone, an atypical antipsychotic, has been shown in postmortem studies to undergo gut-mediated isoxazole scission. 30 In addition, studies with levodopa, a mainstay in the treatment for Parkinson disease, show that the presence of Helicobacter pylori is associated with decreased plasma levels of the drug. 31 Although the pharmacokinetics of these medications may, in part, be altered by the microbiome, there are currently no defined clinical consequences of these occurrences.…”

Визначення Рисперидону В Біологічному Матеріалі Методом Ультраефективної Рідинної Хроматографії

“…Даний препарат призначають у дозі від 0,5 до 8 мг/денно. При передозуванні спостерігають-ся побічні ефекти, серед яких найнебезпечнішими для життя є кардіотоксична дія препарату, спричине-на подовженням інтервалу QT на ЕКГ, та злоякісний нейролептичний синдром [4,5]. Описано смертельні випадки отруєнь рисперидоном [6].…”