Post mortem tissue distribution of quetiapine in forensic autopsies

Håvard Breivik,Joachim Frost,Trine N. Løkken,Lars Slørdal

doi:10.1016/j.forsciint.2020.110413

Abstract

The antipsychotic drug quetiapine is widely used, and increasingly prescribed off-label. Furthermore, quetiapine use has been linked to increased mortality rates, most likely due to a range of cardiovascular and metabolic adverse effects. This makes quetiapine a relevant substance in forensic toxicology casework. Quetiapine is believed to undergo significant post mortem redistribution. Herein, we present tissue distribution and concentration levels of quetiapine in post mortem whole blood, brain tissue, skeletal muscle, and liver tissue in a series of 14 quetiapine-implicated forensic autopsy cases along with the quetiapine concentrations determined in femoral whole blood in conjunction with the autopsies. Quantification was performed using liquid-liquid extraction and a validated UPLC-MSMS method. Six deaths were attributed to intoxication with quetiapine in combination with other substances; there were no quetiapine monointoxications. In eight cases, death was attributed to other causes than drug toxicity. In a majority of the cases, liver tissue contained the highest quetiapine concentrations, while whole blood levels were the lowest. Central (heart) blood concentrations were generally higher than peripheral (femoral) blood levels. Quetiapine concentrations in femoral blood correlated most strongly with concentrations in skeletal muscle. Otherwise, there was no consistent hierarchy of quetiapine tissue concentrations, and the tissue distribution showed no clear relationship with the length of the post mortem interval.

Highlights

Quetiapine is an atypical antipsychotic drug used in the treatment of schizophrenia and bipolar disorder [1]
Data suggest a higher mortality risk in quetiapine users compared to users of other atypical antipsychotic drugs [11]
Among the 14 forensic autopsy cases in which quetiapine was detected, 6 deaths were classified as mixed intoxications due to the presence of quetiapine and other potentially toxic substances, and 8 deaths were attributed to non-toxicological causes, e.g. motor vehicle accident, suicide and homicide

Summary

Introduction

Quetiapine is an atypical antipsychotic drug used in the treatment of schizophrenia and bipolar disorder [1]. A similar trend has been reported in a number of other Western countries [3,4,5,6]. This development is a cause for concern, as in addition to sedation, quetiapine may induce a range of adverse effects, including weight gain, hyperlipidemia and potentially fatal cardiac arrhythmias [7,8,9,10]. Data suggest a higher mortality risk in quetiapine users compared to users of other atypical antipsychotic drugs [11]

Methods

Results

Discussion

Conclusion