Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study

There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case–controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids

Drug Toxicity Deaths after Release from Incarceration in Ontario, 2006-2013: Review of Coroner’s Cases

<div><p>Background</p><p>There is an increased risk of death due to drug toxicity after release from incarceration. The purpose of this study was to describe the timing, rate and circumstances of drug toxicity deaths following release from incarceration. This information can be used to help design potential preventive interventions.</p><p>Methods and Findings</p><p>We reviewed coroner’s files to identify deaths in adults in Ontario between 2006 and 2013 caused by drug toxicity (n = 6,978) and these records were matched with provincial correctional records to identify individuals who died within one year of being released from incarceration (n = 702). Twenty percent (n = 137) of the 702 deaths occurred within one week of release. The majority (77%, n = 538) of deaths after release involved one or more opioids. Of the deaths involving opioids, intervention by another person may have been possible in 318 cases.</p><p>Conclusions</p><p>Between 2006 and 2013 in Ontario, one in ten drug toxicity deaths in adults occurred within one year of release from provincial incarceration. These findings may help to inform the implemention and assessment of interventions aimed at reducing drug toxicity deaths following release from incarceration.</p></div

Number of deaths by week since release in the year after release from provincial incarceration, 2006–2013.

<p>Number of deaths by week since release in the year after release from provincial incarceration, 2006–2013.</p

Characteristics of persons who died due to drug intoxication in the year after release from incarceration in Ontario, 2006–2013, n = 702.

<p>Characteristics of persons who died due to drug intoxication in the year after release from incarceration in Ontario, 2006–2013, n = 702.</p

Flow diagram of study participants.

<p>Flow diagram of study participants.</p

Expected and observed mean annual deaths for persons who died due to drug intoxication in the year after release from incarceration in Ontario, 2006–2013.

<p>Expected and observed mean annual deaths for persons who died due to drug intoxication in the year after release from incarceration in Ontario, 2006–2013.</p