Postmortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations

Bech, Anne Berit; Clausen, Thomas; Waal, Helge; Vindenes, Vigdis; Edvardsen, Hilde Marie Erøy; Frost, Joachim; Skeie, Ivar

doi:10.1111/add.15211

Cited by 15 publications

(20 citation statements)

References 33 publications

(61 reference statements)

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“…Drug users seem to have discovered that BZDs are able to enhance the positive subjective effects of opiates [24]. Today, abundant evidence has been published on the significant co-use of BZDs and opiates [54,55]. It should be noted that the prevalence of BZD use among patients maintained on methadone ranges between 51% and 70% and rates close to this range also have been reported for patients on buprenorphine [56] and in active heroin users [24].…”

Section: Discussionmentioning

confidence: 99%

Medical Psychotropics in Forensic Autopsies in European Countries: Results from a Three-Year Retrospective Study in Spain

Almeida-González

Boada

Hernández

et al. 2022

Toxics

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Medical psychotropics are widely used and prescribed in developed countries. These medications may have an impairing effect on mood or perception and may induce harmful behaviors. Nevertheless, in Europe, studies on their importance from a medico-legal perspective are scarce. To fill this gap, we evaluate the determinants of these drugs in a retrospective study based on data obtained from forensic autopsies. Toxicological analyses were performed on 394 blood samples from compulsory autopsies at the Institute of Legal Medicine of Las Palmas. Of the samples, 41% (159) were positive for at least one psychotropic, with benzodiazepines being the most frequently detected (24.1%), followed by opiates and antidepressants. Benzodiazepines, opiates, and antidepressants were detected more frequently in men who suffered a violent death. More than 30% of the positive samples showed two or more drugs, suggesting a prevalence of polypharmacy among forensic autopsy subjects, with the most frequently combination found being benzodiazepines plus opiates (28.3% of positive samples). A combination of opiates plus antidepressants was also found in subjects involved in violent deaths. Our results suggest that more than 40% of the adult European population involved in medico-legal issues may be under the influence of legal psychotropics. The link between violent deaths and the use of medical psychotropics is particularly worrisome and indicates that these drugs should be carefully monitored in developed countries, in all forensic autopsies, in a similar way to illegal psychotropics.

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Section: Discussionmentioning

confidence: 99%

Medical Psychotropics in Forensic Autopsies in European Countries: Results from a Three-Year Retrospective Study in Spain

Almeida-González

Boada

Hernández

et al. 2022

Toxics

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“…Nearly 45% of the patients prescribed oxycodone had a concomitant prescription of diazepam [ 18 ]. Bech et al studied the association between drug-induced cause of death and benzodiazepines among patients in Norway receiving opioid agonist treatment, and found that 76% of the cases had at least one benzodiazepine on board at time of death [ 19 ]. Combined use of alcohol and opioids is also associated with PDI effects, causing increased risk for respiratory depression.…”

Section: Introductionmentioning

confidence: 99%

Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions

Jakobsson

Gustavsson

Jönsson

et al. 2022

Eur J Drug Metab Pharmacokinet

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Background and ObjectivesOxycodone is frequently prescribed as well as detected in postmortem cases. Concurrent use of pharmacodynamically or pharmacokinetically interacting drugs can cause adverse effects or even fatal intoxication. The aims of this study were to investigate differences in prescriptions for and toxicological findings of pharmacodynamically and pharmacokinetically interacting drugs in fatal oxycodone-related intoxications and other causes of death. We also aimed to investigate the differences in prevalence of oxycodone prescriptions, and the detected postmortem oxycodone concentrations between fatal oxycodone-related intoxications and other causes of death. Methods Forensic autopsy cases (2012)(2013)(2014)(2015)(2016)(2017)(2018) where oxycodone was identified in femoral blood (n = 1236) were included. Medical history and prescription data were retrieved from national databases and linked to the forensic toxicology findings. Results Oxycodone-related deaths were found to have higher blood concentrations of oxycodone (median 0.30 µg/g vs. 0.05 µg/g) and were less likely to have a prescription for oxycodone (OR 0.62) compared to nonintoxication deaths. Pharmacodynamically interacting drugs were prescribed in 79% and found in blood in 81% of the cases. Pharmacokinetically interacting drugs were rarely prescribed (1%). Oxycodone-related deaths were more likely to have prescriptions for a pharmacodynamically interacting drug (OR 1.7) and more often have co-findings of one or multiple pharmacodynamically interacting drugs (OR 5.6). ConclusionThe results suggest that combined use of oxycodone and pharmacodynamically interacting drugs is associated with oxycodone-related death and that non-medical use of oxycodone is a potential risk factor for oxycodone-related intoxication.

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“…One possible explanation for this finding, in addition to the large increase in the number of patients in treatment, may be that OST-patients are not being discharged from treatment to the same extent as before the introduction of the patient choice reform, in combination with the changes in national guidelines, as presented in a previous study [19]. In line with this, a recent study from low-threshold OST programs in Norway found that more than half of the deaths during OST over 2 years were drug-induced [59]. The authors express concern about the large number of cases where an opioid, including the patient's prescribed OST medication, was the main intoxicant in overdose deaths.…”

Section: Discussionmentioning

confidence: 67%

“…Higher pooled concentrations of opioids were found among the drug-induced deaths compared to those who died from other causes. Among the deceased in overdose who were prescribed buprenorphine, other opioids (mainly heroin) were found to a high extent [59]. In our study, we have not investigated the concentration of substances at death, nor do we know which opioid caused the deaths in the individuals who were on OST at time of death.…”

Section: Discussionmentioning

confidence: 85%

Changes in opioid-related deaths following increased access to opioid substitution treatment

Andersson

Håkansson

Berge

et al. 2021

Subst Abuse Treat Prev Policy

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Background Opioid-related mortality is high and increasing in the Western world, and interventions aimed at reducing opioid-related deaths represent an important area of study. In Skåne County, Sweden, a patient choice reform resulted in increased access to opioid substitution treatment (OST). In addition, a gradual shift towards less restrictive terms for exclusion from OST has been implemented. The aim of this study was to assess the impact of these policy changes on opioid-related deaths. Methods Detailed data on opioid-related deaths in Skåne during the 2 years prior to and following the policy change were obtained from forensic records and from health care services. Data on overdose deaths for Skåne and the rest of Sweden were obtained using publicly available national register data. Time periods were used as the predictor for opioid-related deaths in the forensic data. The national level data were used in a natural experiment design in which rates of overdose deaths were compared between Skåne and the rest of Sweden before and after the intervention. Results There was no significant difference in the number of deaths in Skåne between the data collection periods (RR: 1.18 95% CI:0.89–1.57, p= 0.251). The proportion of deaths among patients enrolled in OST increased between the two periods (2.61, 1.12–6.10, p= 0.026). There was no change in deaths related to methadone or buprenorphine in relation to deaths due to the other opioids included in the study (0.92, 0.51–1.63, p= 0.764). An analysis of national mortality data showed an annual relative decrease in unintentional drug deaths in Skåne compared to the rest of Sweden following the onset of the reform (0.90, 0.84–0,97, p= 0.004). Conclusions Opioid-related deaths, as assessed using forensic data, has not changed significantly in Skåne following a change to lower-threshold OST. By contrast, national level data indicate that the policy change has been associated with decreased overdose deaths. The discrepancy between these results highlights the need for more research to elucidate this issue. The result that more patients die during ongoing OST following an increase in access to treatment underlines the need for further preventive interventions within the OST treatment setting.

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Postmortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations

Cited by 15 publications

References 33 publications

Medical Psychotropics in Forensic Autopsies in European Countries: Results from a Three-Year Retrospective Study in Spain

Medical Psychotropics in Forensic Autopsies in European Countries: Results from a Three-Year Retrospective Study in Spain

Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions

Changes in opioid-related deaths following increased access to opioid substitution treatment

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