Opioid deaths involving concurrent benzodiazepine use: Assessing risk factors through the analysis of prescription drug monitoring data and postmortem toxicology

Bannon, Michael J.; Jaster, Alaina M; Saad, Manal H.; Lenders, Jayna; Schmidt, Carl J.

doi:10.1016/j.drugalcdep.2021.108854

Cited by 11 publications

(9 citation statements)

References 11 publications

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“…It was a significant difference between the oxycodone-related fatal intoxications and other causes of death, where it was more frequent to have been dispensed a PDI drug in the fatal oxycodonerelated intoxications (OR 1.7). This is in accordance with a recent study by Bannon et al where the authors found a prescription for the benzodiazepine alprazolam as the single best predictor for fatal opioid intoxication, whereas a prescription of an opioid alone was not correlated to opioid death [14]. In our study, zopiclone, oxazepam, propiomazine, diazepam, and zolpidem were the most prevalent PDI co-prescribed drugs.…”

Section: Discussionsupporting

confidence: 93%

“…The combination of opioids and benzodiazepines has been defined as a risk factor for adverse effects. Concomitant opioid and benzodiazepine prescriptions have been proven to increase the risk of overdose [ 14 , 15 ]. In 2015, benzodiazepines were reported to be involved in nearly 30% of opioid overdose deaths in the US, and thus use and misuse of benzodiazepines was considered to contribute significantly to the opioid overdose epidemic [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

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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“…The international literature warns against prescribing alprazolam to particular ‘at-risk’ groups, including those with an increased risk of deliberate self-poisoning ( Austin et al., 2017 ; Isbister et al, 2004 ); those with a clinical history of substance abuse ( Darke et al, 2014 ); polysubstance drug users ( Darke et al, 2014 ), especially those taking opioids ( Bannon et al., 2021 ; Ojanperä et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Alprazolam-related deaths in Scotland, 2004–2020

et al. 2022

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Background: The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and consumption have increased. Concern about increasing numbers of alprazolam-related fatalities started circulating in 2018. However, statistics on this issue are very limited. This study examined patterns in such mortality in Scotland. Methods: Statistics on deaths where alprazolam was mentioned in the ‘cause of death’ were obtained from official mortality registers. Anonymised Scottish case-level data were obtained. Data were examined in respect of the characteristics of decedents and deaths using descriptive statistics. Results: Scotland registered 370 deaths in 2004–2020; 366 of these occurred in 2015–2020: most involved males (77.1%); mean age 39.0 (SD 12.6) years. The principal underlying cause of death was accidental poisoning: opiates/opioids (77.9%); sedatives/hypnotics (15.0%). Two deaths involved alprazolam alone. Main drug groups implicated: opiates/opioids (94.8%), ‘other benzodiazepines’ (67.2%), gabapentinoids (42.9%), stimulants (30.1%), antidepressants (15.0%). Two-thirds (64.2%) involved combinations of central nervous system (CNS) depressants. Discussion: Alprazolam-related deaths are likely due to an increasing illicit supply. The fall in deaths in 2019–2020 is partially due to increased use of designer benzodiazepines. Treatment for alprazolam dependence is growing. Clinicians need to be aware of continuing recreational alprazolam use. When such consumption occurs with CNS depressants, overdose and death risks increase. Conclusions: More awareness of alprazolam contributing to deaths, especially in conjunction with other CNS depressants, is needed by consumers and clinicians. Improved monitoring of illicit supplies could identify emerging issues of medicines’ abuse.

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“…In our study, the most prevalent co-prescribed drugs having pharmacodynamically interacting properties were zopiclone, oxazepam, propiomazine, diazepam, and zolpidem. In a study by Bannon et al, it was found that co-prescription of alprazolam was a better predictor for opioid-related death than prescription of an opioid alone that did not correlate to opioid death (135).…”

Section: Pharmacodynamically Interacting Drugs; Prescriptions and Fin...mentioning

confidence: 99%

Oxycodone in Forensic Toxicology : Analytical Strategies and Interpretation

Jakobsson

2022

Linköping University Medical Dissertations

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Opioid deaths involving concurrent benzodiazepine use: Assessing risk factors through the analysis of prescription drug monitoring data and postmortem toxicology

Cited by 11 publications

References 11 publications

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

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

Alprazolam-related deaths in Scotland, 2004–2020

Oxycodone in Forensic Toxicology : Analytical Strategies and Interpretation

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