Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover study

Teng-Chou Chen; Roger D Knaggs; Li-Chia Chen

doi:10.1016/j.bja.2021.06.049

Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover study

Teng-Chou Chen, Roger D Knaggs, Li-Chia Chen

Pharmacy

Nottingham University Hospital NHS Trust

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care.

METHODS: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows.

RESULTS: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06-4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01-5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02-9.04) significantly increased the risk of ORD.

CONCLUSIONS: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day-1 and the combination of opioids and gabapentinoids, even with low opioid doses.

Original language	English
Pages (from-to)	789-797
Number of pages	9
Journal	British Journal of Anaesthesia
Volume	127
Issue number	5
Early online date	18 Aug 2021
DOIs	https://doi.org/10.1016/j.bja.2021.06.049
Publication status	Published - Nov 2021

Keywords

Adult
Aged
Aged, 80 and over
Analgesics, Opioid/administration & dosage
Cohort Studies
Cross-Over Studies
Dose-Response Relationship, Drug
Drug Overdose/epidemiology
England/epidemiology
Female
Humans
Male
Middle Aged
Practice Patterns, Physicians'/statistics & numerical data
Psychotropic Drugs/administration & dosage
Risk
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bja.2021.06.049

Cite this

@article{09700c16cfec44ca89f45b01f7703233,

title = "Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover study",

abstract = "BACKGROUND: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care.METHODS: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows.RESULTS: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06-4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01-5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02-9.04) significantly increased the risk of ORD.CONCLUSIONS: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day-1 and the combination of opioids and gabapentinoids, even with low opioid doses.",

keywords = "Adult, Aged, Aged, 80 and over, Analgesics, Opioid/administration & dosage, Cohort Studies, Cross-Over Studies, Dose-Response Relationship, Drug, Drug Overdose/epidemiology, England/epidemiology, Female, Humans, Male, Middle Aged, Practice Patterns, Physicians'/statistics & numerical data, Psychotropic Drugs/administration & dosage, Risk, Young Adult",

author = "Teng-Chou Chen and Knaggs, {Roger D} and Li-Chia Chen",

note = "Funding Information: T-CC received a PhD studentship awarded by the University of Nottingham for the submitted work. T-CC reported grants from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East Midlands, International Society for Pharmacoepidemiology, and European Pain Federation, outside of the submitted work. RDK reported funding for a PhD studentship unrelated to this work from Mundipharma Research Ltd; is a member of the Advisory Council on the Misuse of Drugs, National Institute for Health and Care Excellence Chronic Pain Guideline Committee; and is the current Vice President of the British Pain Society. L-CC received funding from a pharmaceutical company, Mundipharma Research Ltd, for a post-marketing pharmacovigilance study unrelated to this work, and T-CC was employed on this grant. Funding Information: T-CC received a PhD studentship awarded by the University of Nottingham for the submitted work. T-CC reported grants from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East Midlands, International Society for Pharmacoepidemiology, and European Pain Federation , outside of the submitted work. RDK reported funding for a PhD studentship unrelated to this work from Mundipharma Research Ltd ; is a member of the Advisory Council on the Misuse of Drugs, National Institute for Health and Care Excellence Chronic Pain Guideline Committee; and is the current Vice President of the British Pain Society. L-CC received funding from a pharmaceutical company, Mundipharma Research Ltd , for a post-marketing pharmacovigilance study unrelated to this work, and T-CC was employed on this grant. Publisher Copyright: {\textcopyright} 2021 British Journal of Anaesthesia",

year = "2021",

month = nov,

doi = "10.1016/j.bja.2021.06.049",

language = "English",

volume = "127",

pages = "789--797",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "Elsevier BV",

number = "5",

}

TY - JOUR

T1 - Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England

T2 - a case-crossover study

AU - Chen, Teng-Chou

AU - Knaggs, Roger D

AU - Chen, Li-Chia

N1 - Funding Information: T-CC received a PhD studentship awarded by the University of Nottingham for the submitted work. T-CC reported grants from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East Midlands, International Society for Pharmacoepidemiology, and European Pain Federation, outside of the submitted work. RDK reported funding for a PhD studentship unrelated to this work from Mundipharma Research Ltd; is a member of the Advisory Council on the Misuse of Drugs, National Institute for Health and Care Excellence Chronic Pain Guideline Committee; and is the current Vice President of the British Pain Society. L-CC received funding from a pharmaceutical company, Mundipharma Research Ltd, for a post-marketing pharmacovigilance study unrelated to this work, and T-CC was employed on this grant. Funding Information: T-CC received a PhD studentship awarded by the University of Nottingham for the submitted work. T-CC reported grants from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East Midlands, International Society for Pharmacoepidemiology, and European Pain Federation , outside of the submitted work. RDK reported funding for a PhD studentship unrelated to this work from Mundipharma Research Ltd ; is a member of the Advisory Council on the Misuse of Drugs, National Institute for Health and Care Excellence Chronic Pain Guideline Committee; and is the current Vice President of the British Pain Society. L-CC received funding from a pharmaceutical company, Mundipharma Research Ltd , for a post-marketing pharmacovigilance study unrelated to this work, and T-CC was employed on this grant. Publisher Copyright: © 2021 British Journal of Anaesthesia

PY - 2021/11

Y1 - 2021/11

N2 - BACKGROUND: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care.METHODS: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows.RESULTS: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06-4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01-5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02-9.04) significantly increased the risk of ORD.CONCLUSIONS: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day-1 and the combination of opioids and gabapentinoids, even with low opioid doses.

AB - BACKGROUND: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care.METHODS: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows.RESULTS: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06-4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01-5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02-9.04) significantly increased the risk of ORD.CONCLUSIONS: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day-1 and the combination of opioids and gabapentinoids, even with low opioid doses.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Analgesics, Opioid/administration & dosage

KW - Cohort Studies

KW - Cross-Over Studies

KW - Dose-Response Relationship, Drug

KW - Drug Overdose/epidemiology

KW - England/epidemiology

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Practice Patterns, Physicians'/statistics & numerical data

KW - Psychotropic Drugs/administration & dosage

KW - Risk

KW - Young Adult

U2 - 10.1016/j.bja.2021.06.049

DO - 10.1016/j.bja.2021.06.049

M3 - Article

C2 - 34419240

SN - 0007-0912

VL - 127

SP - 789

EP - 797

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 5

ER -

Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover study

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this