The Effect of Opioid Analgesics, Benzodiazepines, Gabapentinoids, and Opioid Agonist Treatment On Mortality Risk Among Opioid-Dependent People

Author: Chrianna Bharat Natasa Gisev Sebastiano Barbieri Timothy Dobbins Sarah Larney Michael Farrell Louisa Degenhardt

Theme: Epidemiology & Public Health Research Year: 2022

As dispensings for benzodiazepines and gabapentinoids have increased in recent years, risk of
increased mortality has been identified, particularly when used with opioids. There is limited
research examining use of these medicines among people with opioid dependence and whether
mortality risk varies according to opioid agonist treatment (OAT) status. This study characterizes
patterns of opioid analgesic utilization and concomitant use of benzodiazepines, gabapentinoids and
OAT among people with opioid dependence initiating opioid analgesics. It also assesses mortality risk
associated with exposure to these medicines.
Retrospective cohort study in New South Wales, Australia, including 28,891 people with
documented opioid dependence initiating opioid analgesics between July 2003 and December 2018.
Linked administrative records provided data on prescription dispensings, sociodemographics, clinical
characteristics, OAT and mortality. Generalised estimating equation models estimated incidence rate
ratios (IRR) comparing periods in and out of OAT for the number of opioid analgesic dispensings.
Periods of concomitant use of opioid analgesics, benzodiazepines, gabapentinoids, and OAT were
identified. Cox models assessed associations between concomitant medicines use with mortality
At the time of opioid analgesic initiation, 43.7% of the cohort were in OAT. The most commonly
initiated opioid was codeine (67.8%). In the 90 days prior to the index opioid dispensing,
benzodiazepines were more frequently dispensed than gabapentinoids, but rates varied over time.
Between 2004 and 2018, benzodiazepine dispensings decreased (41.7% to 21.1%) while
gabapentinoid dispensings increased (0.2% to 7.9%). Incidence of opioid analgesic dispensings was
higher during periods out of OAT compared to in OAT (5.8 v. 2.3 per person-year; IRR 0.39, 95% CI
0.38, 0.41). Analyses investigating associations between medicine exposure and mortality are
People with opioid dependence had high rates of recent benzodiazepine utilization and current OAT
enrollment at the time of opioid analgesic initiation. OAT was associated with a significant reduction
in opioid analgesic prescribing.
Disclosure of Interest Statement:
S.L. has received untied education funding from Indivior. L.D. has received untied educational funding
from Reckitt Benckiser, Indivior, Mundipharma Pty Ltd, and Seqirus. These untied grants are all
unrelated to the current study. All other authors declare no competing interests.

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