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INNOSC Theranostics and
Pharmacological Sciences Benzodiazepine use and retention in OAT

OAT has demonstrated effectiveness in supporting long- drug poisoning from BZDs when combined with MOUD
term abstinence, aiding in rehabilitation, and lowering the and potential concurrent use of either licit or illicit opioids.
risk of overdosing and relapse. 10,16,17
Polysubstance use, both prescription and illicit, is 2. Methods
extremely common during OAT. 18-21 The concurrent use of 2.1. Search strategy
MOUD with benzodiazepines (BZDs) has raised concerns When selecting the articles for this review, the authors
due to its high potential for abuse and dependence. started by making a comprehensive selection of terms
18
BZDs are a class of anticonvulsant/anxiolytic drugs that that could be used to describe opioids, OAT, BZDs, and
are prescribed to treat insomnia, anxiety, depression, treatment retention. These terms were chosen with the
muscle spasms, panic attacks and seizure disorders, help of a university librarian and by looking through
many of which are common opioid withdrawal articles in PubMed and Google Scholar to see what terms
symptoms. 22,23 When BZDs are taken alone, overdose risk were commonly used. For the final analysis, studies were
is minimal. However, when taken alongside MOUD, searched for that reported the effect of concurrent BZD
24
both drugs act synergistically to enhance GABA receptor and MOUD on treatment retention in OAT. EMBASE,
function, significantly increasing the risk of respiratory PubMed, and Google Scholar (Ovid) were searched for
depression, opioid-related overdose and other substance- studies from inception until January 30, 2024. The search
related overdose, hospitalization and death. 24-27 It has strategy used keywords that described opioids, BZDs,
been reported that the mortality rate for concurrent OATs, and treatment retention (Table 1).
administration of both medications is ten times higher Keywords included plural options whenever possible
than those taking only opioids. The risk of respiratory and were adapted to the requirements of the database.
28
depression, overdose and death can be exacerbated due to Additional studies were identified by searching the
the prevalence of illicit BZDs laced with synthetic opioids. reference list of relevant publications and by using
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As such, BZD use is often present in opioid overdoses, EMBASE, PubMed, and Google Scholar, as previously. 33,34
with one recent study identifying BZD use in 80% of fatal There were no limitations placed on language, year, age,
opioid overdoses. Despite the increased overdose risk sex, ethnicity, research location, or trial length during the
30
with BZD, they are often prescribed alongside OAT. literature search, but only studies in English were included.
31
Current recommendations are for short-term BZD use, A study was included if it: involved both BZD and one of
however, many patients consume BZDs illicitly, where the the MOUDs (methadone, buprenorphine, or naltrexone
dose, frequency, and duration of BZD use are not defined adherence) and treatment retention as one of the primary
or regulated. In the face of increasing concerns over BZD or secondary outcomes. All literature must have been
31
use in OAT, the US Food and Drug Administration has published in a peer-reviewed journal. It is worth noting
stated that patients should not be turned away from OAT that in the title and abstract search, many of the articles
if they have a history of BZD use or are currently using lacked the treatment retention aspect of our search criteria.
BZD. 32 This was in part because the database matched a part of
Currently, the association between concurrent BZD the terms that we included: “drug” in “drug adherence” or
and MOUD use and increased overdose risk is well
established. 14,15,26 However, the association between BZD
use and retention in OAT programs remains less well Table 1. Search terms for literature review
known. This literature review therefore aims to evaluate Major category Search terms
how the concurrent use of BZD and MOUD specifically Benzodiazepine Benzodiazepine(s), benzodiazepine dependence
influences treatment retention in OAT programs, which is Opioids Opioid(s), opioid/opiate agonist, medication for
an important part of recovery. In this review, we explore opioid use disorder(s), MOUD(s), buprenorphine(s),
the impact of important variables in BZD use, including buprenorphine plus naloxone, methadone(s),
the prevalence of BZD use in the MOUD-using population, naltrexone(s)
as well as BZD use at intake into the treatment program, Opioid agonist Treatment for opioid use disorder, opioid agonist
licit versus illicit BZD use, frequency of BZD use, and treatment treatment(s), buprenorphine treatment(s),
where BZD prescribed use was considered as a variable in methadone treatment(s), methadone maintenance
treatment outcomes. treatment(s), medication assisted treatment(s),
OAT(s), MAT(s), MMT(s)
We note however, a priori, that it is important to Treatment Treatment retention, treatment response(s), program
consider that any such benefits from improved treatment retention retention(s), drug adherence(s), medication
retention must be balanced against a possible greater risk of compliance(s)

Volume 8 Issue 3 (2025) 22 doi: 10.36922/itps.5151