Journal of Addictive Diseases

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/wjad20

Drug type and risk behaviors associated with non-

fatal overdose among people who use drugs: a
systematic review and meta-analysis

Bahram Armoon, Neda SoleimanvandiAzar, Mohammad Rostami, Peter

Higgs, Azadeh Bayani, Amir-Hossein Bayat, Rasool Mohammadi, Elahe
Ahounbar & Ladan Fattah Moghaddam

To cite this article: Bahram Armoon, Neda SoleimanvandiAzar, Mohammad Rostami, Peter
Higgs, Azadeh Bayani, Amir-Hossein Bayat, Rasool Mohammadi, Elahe Ahounbar & Ladan
Fattah Moghaddam (2022) Drug type and risk behaviors associated with non-fatal overdose
among people who use drugs: a systematic review and meta-analysis, Journal of Addictive
Diseases, 40:1, 114-125, DOI: 10.1080/10550887.2021.1950262

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Journal of Addictive Diseases
2022, VOL. 40, NO. 1, 114–125
https://doi.org/10.1080/10550887.2021.1950262

Drug type and risk behaviors associated with non-fatal overdose among
people who use drugs: a systematic review and meta-analysis
Bahram Armoon, PhDa,b , Neda SoleimanvandiAzar, PhDc, Mohammad Rostami, PhDd, Peter
Higgs, PhDe, Azadeh Bayani, MScf, Amir-Hossein Bayat, PhD f, Rasool Mohammadi, PhDg, Elahe
Ahounbar, Msch and Ladan Fattah Moghaddam, Msc
a
Douglas Hospital Research Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; bDepartment of Psychiatry,
McGill University, Montreal, QC, Canada; cPreventive Medicine and Public Health Research Center, Psychosocial Health Research
Institute, Iran University of Medical Sciences, Tehran, Iran; dDepartment of Counseling, Faculty of Humanities and Social Sciences,
University of Kurdistan, Kurdistan, Iran; eDepartment of Public Health, School of Psychology and Public Health, La Trobe University,
Melbourne, VIC, Australia; fSocial Determinants of Health Research Center, Saveh University of Medical Sciences, Saveh, Iran;
g
Department of Biostatistics and Epidemiology, School of Public Health and Nutrition, Lorestan University of Medical Sciences,
Khorramabad, Iran; hSubstance Abuse and Dependence Research Center, The University of Social Welfare and Rehabilitation Sciences,
Tehran, Iran; iDepartment of Nursing, Faculty of Nursing and Midwifery, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

ABSTRACT KEYWORDS
The present study aimed to determine the association between drug type, risk behaviors Non-fatal overdose;
and non-fatal overdose among people who use drugs (PWUD). We searched for studies in crystal methamphetamine use;
English published before February 1, 2021, on PubMed, Scopus, Cochrane, and Web of heroin injection;
Science to identify primary studies on the factors associated with non-fatal overdose among cocaine use
PWUD. After reviewing for study duplicates, the full-text of selected articles were assessed
for eligibility using Population, Intervention, Comparator, Outcomes (PICO) criteria. After a
detailed assessment of over 13,845 articles, a total of 49 studies met the eligibility criteria.
We found that non-injection opioid use, heroin injection, cocaine use, concurrent use of
buprenorphine and benzodiazepines, benzodiazepine use, incarceration, injecting drugs, and
duration of injecting were associated with greater odds of non-fatal overdose among PWUD.
The findings of the current meta-analysis support the requirement to improve suitable harm
reduction strategies for drug users, such as peer-based overdose management, and further
focusing on the need to balance the current emphasis on enforcement-based responses to
illegal drug use with health-related interventions.

Background have been found to reduce overdose mortality in

Understanding the use of different types of drugs,
either prescribed or illicit, is important for iden-
tifying risk factors in overdose mortality.1,2 It is
well documented that combined use of opioids
and other substances, particularly alcohol and ben-
zodiazepines, increase the chances of an overdose.3
Epidemiological research shows that most of the
risk factors for overdose are based in both
social-structural exposures as well as individual-level
behaviors, for instance, types of drugs and method
of consumption, public injecting, housing instabil-
ity, law enforcement and incarceration.4 Structured
interventions like supervised injection facilities
some settings.5
Our review of the literature shows that there
is less attention paid to non-fatal overdoses.
However, the factors related to non-fatal over-
dose might differ from ones that increase the
likelihood of fatal overdose. The evidence that
does exist describes the factors associated with
experiencing a non-fatal opioid overdose as
including poly-substance use (especially concur-
rent use of opioids and benzodiazepines and/or
cocaine), injection as the route of administra-
tion, unstable housing, criminal history, and
reporting a recent history of overdose.6 In their

CONTACT Bahram Armoon, PhD Bahramarmun@gmail.com Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, QC H4H
1R3, Canada.
© 2021 Taylor & Francis Group, LLC

clinical population from St. Petersburg, Walley
and colleagues found 16% of people living with
HIV who were both injecting drugs and heavy
alcohol consumers reported a previous non-fatal
overdose.7 Higher overdose rates are known to
be associated with concomitant alcohol use
among people also injecting other drugs8,9 and
may represent behavioral or pharmacological
interactions.10 The risk of overdose is greater
for example, when heroin users inject concur-
rently with other sedatives or alcohol11–13 and
those who report a previous non-fatal overdose
are more likely to experience another in the
future.13
Pharmacologically, neural depressants, such as
alcohol or benzodiazepines, can interact syner-
gistically with opioids to suppress the respiratory
system, resulting in overdose.8,14–17 However, bio-
logical risks are also influenced by the social
context of drug use.18,19 Drug use in periods of
reduced individual tolerance is well understood
to increase the risk of overdose.20 This risk is
pronounced when individuals undergo periods of
forced abstinence during incarceration or detox-
ification and are released without medication-
assisted therapy.21,22 Additionally, law enforcement
practices can influence individual injection behav-
iors, potentially facilitating drug use in situations
that decrease the risk of police detection but
increase the risk of overdose.8,23–25 A variety of
factors, including poverty, unstable housing, and
current drug policies, contribute to risk environ-
ments26 that increase the probability that people
inject in unsafe public places that raise suscep-
tibility to drug-related harms. These specific con-
ditions increase the risk of drug-related adverse
effects, for instance, infectious disease and
overdose.27–32
There is one meta-analysis that investigated
the prevalence of non-fatal overdose among peo-
ple who inject drug users33 which did not con-
sider the risk factors, therefore it is essential to
improve our knowledge about any associated risk
factors to inform overdose prevention and assis-
tance programs. The aim of the present study
was to determine associations between drug type,
risk behaviors and non-fatal overdose among peo-
ple who use drugs.
Journal of Addictive Diseases 115
Methods
Search strategy and study selection
This systematic review and meta-analysis study
has been conducted based on the instructions in
Protocols of Systematic Reviews and Meta-Analyses
(PRISMA).34,35 The process of the current study
selection is demonstrated in Figure 1.
The search strategy, included studies published
from January 1, 1995 to February 1, 2021 were
retrieved and incorporated additional papers from
the reference lists. In the study selection phase,
two independent researchers (AB and BA) sepa-
rately reviewed the papers obtained from the
databases of PubMed, Scopus, Web of Science,
and Cochrane separately.
Only English language papers were included
in the study, and also, the limitations such as
time and geographic items were considered.
Papers were reviewed twice based on the abstract
and the relevance to the subject.
Inclusion criteria based on PICOS
Population: People who use drugs (PWUD)
Intervention: Crystal methamphetamine use,
non-injection opioid use, heroin injection, cocaine
use, concurrent use of buprenorphine and ben-
zodiazepines, benzodiazepines use, incarceration,
types of drugs injected, and duration of injecting.
The Comparison Group: PWUD not reporting
overdose in the last year.
Outcomes: Non-fatal overdose in the last year.
Study design: Cross-sectional, cohort, and
case-control studies were included.
All qualitative studies, secondary studies, sys-
tematic reviews and, meta-analysis studies, and
papers not published in English were excluded
from the present study.
Data extraction and study quality assessment
Two researchers (AB and BA) reviewed and assessed
the papers independently, applying a standardized
data gathering form. Any lack of consensus between
the two researchers was resolved through consul-
tation from two other members of the research
team (EA and RM). Microsoft Excel software was
116 B. ARMOON ET AL.
Figure 1.  PRISMA flow diagram.
used for data extraction and management. Two
separate reviewers (authors BA and AB) chose the
papers in a two-phase monitoring process. In the
first step, the duplicated titles/abstracts (89% agree-
ment) according to the criteria one through three
mentioned below were deleted. In the second phase,
titles/abstracts were selected for full-text review
based on the inclusion criteria (96% agreement).
The data were gathered from selected papers,
recording the surname of the first author, pub-
lication date, crystal methamphetamine use,
non-injecting opioid use, heroin injection, cocaine
use, buprenorphine use, benzodiazepines use,
incarceration, drug type injected, and duration
of injecting. To assess the quality of the reviewed
papers, the Newcastle-Ottawa Scale (NOS)36 was
applied.
To assess the quality of included studies, a
modified version of NOS was used to evaluate
statistical quality, sample representativeness, and
sample size. The comparability between people
was the area that was applied for the NOS when
evaluating the quality of individual studies. A
maximum of five quality scores were defined for

items. Publications with a total score of 0–2, 3,
4, and 5 points were recorded as “unsatisfactory,”
“satisfactory,” “good,” or “very good,” respectively.
The agreement beyond chance (unweighted
kappa) was applied to assess the consensus
between the two authors (BA and AB) during
the quality evaluation. The levels of poor, slight,
fair, moderate, substantial, and almost perfect
levels of agreement were considered by the values
0, 01–0.02, 0.021–0.04, 0.041–0.06, 0.061–0.08,
and 0.081–1.00, respectively.37
Data synthesis and statistical analysis
The current meta-analysis study was conducted
by producing pooled odds ratios (OR) and the
95% confidence intervals on identifying factors
associated to non-fatal overdose. The OR was
computed using a 2 × 2 table, and OR < 1 as a
positive association between non-fatal overdose
and the target variable was considered. An OR
> 1 (as the statistical threshold for assessing the
association between outcome variables and expos-
itive variables) represent a strong association
between variables and vice versa. To evaluate the
lack of correlation between studies, the Q test
with a P value < 0.05 and I2 statistics with a
cutoff of ≥50% were the best options. The con-
fidence intervals of 95% were considered for I2,
where the negative values were assumed as zero.
The random-effects model was applied to achieve
the pooled estimation, considering the various
sampling methods of the studies. To identify any
publication bias, the Begg’s and Egger’s publica-
tion bias approach were used both in graphical
and statistical dimensions.38,39P-values of less than
0.05 were considered significant. The association
between high-risk behaviors was demonstrated
by an OR and 95% CI, and the results were
showed in forest plots. For data analysis, R 3.5.1
with the “meta” package was used to conduct the
meta-analysis.
Results
Study characteristics
After careful evaluations of the extracted cita-
tions, 49 studies were included.6,8,14,40–85 Selected
Journal of Addictive Diseases 117
studies were from six WHO regions (32 from
Region of the Americas [n = 3, with 981,138 par-
ticipants], six from the European Region [n = 15,
with 284 participants], one from South-East Asia
Region [with 252 participants], eight from the
Western Pacific Region [n = 4, with 649 partici-
pants], one from the Eastern Mediterranean
Region [with 465 participants] and one from the
African Region [with 200 participants]. The USA
had the highest number of reports (22 studies,
including 3,948,086 participants). Considering
country income level, 40 studies (with 3,997,239
participants) were conducted within high-income
countries, six studies (with 3,047 participants)
within upper-middle-income countries and three
studies were (including 1,702 participants) were
from a lower middle-income country.
Results of the meta-analysis
In Table 1, the key characteristics of the included
studies for the drug type risk behaviors associated
with non-fatal overdose among PWUD are pre-
sented (Table 1).
The association can be inferred through Table 2.
Drug type associated with non-fatal overdose
As illustrated in Table 2, there was no significant
association found between crystal methamphet-
amine use and non-fatal overdose among PWUD
(OR = 1.78, 95%CI = 0.79–4.03).
Table 2 indicates the association between injec-
tion and non-injection opioid use and non-fatal
overdose among PWUD. Our findings show peo-
ple reporting opiate use were 1.86 times more
likely to report having had a non-fatal overdose
during last year (OR = 1.86, 95%CI = 1.50–2.31).
Table 2 indicates the association between her-
oin injection and non-fatal overdose among
PWUD. Our findings show people who report
heroin injecting are 2.39 times more likely to
report having had a non-fatal overdose during
the past year (OR = 2.39, 95%CI = 1.58–3.63).
Table 2 shows the positive relationship between
cocaine use and non-fatal overdose among
PWUD. Participants who used cocaine were 1.80
times more likely to report having a non-fatal
overdose in the last 12 months (OR = 1.80, 95%CI
= 1.58–2.05).
118 B. ARMOON ET AL.

Table 1. Characteristics of non-fatal overdose among PWUD.

Author Participants Sample size Year Country Study design
Fairbairn et  al.52 IDU 551 2008 Canada Cohort
O’Halloran et  al.68 IDU 3850 2018 Ireland Cross-section
Pizzicato et  al.6 DU 370 2019 USA Cross-section
Fairgrieve et  al.53 IDU 889 2019 Canada Cross-section
Smolina et  al.78 DU 8831 2020 Canada Cohort
Cheng et  al.45 DU 599 2020 Canada Cross-section
Fischer et  al.54 DU 679 2004 Canada Cross-section
Milloy et  al.65 IDU 252 2010 Thailand Cohort
Uusküla et  al.80 IDU 588 2015 Russia and Estonia Cross-section
Mateu-Gelabert et  al.63 DU 353 2020 USA Cross-section
Seal et  al.76 IDU 1427 2001 USA Cross-section
Bergenstrom et  al.40 IDU 299 2008 Vietnam Cross-section
Brugal et  al.14 DU 2556 2001 Spain case-control
Burke et  al.43 DU 2154426 2019 USA Cohort
Chahua et  al.44 DU 452 2012 Spain Cross-section
Coffin et  al.47 IDU 772 2007 USA Cross-section
Darke and Ross.48 IDU 312 1997 Australia Cross-section
Darke et  al.49 DU 495 2005 Australia Cross-section
Dilokthornsakul et  al.50 DU 816 2016 USA Cross-section
Escudero et  al.51 IDU 15070 2016 Canada Cross-section
Galea et  al.55 DU 1066 2008 USA Cross-section
Hakansson et  al.57 DU 7085 2008 Sweden Cross-section
Hunter et  al.58 IDU 283 2018 USA Cross-section
Kilaru et  al.60 DU 6451 2020 USA Cohort
Kerr et  al.59 IDU 1587 2007 Canada Cross-section
Lagu et  al.61 DU 329 2005 USA Cross-section
Lake et  al.62 IDU 1660 2015 Canada Cross-section
McGregor et  al.64 DU 218 1998 Australia Cross-section
Nam et  al.66 DU 246466 2020 USA Cohort
Sherman et  al.77 IDU 309 2008 USA Cross-section
Britton et  al.42 DU 3900 2010 USA Cross-section
Kinner et  al.8 DU 2515 2012 Canada Cohort
Rowe et  al.73 DU 172 2016 USA Cross-section
Yule et  al.84 DU 200 2018 USA Cross-section
Yule et  al.83 DU 127 2019 USA Cross-section
Cochran et  al.46 DU 382828 2019 USA Cross-section
Ochoa et  al.69 IDU 759 2005 USA Cross-section
Zhou et  al.85 IDU 340 2016 china Cross-section
Groenewald et  al.56 DU 1146412 2019 USA Cohort
Rafful et  al.71 IDU 671 2018 Mexico Cross-section
Riley et  al.72 IDU 173 2016 USA Cohort
Blackburn et  al.41 IDU 1203 2017 Vietnam Cross-section
Park et  al.70 IDU 203 2018 USA Cross-section
Noroozi et  al.67 IDU 465 2020 Iran Cross-section
Saleem et  al.74 DU 200 2021 Tanzania Cross-section
Schiavon et  al.75 DU 244 2018 USA Cross-section
Stewart et  al.79 DU 753 2002 England Cross-section
Winter et  al.81 IDU 1051 2015 Australia Cross-section
Yin et  al.82 DU 731 2007 china Cross-section

Another finding from our data was concurrent Risk factors for non-fatal overdose
use of buprenorphine and benzodiazepines had
Table 2 indicates the association between incar-
a positive association with non-fatal overdose
ceration and non-fatal overdose among PWUD.
among PWUD. PWUD who used buprenorphine
Our findings show PWUD who had experienced
were 2.87 times more likely to have non-fatal
incarceration were 1.79 times more likely to
overdose (last 12 months) (OR = 2.87, 95%CI =
report having had non-fatal overdose during last
1.71–4.80) (Table 2).
year (OR = 1.79, 95%CI = 1.43–2.23).
Additionally, Table 2 indicates a significant
Table 2 indicates the association between
correlation between benzodiazepines use and
injecting drugs and non-fatal overdose among
non-fatal overdose among PWUD with people
PWUD. Our findings show people who reported
who report using benzodiazepines being 1.64
injecting were 2.94 times more likely to report
times more likely to have had non-fatal overdose
having had a non-fatal overdose during last year
in the previous 12 months than those who did
(OR = 2.94, 95%CI = 2.16–4.01)
not use (OR = 1.64, 95%CI = 1.34–2.02).
 Journal of Addictive Diseases 119

Table 2.  Pooled odds ratio of variables associated with non-fatal overdose among PWUD.
Number Degrees of
Variables Model study ORs, 95%CI freedom P* I2
Crystal methamphetamine use Random 4 1.78, 95% CI (0.79–4.03) 3.00 0.01 0.85
Injection and non-injection opioid use Random 10 1.86, 95% CI (1.50–2.31) 9.00 0.01 0.83
Heroin injection Random 17 2.39, 95% CI (1.58–3.63) 16.00 0.01 0.99
Cocaine use Random 7 1.80, 95% CI (1.58–2.05) 6.00 0.26 0.23
Concurrent use of buprenorphine and benzodiazepines Random 5 2.87, 95% CI (1.71–4.80) 4.00 0.01 0.75
Benzodiazepines use Random 12 1.64, 95% CI (1.34–2.02) 11.00 0.01 0.96
Incarceration Random 10 1.79, 95% CI (1.43–2.23) 9.00 0.01 0.76
Injected drugs Random 10 2.94, 95% CI (2.16–4.01) 9.00 0.01 0.65
Duration of injecting Random 7 1.33, 95% CI (1.15–1.53) 6.00 0.01 0.87
*P related to heterogeneity statistic.

Our data show that the duration of injecting
had a positive association with non-fatal overdose
among PWUD where people with long duration
(>10 years) of injecting were 1.33 times more
likely to have non-fatal overdose (last 12 months)
(OR = 1.33, 95%CI = 1.15–1.53) (Table 2).
To identify the probable publication bias, the
Egger’s test and the graph were performed.
Considering the symmetry assumption, there were
no significant publication bias observed in the
reviewed studies selected for inclusion. As regards
the funnel plot, the distribution of the articles
was not oriented, and for most of them, it was
identical, confirming no publication biases in our
study. The publication bias test indicates consid-
erable bias based on Eggers test (coefficient =
3.66, P-value < 0.001).
Discussion
This study assessed the types of drug used and
behavioral risk factors associated with non-fatal
overdose among PWUD.
We found that non-injection opioid use, heroin
injection, cocaine use, buprenorphine use benzo-
diazepine use, incarceration, injecting drugs, and
duration of injecting were all associated with
greater odds of non-fatal overdose among PWUD.
An association was also observed between recent
incarceration and overdose, i.e., in line with pre-
vious studies revealing that the use of substances
in prison often less than used in the community
leading to a decreased tolerance for
recently-released individuals.14
Cocaine and opiates use were associated with
non-fatal overdose. T Previous research has found
a correlation between non-fatal overdose and opi-
oids and stimulants co-use in individuals under-
going mental health issues.86 Addressing any
independent associations between injecting
cocaine and experiencing an overdose might be
more difficult because of the lack of attention to
cocaine-induced overdose in PWUD.87 However,
this is not surprising data with respect to the
prevalence of injecting cocaine in some local
populations of PWUD (e.g. Vancouver, Canada)
where the purity of locally-obtained cocaine has
been reported as high.88
Evidence exists for an elevated risk for non-fatal
overdose among PWUD with a longer history of
injection (i.e., 6–7 years past initiation). The con-
sequences of declining rates might fail to present
actual decreased threats; but instead indicate a
survivor impact in the longer-term drug injectors.
These data were in line with those studies con-
ducted in Australia64 and Britain,12 suggesting
higher risks for more-experienced PWUD, when
compared to those with a more recent injec-
tion onset.
Our study found an independent correlation
between overdose, a history of injecting drugs,
and the illicit use of buprenorphine/benzodiaze-
pine use. There exists a possibility of discordant
time-induced reverse causality between these
characteristics; however, the use of diverted
buprenorphine/benzodiazepines has been reported
previously.89 Accordingly, such a relationship has
been reported previously90 highlighting the cor-
relation between recent (last month) non-fatal
overdose and the illicit use of these substances.
Some suggestions for buprenorphine/benzodiaz-
epines diversion, have been documented includ-
ing to help control opioid withdrawal symptoms,
the unaffordability of treatment and the lack of
access to treatment services despite the desire.91–93
Primary health services providing care to PWUD
can help reduce overdose94 and in the sterile
syringe programs for PWUD have also been
120 B. ARMOON ET AL.
found to encourage treatment for people with
limited or no access to buprenorphine/
benzodiazepines.95
Our data on the association between length of
drug injection and increased risks for overdose
were consistent with those of previous investiga-
tions.15,96,97 Not surprisingly given the physiological
impact of heroin pharmacology98 we found a
higher rate of self-reported overdose in those with
a history of injecting heroin in the past 12 months,
compared to those without such experiences.
Limitations and strengths of the study
Limitations to the study include a lack of con-
sistency in the definition of non-fatal overdose
and the reliance on participant self-report.
Second, most of the selected studies were
cross-sectional meaning causal and temporal
associations between risk behavior and non-fatal
overdose are not possible. However, the current
study may improve the statistical conclusion of
analyses and increase the reliability of the evi-
dence. 99 Third, the high comorbidity/overlap
between diagnosed mental health disorders and
drug use disorders including mood disorders,
anxiety disorders, personality disorders might be
cofounding factors. In addition, since we had no
intervention with the setting of independent and
dependent variables, we had to rely on the data
that were published in the articles.100,101
One of the advantages of this meta-analysis
was the impressive separate approximation of the
correlation between high-risk behavior and
non-fatal overdose. We also conducted a com-
prehensive and precise search strategy and
reviewed a considerable number of databases to
enhance the sensitivity of the search to consider
all the potential studies. In addition, every obser-
vational study was assessed, regardless of age,
location, date of publication, and language. In
total 13,845 papers were included for review and
49 eligible studies, were subsequently included in
the meta-analysis.
Conclusions
The present study shows a significant proportion
of participants reported non-fatal overdose. The
findings of the current meta-analysis support the
requirement to improve the development of inter-
ventions for people who use drugs (especially
those who report injecting for longer periods of
time). This may include both individually focused
peer based programs and more structural inter-
ventions including drug law reform.
Abbreviations
CI Confidence intervals
NOS Newcastle-Ottawa scale
OR Odds ratio
PICO Population, intervention, comparator, outcomes
PRISMA Protocols of systematic reviews and
meta-analyses
PWID People who inject drugs
PWUD People who use drugs
WHO World Health Organization
Acknowledgments
This study was sponsored by Social Determinants of Health
Research Center, Saveh University of Medical Sciences,
Saveh, Iran.
Author contributions
AB and BA. Conceived the study EA and BA collected all
data. AB, AHB, LFM and EA analyzed and interpreted the
data. RM, PH, NSA, MR and BA drafted the manuscript.
All authors commented on the drafts of the manuscript
and approved the final copy of the paper for submission.
Availability of data and materials
The datasets used and/or analyzed during the current study
are available from the corresponding author on reasonable
request.
Declaration of interest statement
The authors declare that there are no conflicts of interest.
Ethics approval and consent to participate
This study was an analysis of preexisting literature and did
not use human subjects.
ORCID
Bahram Armoon http://orcid.org/0000-0001-5467-9889

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