Characteristics of Opioid-Users Whose Death Was
Related to Opioid-Toxicity: A Population-Based Study in
Parvaz Madadi1*, Doris Hildebrandt2, Albert E. Lauwers2, Gideon Koren1
1Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada, 2The Office of the Chief Coroner of
Ontario, Toronto, Ontario, Canada
Background: The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in
opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose
cause of death was related to opioid toxicity.
Methods: This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which
occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were
identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative,
and quantitative variables were extracted, tabulated, and analyzed.
Results: Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n=1359).
Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used
opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation,
chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the
time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in
methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental
illness, previous suicide attempts, chronic pain, and a history of cancer.
Significance/Conclusion: These results identify novel, susceptible groups of opioid-users whose cause of death was related
to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion
amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on
subpopulations of opioid users.
Citation: Madadi P, Hildebrandt D, Lauwers AE, Koren G (2013) Characteristics of Opioid-Users Whose Death Was Related to Opioid-Toxicity: A Population-Based
Study in Ontario, Canada. PLoS ONE 8(4): e60600. doi:10.1371/journal.pone.0060600
Editor: Sam Eldabe, The James Cook University Hospital, United Kingdom
Received December 3, 2012; Accepted February 28, 2013; Published April 5, 2013
Copyright: ? 2013 Madadi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: PM is the recipient of a Postdoctoral Fellowship from the Canadian Institutes for Health Research and has also received Postdoctoral funding from the
Canadian Pain Society, the Canadian Pharmacogenomics Network for Drug Safety, and the Quebec Training Network in Perinatal Research. Dr. Koren is the holder
of the Ivey Chair in Molecular Toxicology at Western University. The funders had no role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: email@example.com
Non-medical use of prescription opioids has culminated in a
public health crisis in many North American jurisdictions. The
impact of this crisis has been powerfully illustrated by the dramatic
increase in opioid-related deaths [1–6]: in 2008, prescription
opioids were involved in 14,800 accidental deaths in the United
States . That there has been a parallel increase in the
consumption of prescription opioids and deaths related to opioid
drugs is not in dispute. Previous studies of Ontarians whose cause
of death was related to opioids have deduced several relationships
between opioid prescription practices and opioid-related deaths.
Firstly, the introduction of long-acting oxycodone to the provincial
formulary has been singled out as an important contributor to the
increase in opioid-related morality in this province . Secondly,
regions/municipalities within the province with a high incidence
of opioid-related deaths per capita have high opioid prescription
utilization . Thirdly, opioid-related deaths appear to be
concentrated amongst patients treated by physicians who
prescribed opioids more frequently , and high doses are
significantly associated with an increase risk of mortality . Such
discoveries have subsequently shaped new provincial strategies to
help curb and prevent this epidemic [10–12].
However, we need more individualized evidence and insight on
how and why opioid-related deaths occur in order to develop
holistic, inclusive, and multifaceted preventative strategies towards
this issue. For example, indicators of opioid diversion and misuse
amongst those whose cause of death was opioid-related in Canada
has not been evaluated, despite data illustrating the enormity of
these considerations in the United States [13,14]. We aimed to
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identify patterns and characteristics amongst opioid-users whose
cause of death was related to opioid toxicity in the province of
Ontario between the years 2006 and 2008.
This study was approved by the Office of the Chief Coroner of
Ontario and the Research Ethics Board of the Hospital for Sick
Children in Toronto, Canada. The Office of the Chief Coroner of
Ontario conducts research in the public interest for the purpose of
preventing future deaths and disseminates the findings of this
research to the public on a regular basis. The authority to collect
and analyze information about deaths in order to prevent future
deaths in the public interest is provided in section 15(1) of the
Ontario Coroners Act. The ability to conduct examinations and
analysis appropriate in the circumstances is provided by section
28(2) of the Ontario Coroners Act. The Research Ethics Board of the
Hospital for Sick Children granted a waiver of consent for next of
kin in this research study based on the following three necessary
conditions: 1) The objectives of the research cannot be reasonably
accomplished without using personal health information, 2) There
is a public interest in this research while protecting the privacy of
individuals and 3) There are adequate safeguards to protect the
privacy of individuals. It was also considered that given the subject
Table 1. Comparison of demographic characteristics between opioid-related mortalities and non-opioid drug related mortalities
in Ontario for the years 2006, 2007, and 2008.
Demographic Characteristics Opioid deaths (n=1359)Non-opioid deaths (n=971)p-value
Gender Male867 (63.8%) 572 (58.9%)a
AgeMedian (IQR) 44 (35–51) 46 (37–54)
Coroner Death Classification
Accident 924 (68.0%)437 (45.0%)
Undetermined 221 (16.3%)163 (16.8%)0.73
Suicide 214 (15.7%)371 (38.2%)
aTwo values not available. All tests were performed by Pearson’s Chi-square unless otherwise indicated.+Mann-Whitney U-test. Note: 20 files were not available for
assessment or contained missing information.
Table 2. Opioid-related deaths in Ontario between the years 2006 and 2008, by type of opioid.
A. Deaths in which a single opioid has been implicated (n=1040)
OpioidNumber (% of 1040)
Morphine (major)283 (27.2)
6-MAM (heroin) confirmed48 (17)
Codeine (minor)47 (17)
Codeine (only)63 (6.1)
B. Type of opioids detected across all opioid-related deaths (n=1359)*
OpioidNumber (% of 1359)
*One person could have used multiple opioids.
6-MAM: 6-monoacetyl morphine (heroin metabolite).
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group was deceased individuals, contacting the families would
cause distress. The data collected in this study was coded and
analyzed anonymously. No personal identifiers were collected.
Ontario is the most populous province in Canada with an
estimated population of 12.69 million in 2006, rising to 12.93
million in 2008. Under the Ontario Coroners Act, all sudden and
unexpected deaths, and/or deaths thought to be from any cause
other than disease must be reported to the Coroner’s Office from
anywhere in the province of Ontario. The coroners’ death
investigations involve classification of the cause of death as well
as the manner of death according to five categories: homicide,
accident, suicide, natural, and undetermined. Particularly relevant
to this study were the classification of accidental death (due to an
occurrence, incident, or event that happens without foresight or
expectation), suicide (an intentional act of omission or commission
in a person knowing the probable consequence of what he/she is
about to do), and undetermined [(a) there is no evidence for any
specific classification; (b) there is equal evidence, or a significant
contest, among two or more classifications, or (c) a death is a
suicide that does not meet a high degree of probability].
The records of the Office of the Chief Coroner of Ontario were
examined and all deaths coded as drug and alcohol-related
between 2006 and 2008 were reviewed. From these files, all deaths
in which opioids had been identified by the coroner were isolated.
Medical, toxicological, pathological, and police reports compiled
as part of the coroner’s report were comprehensively reviewed.
Narratives, semi-quantitative, and quantitative variables were
extracted, tabulated, and analyzed. Indicators of opioid misuse
and diversion were assessed amongst all opioid-related fatalities. A
nonmedical route of drug administration was determined from
coroner, police, and/or autopsy findings (i.e. death scene
investigations, puncture sites on body, patch debris). Indicators
of diversion were based solely on narratives found in coroner and
police reports. These reports were informed by coroner and police
analysis of prescription records, prescription bottles, interviews
with family and friends, consultations with healthcare providers,
and other circumstantial data gathered as part of the death
In addition, factors which have been validated for predicting
risk of opioid misuse or addiction in patients were assessed in this
cohort. In particular, data on gender, age, psychological disease,
and personal history of substance abuse as reported in the Opioid
Risk Tool (ORT)  were evaluated. Descriptive statistics (mean,
standard deviation, median, minimum, and maximum) were
calculated. Pearson’s Chi-square, Fischer Exact, Student T-test,
and Mann-Whitney U test were used as appropriate.
In Ontario, there were 2330 individuals whose cause of death
was deemed to be drug-related between 2006 and 2008. Opioids
were implicated in 58% (n=1359) of these cases. Individuals
whose cause of death was opioid-related were significantly
younger, were disproportionately male, and their manner of death
was significantly more likely to be deemed accidental (Table 1).
Conversely, when the deaths were due to drug toxicity but were
Figure 1. Manner of death per opioid type. This graph illustrates the relative proportion of accidental, suicide, or undetermined manners of
death per opioid type. The graph represents all single opioid-related deaths in Ontario, Canada between the years 2006 and 2008 (n=1040
Table 3. Indicators of diversion and opioid misuse amongst
opioid-related deaths in Ontario (n=1353).
Health worker diverting for personal use8 (0.6)
Double-doctoring (intentional)28 (2.1)
Opioid was known to be purchased from a street source 26 (2)
Using someone else’s opioid(s) n=101
Live family member/partner57 (4.2)
Deceased family member5 (0.4)
Inappropriate route n=263
Intravenous use219 (16)
Chewing fentanyl patch 14 (1.0)
Inhalation/Other 30 (2.2)
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non-opioid related, a significantly higher proportion of suicidal
overdoses were observed (Table 1). Oxycodone (35%) was
involved in approximately one-third of all opioid-related deaths,
followed by morphine (28%) and methadone (15%) (Table 2).
Oxycodone was also associated with the highest proportion of both
accidental deaths and suicides. However, when analyzing the
proportion of the types of deaths (accident, undetermined or
suicide) within each opioid type, methadone had the highest
relative percentage of deaths which were accidental (84%), while
codeine had the lowest proportion of accidental deaths (32%)
Opioid self-administration by inappropriate route of injection,
inhalation, or patch ingestion was identified in 19% of all
individuals (Table 3). Prior to death, 101 individuals (7.4%) had
used opioid medications which were diverted and had belonged to
their partners, family members or friends (Table 3). Signals of
double-doctoring, purchasing opioids from a street source, and of
health workers diverting opioids for personal use were detected in
2.1%, 2%, and 0.6% of all cases, respectively (Table 3).
Prior to death, 50 individuals (3.7%) had been switched to a
more potent opioid medication (Table 4); an additional 9
individuals had received opioids for acute pain while in methadone
programs and another 7 had their methadone dose adjusted prior
to the fatality. Further analysis was performed to identify factors
specifically associated with accidental versus suicidal overdose with
opioids. Individuals whose manner of death was accidental were
younger and were more likely to have a history of substance abuse
as compared to those committing suicide (Table 4). These
individuals were significantly more likely to be enrolled in
methadone programs and had a higher incidence of cirrhosis,
Table 4. Health characteristics amongst Ontarians whose cause of death was related to opioids; compared by manner of death.
Health and disease characteristics
(n=215) OR95% CIP-value
Cancer history 24 (2.6)17 (7.9)3.21 1.7–6.10.0002
Disability/wheelchair bound43 (4.7) 14 (6.5) 1.420.8–2.7 0.265
Lung/airway disease106 (11) 22 (10)0.880.5–1.4 0.593
Diabetes history 60 (6.5)17 (7.9) 1.230.7–2.2 0.464
Hepatitis123 (13) 3 (1.4)
Cirrhosis70 (7.6) 5 (2.3)
+ADD, OCD, bipolar, and/or schizophrenia 83 (9)36 (17) 2.11.4–3.2 0.0005
Depression 167 (18)112 (53.6) 5.2 3.8–7.1
Previous suicide attempts37 (4.0) 72 (33)12.0 7.8–18.6
Substance abuse-related features
Age (16–45)563 (61)74 (35)2.92.1–3.9
Personal history of alcohol abuse221 (24)25 (12)2.31.5–3.60.0001
Alcohol detected302 (33)64 (30)0.860.6–1.20.392
Personal history of illegal drug abuse486 (53)17 (8.1)8.35.3–12.8
Cocaine/benzoylecgonine detected308 (34)22 (11)4.342.7–6.9
Personal history of prescription drug abuse457 (50)35 (16.7)4.93.3–7.2
Last dispensed medication and/or health care visit (days)*2 (1–5)*5 (2–13)
Number of known prescribed medications*2 (0–5)*4 (2–7)
Opioid indication: Methadone program79 (8.6)4 (1.9)
Opioid indication: Chronic Pain307 (33)111 (52)2.141.6–2.9
Opioid indication: Acute pain66 (7.2)10 (4.7)0.630.3–1.250.184
Recent opioid switch (n=50) in overall cohort: Methadone 15 (1.1); Oxycodone 10 (0.7); Fentanyl 10 (0.7); Hydromorphone 4 (0.3); Morphine 3(0.2); Others 8 (0.6).
All tests were performed by Chi-square and reported as number (percent) unless otherwise indicated.
+Attention Deficit Disorder, Obsessive-Compulsive Disorder, or Bipolar, Schizophrenia with or without depression.
#Fisher Exact test.
*These values are reported as median (inter-quartile range).
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hepatitis, and cocaine use prior to death (Table 4). In 242
accidental deaths, the deceased had contact with a healthcare
worker (physician or pharmacist) less than 5 days before death
(Table 4). Individuals who committed suicide were significantly
more likely to have received a larger number of medications, to
have had previous suicide attempts, depression and/or other
psychiatric morbidities, and to have had a history of cancer and
chronic pain (Table 4).
There were 46 individuals (,3% of opioid-related deaths
between 2006 and 2008) whose death was temporally related to
custody or release from a correctional facility (Table 5). Over
90% of these deaths were accidental, 20% occurred while the
individual was in custody, and a further 43% occurred within 7
days of release from jail (Table 5). Forty percent of these
individuals were found to have injected opioids, and cocaine was
detected in 65% of these cases (Table 5).
Amongst all deaths in Ontario that were due to drug
intoxication/overdose, a far greater proportion of accidental
deaths were identified when opioids were involved. Conversely, in
non-opioid related deaths, a significantly higher proportion of
suicide was observed. This demonstrates the potential role that
opioids play in the genesis of accidental deaths, where unforgiving
margins of prescribing or ingesting errors can be lethal and
necessitate great caution on the part of prescribers and users.
Oxycodone was involved in approximately one third of opioid-
related deaths. This drug has been associated with the rising
number of opioid deaths in the province of Ontario [2,11]. In
parallel however, there have also been dramatic increases in the
use of fentanyl, hydromorphone, and methadone in Canada over
the same time frame [16–18]. When we evaluated the manner of
death based on opioid type, a high proportion of accidental deaths
occurred amongst methadone, hydromorphone, and fentanyl
users. This and other data [19–21] suggests that a range of
prescription-opioids constitute this public health crisis, particularly
as more individuals are enrolled in treatment programs for
prescription-opioid addiction [22–24], or are switched from
oxycodone to other potent opioids.
One in five individuals whose cause of death was related to
opioids utilized an inappropriate route of drug administration such
as injection, inhalation, or chewing pills or patches. Diversion
occurred in 7.4% of the deaths, including 8 cases in which
healthcare workers diverted opioids for their personal use. Opioids
were known to be purchased from the street in approximately 2%
of opioid-related deaths, however identifying the root source of
diverted opioids beyond what can be gleaned from interviews,
witnesses, and the immediate death scene investigations is limited
in coroner-led investigations. Notwithstanding, these figures assist
with quantifying the contribution of opioid abuse and illicit opioid
diversion to mortality in Ontario, and buttresses arguments that
support greater utilization of drug monitoring and other surveil-
lance systems  directed at promoting appropriate use while
discouraging abuse and diversion.
Switching to a more potent opioid, adding an opioid to someone
taking methadone, or adjusting a methadone dosage, was
associated with accidental opioid-related deaths. These are
practices which present healthcare providers with unique and
potentially lethal outcomes if not done with great caution.
Enlisting the aid of collaborative expertise such as pharmacists,
pharmacologists or addiction medicine consultants might assist
practitioners faced with these situations. Recent data suggests that
approximately 18% of individuals in the methadone program in
Ontario received at least one prescription for non-methadone
The Opioid Risk Tool (ORT) was applied posthumously for a
limited number of parameters including personal history of
substance abuse, age, and mental illness. A personal history of
substance abuse, particularly illicit or prescription drugs, and a
younger age were more likely to be associated with accidental
overdose. For suicidal deaths, depression and mental illness were
strongly correlated with deliberate overdose. In addition, a history
of previous suicide attempts was known in one-third of those who
committed suicide with opioids (versus just 4% of those whose
manner of death was accidental). Yet the ORT is specifically
designed to assess the risk for opioid abuse or addiction. While
there may be an overlap between predictors for opioid abuse or
addiction and predictors for opioid-related death, the sheer
magnitude of individuals who succumb to opioid-related toxicity
necessitates the need to identify individuals at risk specifically for
opioid overdose. Such an assessment should consider a specific
question directed at whether the potential recipient of an opioid
prescription has ever attempted suicide in the past.
Opioid-related deaths occurred while individuals were incar-
cerated and/or shortly after release. Almost all of these deaths
were accidental, and 43% occurred within one week of release. In
addition, 39% utilized injection as the preferred administration
route, and 65% had evidence of cocaine or its metabolites present.
A high rate of acute drug-related mortality amongst prison
populations in the immediate post-release period has been
described in other settings [27–29]. A contributing factor is
decreased tolerance during incarceration. Upon release, individ-
uals may utilize previous doses based on their beliefs regarding
their own tolerance. Almost 90% of post-release substance abuse
Table 5. Opioid-related deaths in Ontario which were
temporally associated with release from a correctional
institution or under custody (n=46).
Descriptor Number (%)
Male 41 (89)
Timeframe of detainment (days)
Accidental death43 (93.5)
Drugs administered by injection 18 (39)
Alcohol detected8 (17)
Cocaine and/or benzoylecgonine detected30 (65)
History of mental illness7 (15)
Main opioid detected
Methadone 11 (24)
Days released from jail
In custody9 (19.6)
1–7 days 20 (43.5)
.1–4 weeks9 (19.6)
‘‘Recent’’ (not defined)8 (17.4)
*These values are reported as median (inter-quartile range).
+Based on seven cases in which information pertaining to the length of
detainment was available.
Opioid-Related Death & Opioid-User Characteristics
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deaths in Australia, England and Wales, and Switzerland involved Download full-text
opioids . Our findings point to the need for opioid substitution
treatment interventions during incarceration and a coordinated
effort between prison and public health systems to provide
education to inmates on these issues.
Our current analysis is limited by several factors. All data in this
study were obtained from coroners’ reports, but there is variability
among coroners in how death investigations are conducted across
the province. Furthermore, toxicology testing in Ontario for
coroners’ cases is not standardized and depends on the individual
scientists in charge of the case, the history of drug use as collected
by the coroner, and the volume and type of samples available. The
drug fentanyl, for example, was not part of the regular toxicology
screen at the time of these fatalities and needed to be specifically
requested . Thus, certain drugs may be underrepresented in
our study cohort based on these differences. Finally, we did not
include an in-depth assessment of drug-interactions associated
with this study cohort. Drug interactions and an examination of
genetic mechanisms which may predispose certain individuals to
these fatalities will be the subject of a subsequent investigation by
It is evident that opioid-related mortality is associated not only
with high risk prescribing, but also with personal characteristics of
individuals who receive or use this class of drugs. Previous studies
which illustrate the short-term safety and efficacy of prescription
opioids excluded patients with substance abuse disorders ; but
in this present population-based study, there was an overrepre-
sentation of individuals with a history of drug abuse. In particular,
one in five decedents had self-administered opioids inappropri-
ately. We also identified other vulnerable Ontarians including
those involved in the correctional system, those with previous
history of suicide, those whose doctors had recently switched their
opioid medication, and those involved in a methadone program.
Our multifaceted findings point to the need for diverse prevention
strategies to be developed based on subpopulations of opioid users.
The authors would like to thank Dr. Karen Woodall and Ms. Patricia
Solbeck from the Ontario Centre of Forensic Sciences for toxicology
consultation, and Dr. David Chiasson from the Hospital for Sick Children
for pathology consultation.
Conceived and designed the experiments: PM GK. Performed the
experiments: PM. Analyzed the data: PM. Contributed reagents/
materials/analysis tools: DH AL. Wrote the paper: PM. Data interpreta-
tion: PM GK DH AL. Critically revised the manuscript for intellectual
content: AL DH GK.
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