Toblin et al
491 J Clin Psychiatry 71:4, April 2010
Mental Illness and Psychotropic Drug Use
Among Prescription Drug Overdose Deaths:
A Medical Examiner Chart Review
Robin L. Toblin, PhD; Leonard J. Paulozzi, MD;
Joseph E. Logan, PhD; Aron J. Hall, DVM; and James A. Kaplan, MD
Objective: Between 1999 and 2006, there was
a 120% increase in the rate of unintentional drug
overdose deaths in the United States. This study
identifies the prevalence of mental illness, a risk
factor for substance abuse, and chronic pain among
prescription drug overdose deaths in West Virginia
and ascertains whether psychotropic drugs contrib
uting to the deaths were used to treat mental illness
or for nonmedical purposes.
Method: In 2007, we abstracted data on mental
illness, pain, and drugs contributing to death from
all unintentional prescription drug overdose deaths
in 2006 recorded by the West Virginia Office of the
Chief Medical Examiner. Decedent prescription
records were obtained from the state prescription
drug monitoring program.
Results: Histories of mental illness and
pain were documented in 42.7% and 56.6% of
295 decedents, respectively. Psychotropic drugs
contributed to 48.8% of the deaths, with benzo
diazepines involved in 36.6%. Benzodiazepines
contributing to death were not associated with
mental illness (adjusted odds ratio [AOR] = 1.1;
95% CI, 0.6–1.8), while all other psychotropic
drugs were (AOR = 3.9; 95% CI, 2.0–7.6). Of
decedents with contributory benzodiazepines,
46.3% had no prescription for the drug.
Conclusions: Mental illness may have con
tributed to substance abuse associated with deaths.
Clinicians should screen for mental illness when
prescribing opioids and recommend psychotherapy
as an adjunct or an alternate to pharmacotherapy.
Benzodiazepines may have been used nonmedi
cally rather than as a psychotropic drug, reflecting
drug diversion. Restricting benzodiazepine pre
scriptions to a 30day supply with no refills might
J Clin Psychiatry 2010;71(4):491–496
© Copyright 2010 Physicians Postgraduate Press, Inc.
Submitted: July 28, 2009; accepted October 5, 2009
Corresponding author: Robin L. Toblin, PhD, Office of Research and
Evaluation, Federal Bureau of Prisons, 320 First St NW, Washington, DC
States, increasing by 120% during the years 1999–2006.1
This increase has largely been attributed to prescription
drugs, rather than to illicit drugs. Most of the problem is
due to deaths from opioid analgesics2; these deaths have
increased in parallel with the number of prescriptions for
such drugs.3 While studies have focused on the role of
chronic pain, drug diversion, and “doctor shopping” in pre
scription drug overdose deaths,4,5 few studies of these deaths
have focused on mental health problems and the medica
tions used to treat such problems.
Previous research has found that those who have mental
disorders are more likely to have drug use disorders (ie, drug
abuse and drug dependence).6 Approximately 15%–20% of
persons with mental disorders have a drug use disorder at
some point in their lifetimes.6,7 People who report having a
diagnosis of major depressive disorder within the past year
are 3.7 times more likely to report drug dependence.6 In
addition, people with mental disorders are twice as likely as
those without mental disorders to use prescribed opioids.8
Other epidemiologic studies have examined the mental
disorders of those persons with drug use disorders. One
study found that over half (53%) of persons with drug
use disorders had non–substance abuse mental disorders,
or 4.5 times the odds of persons without drug disorders.7
Another epidemiologic survey found that 32% of drug abus
ers had mood disorders, while 25% had anxiety disorders9;
the study also found that nonmedical use of opioids was
strongly associated with mood disorders, anxiety disorders,
and personality disorders.10 Further, research regarding
prescription drug overdose deaths suggests that a large pro
portion of decedents had histories of mental illness.4
In general, studies of deaths from drug overdoses have
supported such selfreported associations.11 In New Jersey,
for example, 24.4% of persons who died of unintentional
drug overdoses had histories of mental health risk factors.5
However, the prevalence of mental illness may be higher
for deaths involving prescription drugs, some of which are
prescribed for mental disorders. Studies of deaths involv
ing both illicit drugs and prescription opioids have reported
a high likelihood of finding prescription psychotropic
drugs (ie, drugs prescribed to treat mental disorders) on
eaths resulting from unintentional drug overdoses
have risen to epidemic proportions in the United
Mental Illness and Prescription Drug Overdose Deaths
J Clin Psychiatry 71:4, April 2010 492
postmortem toxicology reports,12 even though such drugs
are rarely responsible for overdose deaths by themselves.4
One aspect of the association between mental illness and
psychotropic drugs that has not been examined is whether
psychotropic drugs involved in prescription drug overdoses
have been prescribed to treat mental illness or are being
used nonmedically as part of a substance use disorder.
Benzodiazepine sedatives, for example, are prescribed for
anxiety disorders, but they are also often combined with
drugs that produce a euphoric effect, such as heroin or pre
scription analgesics, and are addictive in their own right
when misused.13 Therefore, one aim of this study was to
determine the prevalence of mental illness and psychotropic
drug involvement in a population that had died of prescrip
tion drug–related overdoses and the overlap between the
In addition, little is known about how persons with
mental illness and a history of chronic pain come to use
prescription painkillers. Therefore, a second aim of the pre
sent study was to describe the association between mental
illness and chronic pain among drug overdose deaths. Our
hope was to identify associations among mental illness, psy
chotropic drugs, and pain to help guide prevention efforts
in reducing prescription drug overdose deaths.
Case Identification and Data Sources
All decedents were West Virginia residents who died
within the state in 2006. West Virginia was selected because
it experienced the largest increase (675%) in the uninten
tional drug overdose mortality rate among all US states
between 1999 and 2004.1 Decedent records were reviewed if
the death certificates listed the underlying cause of death as
unintentional drug poisoning (International Classification of
Diseases, 10th Revision [ICD-10] codes X40–X44). All cases
were identified via an electronic database of vital records at
the Health Statistics Center of the West Virginia Depart
ment of Health and Human Resources using the appropriate
ICD-10 codes. Identifying information was crossreferenced
with the case logbook and electronic database of the in
vestigations of the Office of the Chief Medical Examiner
(OCME) to identify decedent records. We excluded all de
cedents certified without benefit of autopsy as well as those
decedents in whom the only drugs contributing to death
were illicit or overthecounter drugs. In West Virginia, the
chief toxicologist routinely screens all potential victims of
drug overdose for illicit and prescription drugs. Trained
and certified death investigators conduct sceneofdeath
investigations and write reports on all drugrelated cases.
Subsequently, OCME staff forensic pathologists review
these reports, medical records, decedents’ prescription re
cords, autopsy and toxicology findings, and other evidence
to determine which factors, including drugs, are contribu
tory to death.
In late 2007, we abstracted information from autopsy
reports, toxicology reports, deathscene investigation re
ports, death certificates, and copies of medical records in the
OCME files. The West Virginia Board of Pharmacy also pro
vided decedent prescription histories available through the
state’s Controlled Substances Monitoring Program (CSMP),
which, since its inception in 2003, has maintained electronic
records of all Schedule II, III, and IV, and prescribed Sched
ule V controlled substances* dispensed by all pharmacies
licensed by the State of West Virginia.
We characterized the decedents in terms of sociodemo
graphic factors, history of chronic pain, and history of
mental illness. Demographic information on the decedents,
including sex, age, marital status, and highest level of edu
cation, was collected from death certificates. The OCME
death scene investigation reports, medical records, and
autopsy reports were also used to determine past medical
histories and comorbidities.
A history of mental illness (hereafter referred to as men
tal illness) was derived from diagnoses recorded in medical
records and information reported to death scene investiga
tors. Specific diagnoses could not be independently verified
with criteria from the Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition (DSM-IV) due to the study
population of decedents. Thus, diagnoses were recorded
as they appeared, even when mutually exclusive disorders
were listed. Disorders were grouped into major diagnostic
categories. However, 2 individual disorders, major depres
sive disorder and bipolar disorder, were recorded separately
because they are strongly associated with substance abuse
and chronic pain and have different pharmacotherapies.
A history of pain was identified from medical records
and death scene investigation records. Pain was classified
by anatomic system as decided before our investigation.
The nature and location of the pain was used to classify
the pain as subjective—the source of the pain was likely to
be taken from the patient’s own statement; objective—the
pain was likely to be apparent from physical findings; and
unclassifiable. Subjective pain included that of fibromyalgia,
headaches, neck/back, and neuralgia. Objective pain includ
ed that of cancer, infection, recent dental work, and trauma.
Unclassifiable pain included arthritis, gastrointestinal, geni
tourinary, heart/chest, and orofacial pain.
We also assessed the proportion of cases that had at least
1 psychotropic drug contributing to death, as determined
by the OCME. Psychotropic drugs were prescription drugs
usually used to treat mental disorders. We categorized
*As defined by the Controlled Substances Act, the term controlled substance
means a drug or other substance, or immediate precursor, included in
Schedule I, II, III, IV, or V, available at http://www.usdoj.gov/dea/pubs/csa.
html. Narcotic painkillers are primarily Schedule II, and benzodiazepines
are Schedule IV.
Toblin et al
493 J Clin Psychiatry 71:4, April 2010
psychotropic drugs into drug class on the basis of the drug
reference vocabulary established by the Drug Alert and
Warning Network.12 Drug classes included benzodiaz
epines, antidepressants, and “other psychotropics,” which
included anticonvulsants and antipsychotics, among others.
We used information from both the CSMP and the OCME
to determine whether decedents using benzodiazepines had
prescriptions for those drugs.
First, we calculated the prevalence of mental illness and
specific disorders as well as classes of contributory psycho
tropic drugs. We then used multiple logistic regression to
examine the association between mental illness and psy
chotropic drugs, controlling for age and sex, which were
found to be significantly associated with mental illness in
univariate models. We ran multiple logistic regressions to
determine if each drug class was associated with mental
Next, we compared decedents with and without mental
illness, using multiple logistic regression to examine asso
ciations with demographic factors. Except for cases in which
age was the variable of interest, age was used as a continuous
variable. Consistent with census methodology,14 we limited
the analysis of highest level of education attained to dece
dents aged ≥ 25 years. For analyses that involved cell sizes
less than 5, the Fisher exact test was used.
We also calculated the associations between demo
graphic variables and having at least 1 psychotropic drug
contributory to death, having a benzodiazepine as the only
psychotropic drug, and having at least 1 psychotropic drug
that was not a benzodiazepine. We examined benzodiaz
epines independently due to their propensity for abuse.
We used available information on prescription history
to further characterize how benzodiazepines were being
used. We conducted a CochraneArmitage test for trend in
the association between mental illness and the number of
benzodiazepines prescribed. We also identified the propor
tion of decedents who had been prescribed benzodiazepines
that contributed to death.
Finally, controlling for sex and age, we conducted a series
of multiple logistic regressions to look at the association
between mental illness and varied types of pain by com
paring decedents with each pain type to decedents with
no pain: a history of any pain; subjective, unclassifiable, or
objective pain; and specific subtypes of pain. All analyses
were conducted by use of SAS software, Version 9.1 (SAS
Institute Inc, Cary, North Carolina).
The study included 295 decedents who met inclusion
criteria. Men composed 67.1% of the study population.
More than half of the decedents (53.2%) were 35–54 years
of age, while 38.6% were aged 18–34 and the remainder
(8.1%) were aged 55 or older. Roughly half of the dece
dents (51.6%) had a high school education, a third (31.0%)
had not graduated from high school, and the remainder
(17.3%) had some college. Marital status was about evenly
split between never married (34.9%), married (32.9%), and
divorced or widowed (32.2%).
Of these 295 decedents, 126 (42.7%) had a history of
mental illness other than substance abuse (Table 1). Mood
disorders and anxiety disorders were most prevalent. A
history of pain was found in 56.6% of decedents. Opioid
analgesics contributed to 93% of the deaths. Psychotropic
drugs contributed to 48.8% of all deaths (Table 1).
Table 1. Prevalence of Key Variables Among Persons Dying
of Prescription Drug Overdoses in West Virginia in 2006
(N = 295)
Mental illness (excludes substance abuse)a
Major depressive disorder
All other disorders
Substance abuse disordersb
Alcohol use disorder
Any psychotropic drug
Antidepressant or other psychotropic drugc
Other psychotropic drug
aMental illness classification is based on a history of mental illness as
found in medical records or reported in death investigations; categories
are not mutually exclusive, so that totals exceed 100%.
bAlthough substance abuse disorders are considered mental disorders,
in this study, mental illness refers to non–substance abuse mental
cOther psychotropic drugs include carbamazepine, hydroxyzine,
phenobarbital, quetiapine, topiramate, and zolpidem.
Table 2. Association of History of Mental Illness and
Contributory Drug Classes in West Virginia in 2006
Contributory Drug Class
Any psychotropic drug
Antidepressant or other
Other psychotropic druge
aNumber and percent of decedents with a history of mental illness
among all deaths involving this class of drugs.
bReferent is all others not included in each row.
cBoldface type indicates statistical significance.
dDecedents with these contributory drugs may also have had a
eOther psychotropic drugs include carbamazepine, hydroxyzine,
phenobarbital, quetiapine, topiramate, and zolpidem.
Mental Illness and Prescription Drug Overdose Deaths
J Clin Psychiatry 71:4, April 2010494
variables examined (Table 3). There was no association
between demographics and benzodiazepines as the only
contributory psychotropic drug or between demographics
and having at least 1 contributory antidepressant or “other”
psychotropic (not shown).
Of decedents with contributory benzodiazepines, 53.7%
had prescriptions for all benzodiazepines; the remaining
46.3% had at least 1 benzodiazepine for which they did not
have a valid prescription. Regardless of whether benzodiaz
epines were involved in the decedent’s fatal overdose, the
number of different benzodiazepines prescribed in the year
prior to death (eg, diazepam versus alprazolam) was sig
nificantly associated with mental illness in a doseresponse
fashion (test for trend: Z = −5.3, P < .001). The odds ratios
were 2.5, 3.5, and 5.2 for 1, 2, and 3 or more unique benzodi
azepines prescribed in the year prior to death, respectively.
Most decedents (56.6%) had a history of pain. Decedents
with both subjective and unclassifiable pain were more
likely to have mental illness (Table 4). The association with
mental illness varied by pain subtype. Neck and back pain,
headaches, and arthritis were all associated with mental ill
ness, with odds ratios of 4.6, 4.5, and 3.6, respectively.
We found that nearly onehalf of the people dying from
a prescription drug overdose in West Virginia in 2006 had a
history of mental illness during their lifetime and that over
onehalf had a history of chronic pain. Psychotropic drugs
contributed to nearly onehalf of the overdoses in this study
population, usually in combination with an opioid; of these,
about threefourths of those deaths involved a benzodiaz
epine. We found that psychotropic drugs were associated
with mental illness, but, for benzodiazepines, specifically,
there was no association with mental illness. Mental illness
Table 4. Association of Pain Subtypes and Mental Illness as
Compared to Decedents With No Pain in West Virginia in 2006
with no pain)
aNumber and percent of decedents in each row who had a history of
bAdjusted for age and sex.
cBoldface type indicates statistical significance.
dIndicates an association with cell sizes too small to conduct multiple
Table 3. Characteristics of Decedents With History of Mental Illness and Decedents With Contributory Psychotropic Drug Use in
West Virginia in 2006 (N = 295)
Mental Illness (n = 126)
Deaths, nMental Illness
Age group, y
≥ 5524 58.3
Never married10327.80.6 (0.3–1.2)
Less than high school7744.1Reference
High school diploma12843.81.1 (0.6–2.0)
Some college4358.11.8 (0.8–4.0)
aAdjusted for age and sex.
bBoldface type indicates statistical significance.
cEducation calculated only for those aged ≥ 25 years (n = 248).
Any Psychotropic Drug (n = 144)
Psychotropic Drug at DeathCharacteristic
Percent With Adjusted Odds Ratioa,b
Adjusted Odds Ratioa
Decedents with mental illness had over twice the odds
of having a psychotropic drug contribute to death and were
nearly 4 times as likely to have had an antidepressant or
“other” psychotropic drug contribute to death, compared
to decedents without mental illness. However, benzo
diazepines contributing to death were not associated with
mental illness (Table 2).
Mental illness was associated with female sex and greater
age, while no associations were identified between con
tributory psychotropic drugs and any of the demographic
Toblin et al
495 J Clin Psychiatry 71:4, April 2010
was associated with sex, age, and both subjective and unclas
sifiable pain; therefore, we were surprised that psychotropic
drugs, commonly used to treat mental health problems, were
not associated with these same demographic or pain vari
ables. These findings suggest that benzodiazepines are being
diverted and used nonmedically.
Although mental illness was common in our study, its
prevalence is comparable to the lifetime prevalence in the
United States as a whole.15 The prevalence of mood dis
orders, including major depressive disorder and bipolar
disorder, was higher than national figures. Anxiety disorders
and sleep disorders were lower in study decedents than in
national data, and psychotic disorders were equivalent. The
increased rate of mood disorders in this study is not surpris
ing in light of the fact that substance use disorders and mood
disorders are highly correlated.15
There was a significant association between contributory
psychotropic drug use and mental illness. This association
was strong for antidepressant and other psychotropic drug
classes, but it did not hold for benzodiazepines, which consti
tuted the largest proportion of psychotropic drugs. However,
the significant doseresponse relationship between the num
ber of prescriptions for different benzodiazepines and mental
illness suggests that some benzodiazepines were being used
medically. Perhaps those with multiple prescriptions had
a specific mental illness requiring more complex treat
ment, whereas those with complaints of nonspecific anxiety
received a prescription without a diagnosable illness. None
theless, the widespread use of benzodiazepines by people
without mental illness and the finding that 46.3% of people
did not have prescriptions for at least 1 benzodiazepine that
contributed to death suggest that abuse of benzodiazepines
was involved. This finding is consistent with the known use
of benzodiazepines by drug abusers to moderate the effects
of cocaine, heroin, or opioids and the Drug Enforcement
Administration’s opinion that benzodiazepines are among
the most commonly abused drugs in West Virginia.16
While we found that female decedents in this study were
nearly twice as likely as male decedents to have mood and
anxiety disorders, consistent with national findings in the
general population,15 we found no association between sex
and psychotropic drug involvement in the overdoses, a find
ing not consistent with data demonstrating that women are
more likely to be prescribed psychotropic drugs than men
in the United States.17–19 Because men composed twothirds
of the study population, this lack of association is very likely
due to the high prevalence of nonmedical use and diver
sion of psychotropic drugs in this population and the known
association between male sex and drug abuse.4,20 Although
the literature does not suggest that increasing age is a risk
factor for mental illness, we found that, in our population,
increasing age was associated with mental illness but not
with psychotropic drug involvement. However, there may
be differences between a decedent population and the gen
The association we found between mental illness and
pain is consistent with the literature. The World Health
Organization suggests that people with chronic pain have
a 4fold increase in anxiety and depressive disorders.21
Among decedents dying of drug overdoses, however, we
found that mental illness was associated with only certain
types of pain. There are several potential explanations for
this finding. People without a physically verifiable cause
of pain may have been more likely to have been labeled as
mentally ill. Alternatively, people with mental illness may
have been more likely to seek care and complain of some
types of pain. Underlying symptoms of mental illness tend
to exacerbate the intensity of and focus upon one’s pain.22
Finally, given the established association between substance
abuse disorders and other mental illnesses, individuals with
such disorders might use subjective pain complaints as a
mechanism to obtain prescription drugs for nonmedical
purposes. The comorbidity of substance abuse and other
mental disorders generates such complaints when patients
realize they have a high likelihood of obtaining narcotic
The limitations of this study are the result of substantial
uncertainties inherent in the nature of death investigation
systems and CSMP prescription data collection. First, the
diagnosis of mental disorders and reporting of pain were
based upon the OCME records, which were not always
consistent among data sources. For instance, medical re
cords were available for only 43% of decedents, and not all
deathscene investigation reports addressed mental illness.
Further, some diagnoses were based on reports by friends
and family and, therefore, may not have met true criteria for
diagnosis. In addition, listing of deathscene medications
and statewide CSMP data collection were incomplete, and
CSMP data were limited to scheduled drugs; thus, no reli
able analyses of the prescription history for antidepressants
and other psychotropic drugs could be conducted.
Clinicians should assess pain patients for a history of
both drug abuse and mental illness. Currently, clinicians
are told to use caution in their prescribing of opioids to
people with a history of substance abuse.23 This guidance
should also apply for prescribing to patients with a history
of mental illness, particularly if patient reports of pain have
no physical findings. Chronic pain has high comorbidity
with anxiety and mood disorders. Clinicians should con
sider referring patients for psychotherapy because it has
been shown to be an important adjunct in the treatment of
chronic pain24 and may reduce the need for opioid analge
sics. Further, cognitivebehavioral therapy has been shown
to be highly effective in treating adult anxiety disorders,25
and such therapy may reduce the need for benzodiazepines.
Clinicians should be cautious when prescribing opioids
Mental Illness and Prescription Drug Overdose Deaths Download full-text
J Clin Psychiatry 71:4, April 2010496
and benzodiazepines concurrently for chronic pain, even
in patients without mental illness, unless there is a specific
medical indication.23 Judicious prescribing of opioid analge
sics and benzodiazepines not only might help prevent abuse
in patients but also might reduce the ambient level of drugs
subject to abuse in the community.
States can also employ administrative tools to address the
problem of abuse of psychotropic drugs. West Virginia and
other states with benzodiazepine abuse problems should
consider treating benzodiazepines, currently Schedule IV
drugs, like Schedule II drugs by specifically restricting them
to a 30day supply with no refills. States with prescription
drug abuse problems should also consider expanding their
use of prescription drug monitoring program data for case
management and surveillance. With these data, clinicians
and pharmacists could monitor their patients’ prescrip
tions, medical examiners could review the drug use history
of decedents, and public health agencies could better iden
tify provider characteristics and highrisk populations for
prescription drug abuse as well as the impact of prevention
Drug names: alprazolam (Xanax, Niravam, and others), carbamazepine
(Carbatrol, Equetro, and others), diazepam (Diastat, Valium, and
others), hydroxyzine (Vistaril and others) quetiapine (Seroquel),
topiramate (Topamax), zolpidem (Ambien, Edluar, and others).
Author affiliations: Epidemic Intelligence Service, Office of Workforce
and Career Development (Drs Toblin, Logan, and Hall), and National
Center for Injury Prevention and Control (Drs Toblin, Paulozzi, and
Logan), Centers for Disease Control and Prevention, Atlanta,
Georgia; and West Virginia Department of Health and Human
Resources, Charleston (Drs Hall and Kaplan).
Potential conflicts of interest: None reported.
Funding/support: None reported.
Disclaimer: The contents of this article are solely the responsibility of
the authors and do not necessarily represent the official views of the
Centers for Disease Control and Prevention.
Previous presentation: Data from this article were presented at the 58th
Annual Epidemic Intelligence Service Conference; April 20–24, 2009;
Acknowledgment: We thank Edna Wong McKinstry, MD, Epidemiology
Elective Program, Centers for Disease Control and Prevention, for her
assistance with data collection; James C. Kraner, PhD, West Virginia
Department of Health and Human Resources, for access to the toxicolo
gy data; and Danae Bixler, MD, West Virginia Department of Health and
Human Resources, and Alex E. Crosby, MD, National Center for Injury
Prevention and Control, Centers for Disease Control and Prevention, for
their contributions to the conceptualization and oversight of the overall
investigation and data collection. Drs McKinstry, Kraner, Bixler, and
Crosby report no potential conflicts of interest relevant to this article.
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