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Cited by 330Opioid Use Disorder TreatmentPoisoning and overdose treatmentsSubstance Abuse Treatment and Outcomes

National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009.

Open access
Calcaterra, Susan, Glanz, Jason, Binswanger, Ingrid A.·2013·Drug and Alcohol Dependence
DOI 10.1016/j.drugalcdep.2012.11.018PMC PMC3935414
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Abstract

Background Pharmaceutical opioid related deaths have increased. This study aimed to place pharmaceutical opioid overdose deaths within the context of heroin, cocaine, psychostimulants, and pharmaceutical sedative hypnotics examine demographic trends, and describe common combinations of substances involved in opioid related deaths.Methods We reviewed deaths among 15-64 year olds in the US from 1999-2009 using death certificate data available through the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) Database. We identified International Classification of Disease-10 codes describing accidental overdose deaths, including poisonings related to stimulants, pharmaceutical drugs, and heroin. We used crude and age adjusted death rates (deaths/100,000 person years [p-y] and 95% confidence interval [CI] and multivariable Poisson regression models, yielding incident rate ratios; IRRs), for analysis.Results The age adjusted death rate related to pharmaceutical opioids increased almost 4-fold from 1999 to 2009 (1.54/100,000 p-y [95% CI 1.49-1.60] to 6.05/100,000 p-y [95% CI 5.95-6.16; p<0.001). From 1999 to 2009, pharmaceutical opioids were responsible for the highest relative increase in overdose death rates (IRR 4.22, 95% CI 3.03-5.87) followed by sedative hypnotics (IRR 3.53, 95% CI 2.11-5.90). Heroin related overdose death rates increased from 2007 to 2009 (1.05/100,000 persons [95% CI 1.00-1.09] to 1.43/100,000 persons [95% CI 1.38-1.48; p<0.001). From 2005-2009 the combination of pharmaceutical opioids and benzodiazepines was the most common cause of polysubstance overdose deaths (1.27/100,000 p-y (95% CI 1.25-1.30).Conclusion Strategies, such as wider implementation of naloxone, expanded access to treatment, and development of new interventions are needed to curb the pharmaceutical opioid overdose epidemic.

Integrity signals

Registry

Crossref · 10.1016/j.drugalcdep.2012.11.018

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 40 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Compared with females, males were almost four times more likely to die a heroin related death (IRR 3.92, 95% CI 2.96-5.20).

    “When compared to females, males were almost 4 times more likely to die a heroin related death (IRR 3.92, 95% CI 2.96-5.20).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Non Hispanic Whites (IRR 12.20) and American Indians/Alaska Natives (IRR 13.06) had the highest rates of pharmaceutical opioid related deaths.

    “NHWs (IRR 12.20, 95% CI 8.68-17.15) and AI/ANs (IRR 13.06, 95% CI 9.30-18.34) had the highest rates of pharmaceutical opioid related deaths.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Compared with females, males had 2 to 4 times higher cocaine and psychostimulant related death rates.

    “cocaine and psychostimulant related deaths were 2 to 4 times more likely among males (Table 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Heroin-related overdose death rates increased from 2007 to 2009 (from 1.05 to 1.43 per 100,000 persons, p<0.001).

    “Heroin related overdose death rates increased from 2007 to 2009 (1.05/100,000 persons [95% CI 1.00-1.09] to 1.43/100,000 persons [95% CI 1.38-1.48; p<0.001).”
    Quote in the paperNot a substantial claim
  • Findingown data

    For pharmaceutical opioid related deaths, the male-to-female death rate ratio decreased with advancing age, from 3.6 at ages 15-24 to 1.3 at ages 55-64.

    “Males aged 15-24 years old were 3.6 times more likely to die from a pharmaceutical opioid related death than similarly aged females. The death rate ratio decreased with each advancing age group. Males aged 55-64 were only 1.3 times more likely to die from a pharmaceutical opioid related death than females of the same age group.”
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    Findingnone given

    Among pharmaceutical opioid related deaths, morphine and its derivatives accounted for the highest number of deaths across all years.

    “Among pharmaceutical opioid related deaths, morphine and its derivatives accounted for the highest number of deaths across all years (Figure 1).”
    Quote in the paperNot a substantial claim

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    Findingown data

    Psychostimulant related deaths peaked in 2005 (IRR 2.59), declined during 2006 and 2007, but were elevated again in 2009 (IRR 2.52).

    “Psychostimulant related deaths peaked in 2005 (IRR 2.59, 95% CI 1.14-5.85), declined during 2006 and 2007, but were elevated again in 2009 (IRR 2.52, 95% CI 1.11-5.71).”
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    Findingown data

    The death rate for those aged 45-55 years was highest for cocaine (IRR 6.41), followed by heroin (IRR 3.56), and pharmaceutical opioids (IRR 3.15).

    “The death rate for those aged 45-55 years was highest for cocaine (IRR 6.41, 95% CI 4.79-8.58), followed by heroin (IRR 3.56, 95% CI 2.35-5.40), and pharmaceutical opioids IRR 3.15, 95% CI 2.54-3.89).”
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    Findingown data

    The crude pharmaceutical opioid related death rate among 15-24 year olds was 0.51 per 100,000 in 1999 and peaked at 3.38 per 100,000 in 2009, a sixfold increase.

    “The crude death rate related to pharmaceutical opioids among 15-24 year olds was 0.51/100,000 persons, 95% CI 0.44-0.58 in 1999 and peaked to 3.38/100,000 persons, 95% CI 3.21-3.56 in 2009, a 6-fold increase.”
    Quote in the paperNot a substantial claim

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    Findingown data

    Heroin related deaths were elevated among Non Hispanic Whites (IRR 7.27), African Americans (IRR 7.65), and American Indians/Alaska Natives (IRR 7.00).

    “Heroin related deaths were elevated among NHWs (IRR 7.27, 95% CI 3.77-14.02), African Americans (IRR 7.65, 95% CI 3.97-14.75), and AI/ANs (IRR 7.00, 95% CI 3.62-13.56).”
    Quote in the paperNot a substantial claim

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    Findingown data

    In adjusted analyses, pharmaceutical opioids had the largest relative increase in overdose death rate from 1999 to 2009 (IRR 4.22, 95% CI 3.03-5.87), followed by sedative hypnotics (IRR 3.53, 95% CI 2.11-5.90).

    “From 1999 to 2009, pharmaceutical opioids were responsible for the highest relative increase in overdose death rates (IRR 4.22, 95% CI 3.03-5.87) followed by sedative hypnotics (IRR 3.53, 95% CI 2.11-5.90).”
    Quote in the paperSubstantial claim

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    Findingown data

    Men had higher death rates than women for combinations of pharmaceutical opioids with cocaine (1.08 per 100,000 person-years), alcohol (0.96), and benzodiazepines (1.63).

    “Men were more likely to die from a death related to the combination of pharmaceutical opioids and cocaine (1.08/100,000 p-y, 95% CI 1.05-1.11), alcohol (0.96/100,000 p-y, 95%CI 0.93-0.99), and benzodiazepines (1.63/100,000 p-y, 95% CI 1.60-1.67).”
    Quote in the paperNot a substantial claim

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    Findingown data

    Methadone related deaths rose steadily from 1999 to 2007, then decreased significantly in 2009.

    “Methadone related deaths rose steadily from 1999 (0.33/100,000 p-y, 95% CI 0.30-0.35) to 2007 (2.34/100,000 p-y, 95% CI 2.27-2.40; p<0.001), but then decreased significantly in 2009 (2.01/100,000 p-y, 95% CI 1.95-2.08; p<0.001).”
    Quote in the paperNot a substantial claim

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    Findingown data

    During 2005 to 2009, death rates varied by gender for all substances examined, with males having higher rates for each substance.

    “Death rates varied by gender for all substances during 2005 to 2009. Males had higher death rates for each substance examined.”
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    Findingown data

    The combination of pharmaceutical opioids and benzodiazepines had the highest death rate among substance combinations (1.27 per 100,000 person-years, 95% CI 1.25-1.30), followed by pharmaceutical opioids with cocaine, alcohol, and antidepressants.

    “From 2005-2009 the combination of pharmaceutical opioids and benzodiazepines was the most common cause of polysubstance overdose deaths (1.27/100,000 p-y (95% CI 1.25-1.30).”
    Quote in the paperNot a substantial claim

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    Findingreasoning

    American Indians/Alaska Natives were at high risk of dying from a psychostimulant related or a pharmaceutical opioid related death.

    “AI/ANs were at high risk of dying from a psychostimulant related or a pharmaceutical opioid related death.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The loss of significance for the 2007-2009 heroin death increase after adjustment may be related to misclassification of heroin related deaths.

    “This finding may be related to misclassification of heroin related deaths, as discussed below.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Non medical use of pharmaceutical opioids leading to injection heroin use and concomitant use of heroin and pharmaceutical opioids have been reported.

    “Non medical use of pharmaceutical opioids leading to injection heroin use and concomitant use of heroin and pharmaceuticals opioids have been reported (Siegal et al., 1994; Lankenau et al., 2012; Nielsen et al., 2011; Wilkins et al., 2011).”
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    • cites Lankenau et al., 2012 source

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    • cites Nielsen et al., 2011 source

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    Premisecitation

    Successful strategies to reduce opioid overdoses include wider implementation of rescue medications such as naloxone to reverse opioid overdose and enhanced access to drug treatment with medications such as buprenorphine.

    “Successful strategies to reduce opioid overdoses include wider implementation of rescue medications such as naloxone to reverse opioid overdose and enhanced access to drug treatment with medications such as buprenorphine (Albert et al., 2011; Centers for Disease Control and Prevention, 2012; Cornish et al., 2010).”
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    • cites Centers for Disease Control and Prevention, 2012

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    Interpretationcitation

    Tolerance to pain medications, worsening withdrawal symptoms, and increased availability and affordability of heroin relative to the high street cost of pharmaceutical opioids may push pharmaceutical opioid users to heroin.

    “Tolerance to pain medications, worsening withdrawal symptoms, and increased availability and affordability of heroin relative to the high street cost of pharmaceutical opioids may push pharmaceutical opioid users to heroin (Inciardi et al., 2009).”
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    • cites Inciardi et al., 2009 source

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    Premisecitation

    The average milligrams of morphine prescribed per patient per year increased more than 600% from 1997 to 2007, which led to an increased availability of pharmaceutical opioids for illicit use.

    “The average milligrams of morphine prescribed per patient per year increased more than 600% from 1997 to 2007, which led to an increased availability of pharmaceutical opioids for illicit use (US Department of Justice, 2012).”
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    • cites US Department of Justice, 2012

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    Study design and conductreasoning

    This may have led to an overestimation of pharmaceutical opioid related deaths and an underestimation of heroin related deaths, leading to misclassification bias in our study.

    “This may have led to an overestimation of pharmaceutical opioid related deaths and an underestimation of heroin related deaths, leading to misclassification bias in our study.”
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    Study design and conductnone given

    Toxicology findings and cause of death determinations may not be consistent between counties or states due to differing medical examiner/coroner policies.

    “Toxicology findings and cause of death determinations may not be consistent between counties or states due to differing medical examiner/coroner policies.”
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    Premisecitation

    National survey data showed that 75% of pharmaceutical opioid users were using opioids prescribed to someone else.

    “National survey data showed that 75% of pharmaceutical opioid users were using opioids prescribed to someone else (Substance Abuse and Mental Health Services Administration, 2010).”
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    • cites Substance Abuse and Mental Health Services Administration, 2010

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    Study design and conductnone given

    This study was not designed to describe additional causes of death related to substance use, such as homicides, motor vehicle crashes, and long-term sequelae of substance use.

    “This study was not designed to describe additional causes of death related to substance use, such as homicides, motor vehicle crashes, and long-term sequelae of substance use (e.g. congestive heart failure, infectious disease).”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Barriers to receiving substance abuse treatment among American Indians/Alaska Natives living in urban areas or on reservations include low insurance coverage, limited access to transportation, and discomfort in the Westernized healthcare system.

    “Barriers to receiving substance abuse treatment among AI/ANs living in urban areas or on reservations include low insurance coverage, limited access to transportation, and “discomfort” in the Westernized healthcare system (Gone and Trimble, 2012, Katz, 2004; Moulton et al., 2007; Call et al., 2006).”
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  • Classified as probably not a substantial claim.

    Study design and conductown data

    We could not ascertain the indication for pharmaceutical opioid use.

    “We could not ascertain the indication for pharmaceutical opioid use.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The prevalence of sedative hypnotic use is higher among the elderly, and risk of inappropriate use is more likely.

    “The prevalence of sedative hypnotic use is higher among the elderly, and risk of inappropriate use is more likely (Straand and Rokstad, 1999).”
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    • cites Straand and Rokstad, 1999

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    Premisecitation

    Factors which may lead to increased substance use, such as mental disorders and stress, are more prevalent among American Indians/Alaska Natives as compared to the general population.

    “Factors which may lead to increased substance use, such as mental disorders and stress, are more prevalent among AI/ANs as compared to the general population (Grant et al., 2004).”
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    Study design and conductown data

    We could not examine other risk factors for death, such as socioeconomic status or lifetime history of substance abuse.

    “We could not examine other risk factors for death, such as socioeconomic status or lifetime history of substance abuse.”
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    Premisecitation

    6-MAM can be tested for in the blood and urine, but the absence of 6-MAM does not have a high predictive value due to its short half life.

    “6-MAM can be tested for in the blood and urine, but the absence of 6-MAM does not have a high predictive value due to its short half life (Verstraete, 2004).”
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    Interpretationnone given

    Increased access and use of state run prescription drug monitoring programs may allow prescribers to identify patients who have filled multiple prescriptions for pharmaceutical medications and are at increased risk of abuse.

    “Increased access and use of state run prescription drug monitoring programs may allow prescribers to identify patients who have filled multiple prescriptions for pharmaceutical medications and are at increased risk of abuse.”
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    Study design and conductnone given

    Autopsy information was recorded beginning in 2003 on all overdose deaths and were performed 69-87% of the time.

    “Autopsy information was recorded beginning in 2003 on all overdose deaths and were performed 69-87% of the time.”
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    Premisecitation

    Over the last decade, the number of methadone prescriptions written for treatment of chronic pain and the overall sales of methadone increased.

    “Over the last decade, the number of methadone prescriptions written for treatment of chronic pain and the overall sales of methadone increased (US Government Accountability Organization, 2009; US Department of Justice, 2011).”
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    • cites US Government Accountability Organization, 2009

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    Premisecitation

    Culturally targeted substance abuse interventions may impact initiation of substance use and help in the treatment of abuse.

    “Culturally targeted substance abuse interventions may impact initiation of substance use and help in the treatment of abuse (Hetch et al., 2003; Unger, 2012).”
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    Premisecitation

    Certain sub-populations have been found to be at greater risk of inappropriate sedative hypnotic use including those with opioid and/or alcohol abuse/dependence.

    “Certain sub-populations have been found to be at greater risk of inappropriate sedative hypnotic use including those with opioid and/or alcohol abuse/dependence (Wolf et al., 1990; Havens et al., 2012).”
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    Premisecitation

    Additional factors contributing to methadone related deaths are physician error due to knowledge deficits regarding evidence based guidelines used for pain treatment, unanticipated medical and mental health comorbidites, and insurance payer policies mandating methadone as first line therapy for pain.

    “Additional factors contributing to methadone related deaths are physician error due to knowledge deficits regarding evidence based guidelines used for pain treatment, unanticipated medical and mental health comorbidites, and insurance payer policies mandating methadone as first line therapy for pain (Scanlon and Chugh, 2004; Webster et al., 2011).”
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    Study design and conductnone given

    This study examined trends in accidental overdose deaths using a national dataset of all deaths among 15-64 year olds in the US over an 11 year period.

    “This study examined trends in accidental overdose deaths using a national dataset of all deaths among 15-64 year olds in the US over an 11 year period.”
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    Study design and conductreasoning

    Confirmation of substances present through toxicology performed during an autopsy may have increased the validity of these results; however, if a person had multiple drugs in their system at death, it may have been difficult for the coroner to determine which substance predominantly contributed to death.

    “Confirmation of substances present through toxicology performed during an autopsy may have increased the validity of these results; however, if a person had multiple drugs in their system at death, it may have been difficult for the coroner to determine which substance predominantly contributed to death.”
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    Premisecitation

    American Indians/Alaska Natives aged 12 years and older reported the highest rates of substance dependence or abuse among all racial/ethnic groups examined.

    “AI/ANs aged 12 years and older reported the highest rates of substance dependence or abuse among all racial/ethnic groups examined (Substance Abuse and Mental Health Services Administration, 2004; Substance Abuse and Mental Health Services Administration, 2010).”
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    Study design and conductown data

    Our data source did not permit us to estimate how many individuals used each substance thus we were unable to calculate the death rate among users nor could we determine how common overdose was for appropriately versus inappropriately used pharmaceutical medications.

    “Our data source did not permit us to estimate how many individuals used each substance thus we were unable to calculate the death rate among users nor could we determine how common overdose was for appropriately versus inappropriately used pharmaceutical medications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The increasing pharmaceutical opioids related death rate may be attributed to an overall increase in the number of people taking pharmaceutical opioids.

    “The increasing pharmaceutical opioids related death rate may be attributed to an overall increase in the number of people taking pharmaceutical opioids.”
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    Study design and conductreasoning

    We did not examine intentional overdose deaths, i.e. suicides, or deaths of undetermined intent, because we focused on accidental, and potentially preventable, deaths.

    “We did not examine intentional overdose deaths, i.e. suicides, or deaths of undetermined intent, because we focused on accidental, and potentially preventable, deaths.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Risks associated with pharmaceutical opioid related overdose included taking high daily doses of opioids and seeking care from multiple healthcare providers to obtain many prescriptions.

    “Risks associated with pharmaceutical opioid related overdose included taking high daily doses of opioids and seeking care from multiple healthcare providers to obtain many prescriptions (Paulozzi et al., 2012; Hall et al., 2008).”
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    Premisecitation

    Doctor shopping has been associated with opioid diversion and illicit use.

    ““Doctor shopping” has also been associated with opioid diversion and illicit use (Substance Abuse and Mental Health Services Administration, 2010; Rigg et al., 2012).”
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    • cites Substance Abuse and Mental Health Services Administration, 2010

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    • cites Rigg et al., 2012

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    Premisecitation

    Rates of methadone used for addiction treatment have remained relatively stable compared to rates of methadone used for chronic pain, which have risen significantly, and mirror the increase in death rates related to methadone overdose.

    “However, rates of methadone used for addiction treatment have remained relatively stable compared to rates of methadone used for chronic pain, which have risen significantly, and mirror the increase in death rates related to methadone overdose (Substance Abuse and Mental Health Services Administration, 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Substance Abuse and Mental Health Services Administration, 2007

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Each contradiction between two passages listed here was confirmed by an independent check.

  • Highest-risk age group has two different ranges

    Minor

    The same discussion of adjusted death rates identifies the age group as 45-54 and then as 45-55. Those ranges do not describe the same group.

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Authors
Calcaterra, S., Glanz, J., & Binswanger, I. A.
Affiliations
  • Denver Health Medical Center (US)
  • Kaiser Permanente (US)
Corresponding author
Calcaterra, Susan
ORCID
Venue
Drug and Alcohol Dependence
Publisher
Elsevier BV
Published
2013-08
Volume
131
Issue
3
Pages
263-270
ISSN
0376-8716 (ISSN-L)
DOI
10.1016/j.drugalcdep.2012.11.018
PMC
PMC3935414
OpenAlex
W2074807110
Cited by
330
References
57
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 21 · 2022: 16 · 2021: 28 · 2020: 24 · 2019: 31 · 2018: 30 · 2017: 51 · 2016: 38 · 2015: 35 · 2014: 31 · 2013: 8
FWCI
38.18
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Drug and Alcohol Dependence (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Drug Abuse (R21DA031041)
  • National Institute of Allergy and Infectious Diseases (K01AI073295)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
benzodiazepines, opioid epidemic, age-adjusted death rates, demographic trends, drug overdose deaths, death certificates, ICD-10
MeSH terms
Adolescent, Adult, Cause of Death, Female, Humans, Male, Middle Aged, Naloxone, Opioid-Related Disorders, Retrospective Studies, United States, Databases, Factual, Substance-Related Disorders, Prescription Drugs, Young Adult, Drug Overdose

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