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The Prescription Drug Abuse Epidemic:
Identifying Risk Before and After Death
Jeanmarie Perrone, MD, FACMTProfessor of Emergency Medicine
Director, Division of Medical Toxicology
University of Pennsylvania
Lewis S. Nelson, MD, FACMTProfessor of Emergency Medicine
Director, Fellowship in Medical Toxicology
New York University School of Medicine
What is The Epidemic?
• Deaths (27,000)
• Addiction
• 534 billion dollars
• 100 million patients with
Chronic Pain
CDC Grand Rounds: January 2012
Prescription Drugs
Chronic Pain
Two Intersecting Epidemics
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Opioid sales quadrupled1999-2010
Paulozzi L. MMWR. Nov 2011
What is driving Rx?
• Patients exposed to the drugs “like” the drugs
• Providers are incentivized….
– New beliefs about opioid safety
– “treat pain” 5th vital sign
– Patient expectations
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Eber’s Papyrus Ancient Egypt
1550 BC Poppy was used to relieve insomnia, as an anesthetic, and to deaden pain
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Bayer, 1880s
Harrison Narcotic Act 1914
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Opioid Historical Timeline
4000 1500 500 300 120 1920s 1990s 20130
AD
1860s
Opioids for pain
rarely addictive.
Eber’s Papyrus
BC
Opium wars,
morphine in
Civil war,
heroin
Opioids should be avoided
due to dependence: Ancient
Greeks
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Porter and Jick “Study”
• NEJM
• >11,800 patients
• Boston University Hospital
• “four” cases of addiction
Porter J, Jick H: NEJM 1980; 302:123.
NEJM: Addiction RARE
Porter J, Jick H: NEJM 1980; 302:123.
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Factor 1
• Prescribing increased as Doctors were
convinced addiction risk low
– 5-26% of patient on chronic opioid therapy
develop addiction
– Nearly 100% develop dependence
Boscarino JA. Addiction 2010;105:1776-1782
What factors drive opioid addiction
• Systemic issues
– Guidelines
• Pain societies and the use of opioids for CNCP
– Culture & regulatory change
• Expectations of patients and providers
• FDA limitations
– Pharma marketing
– Media coverage
IOM April 2011
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“Treat Pain” campaign
Patient Satisfaction Scores
Factor 2
• The FSMB 2004 recommends fines physicians and
hospitals for not treating pain
– received $2 million in funding from opioid manufacturers
• The JC 2001 mandated pain scores JC guidebook,
paid for by Purdue, stated, “There is no evidence that
addiction is a significant issue when persons are given opioids
for pain control.”
Pain Satisfaction Scores
Press Gainey/ HCAHPS
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Zgierska A et al. JAMA 2012 Apr 4;307:1377-8
Factor 3
Escalating doses
• As prescribing increased, patients were
prescribed these drugs RTC for chronic pain;
dependence and tolerance occurred so
escalating doses became the norm
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Risk of higher dose
• Risk estimates by opioid dose utilizing
pharmacy database in 10,000 patients
• Identified 51 OD and 6 deaths
• Risk of either increased w/ increasing dose esp
at >100 meq morphine/day
Dunn K, et al. Opioid Rx for Chronic Pain and Risk of
Overdose. Ann Intern Med 2010;152:88-92.
Dunn KM, et al. 2010 Ann Intern Med 152:85-92
Risk of Overdose by Prescribed Opioid Dosage
among Medical Users of Opioids
Opioid dosage (mg/day)
Opioid dosage (mg/day)
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Factor 4
• Once initiated, hard to stop…
Opioid sales quadrupled1999-2010
Paulozzi L. MMWR. Nov 2011
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Alam A: Arch Intern Med. 2012;172(5):425-430
Surgery Database
• Retrospective cohort opioid naïve 300,000
patients
• Patients receiving an opioid prescription
within 7 days of surgery were 44% more
likely to still receive opioid RX within 1 year
compared with those who did not (adjusted
odds ratio, 1.44; 95% CI, 1.39-1.50).
Alam A: Arch Intern Med. 2012;172(5):425-430
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Other challenges
• Tolerance
• Dependence
• Hyperalgesia
Opioid phenomenon
Opioid induced hyperalgesia: OIH
Heightened perception of pain in the absence
of disease progression or opioid withdrawal.
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Addiction rates increasing--
Primary non-heroin opiates/synthetics admission rates, by State
(per 100,000 population aged 12 and over)
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Primary non-heroin opiates/synthetics admission rates, by State
(per 100,000 population aged 12 and over)
Primary non-heroin opiates/synthetics admission rates, by State
(per 100,000 population aged 12 and over)
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Primary non-heroin opiates/synthetics admission rates, by State
(per 100,000 population aged 12 and over)
Primary non-heroin opiates/synthetics admission rates, by State
(per 100,000 population aged 12 and over)
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Primary non-heroin opiates/synthetics admission rates, by State
(per 100,000 population aged 12 and over)
Forensic Implications of
Prescription Opioids
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Unintentional Drug Overdose Mortality
Drug overdoses deaths per 100,000. Source: National Vital Statistics System. www.cdc.gov/nchs/nvss.htm.
Heroin
Cocaine
Unintentional Death: MVC vs PoisoningMMWR 2011
Why are opioids lethal?
• Opioid mortality is due almost
completely to respiratory
depression
• Reversible with:
– Assisted ventilation
– Naloxone
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Degenardt L, et al. Addiction, 109, 90–99
What factors drive opioid mortality
• There is no single answer…
• Four non-mutually-exclusive categories
– Prescriber behaviors
– The drugs themselves
– Patient behaviors & demographics
– System issues
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What factors drive opioid mortalityPrescriber behaviors (to recap)
• Prescribing opioid more often
– Quadrupled between 1980 and 2000 and still
going up
• And for weaker indications
– Chronic noncancer and neuropathic pain
• Prescribing higher doses
– Particularly for chronic pain
• Doses higher than 120 MME had greater mortality
(Gomes)
What factors drive opioid mortalityThe drugs themselves
• Extended release and long acting drugs
– 1997-2006: methadone �1177%, oxycodone
�732%, fentanyl �479%
• Methadone involved in twice as many single
drug deaths as any other opioid
– Economic benefit of methadone vs ER opioids
– Very difficult to use
Seattle Times. Methadone and the politics of pain. April 30, 2012.
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MMWR Morb Mortal Wkly Rep. 2012;61(26):493-7.
Why are ER/LA opioids so dangerous?
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What factors drive opioid mortalityThe drugs
• Dose escalation phase/induction of opioid
• Polypharmacy, especially sedatives
– Benzodiazepines
– Alcohol
– Sleep aids
– Antidepressants (?)
Paulozzi L, et al. MMWR. 2014;63(26):563-8.
What factors drive opioid mortalityUser behavior/demographics
• Broadly and imperfectly:
– Men
• 1999-2008 opioid mortality increased 415% among
women and 265% among men (MMWR)
– Middle age
– White or Native American
– Rural areas
– Lower to middle socioeconomic
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What factors drive opioid mortalityUser behavior/demographics
• Sleep apnea
• Obesity
The Joint Commission. Sentinel Event Alert: Safe Use of
Opioids in Hospitals. August 8, 2012.
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What factors drive opioid mortalityUser behavior/demographics
Webster L, et al. Sleep-Disordered Breathing and Chronic
Opioid Therapy. Pain Med 2008;9:425-432
What factors drive opioid mortalityUser behavior/demographics
• Actions
– Diversion
– Doctor shopping/pill mills
– Internet shopping minimal effect
• History of
– Substance abuse
– Chronic pain
– Psychiatric diagnosis
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Johnson H, et al. Decline in drug overdose deaths after state
policy changes – Florida, 2010-2012. MMWR 2014;63
For a view of what things were like before the policy changes, view OxyContin Express
Determination of Cause of Death
• Complicated information gathering
– Scene investigation variable by jurisdiction and
case profile
– Prescription data and PDMP data are proprietary
– ICD classification is inconsistent
• Postmortem examination not compulsory
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Davis G, et al. Acad Forensic Pathol. 2013;3:62-76
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Determination of Cause of Death
• Complicated information gathering
– Scene investigation variable by jurisdiction and
case profile
– Prescription data and PDMP data are proprietary
– ICD classification is inconsistent
• Postmortem examination not compulsory
• Laboratory interpretation complicated
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Warner M, et al. Acad Forensic Pathol 2013;3:231-237
Centralized state medical examiner
Percent of Drug Intoxication Deaths with Drugs Specific
by State and Death Investigation System, 2008-2012
Hybrid system: county coroner and ME (state and/or
county)
Existing numbers of deaths are an underestimate
Manner of Death
• Suicide is diagnosis
– Legal and other concerns
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Unintended ConsequencesHeroin
Cicero TJ, et al. N Engl J Med 2012;367:187-189.
NYC DOHMH. Epi Data Brief: Unintentional drug overdose (poisoning)
involving opioids in New York City. 2000-2013. Aug 2014.
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Unintended ConsequencesHeroin
Ameritox 2014
Some final thoughts….
• All patients with chronic pain managed with
opioids are at risk for death
– Misuse and abuse
– Dose escalation