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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