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AAIM

The Prescription Drug Abuse Epidemic

Identifying patients at risk for mortality

Jeanmarie Perrone, MD, FACMTProfessor of Emergency Medicine

Director, Division of Medical ToxicologyUniversity of Pennsylvania

Lewis S. Nelson, MD, FACMTProfessor of Emergency MedicineNYU Langone School of Medicine

New York City Poison Control Center

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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

Opioid sales quadrupled1999-2010

Paulozzi L. MMWR. Nov 2011

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What is driving Rx?

• Patients exposed to the drugs “like” the drugs

• Providers are incentivized….

– “treat pain” 5th vital sign

– Patient expectations

– New beliefs about opioid safety

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

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Harrison Narcotic Act 1914

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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Physicians for Responsible Opioid Prescribing

responsibleopioidprescribing.org

Porter and Jick “Study”

• NEJM

• >11,800 patients

• Boston University Hospital

• “four” cases of addiction

Porter J, Jick H: NEJM 1980; 302:123.

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NEJM: Addiction RARE

Porter J, Jick H: NEJM 1980; 302:123.

Factor 1

• Prescribing increased as Doctors were

convinced addiction risk low

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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 Ganey/ 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 Medicine 2010:15288-92.

Formulations at higher risk?

• Is there one type of opioid more often

implicated in fatal OD?

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Formulations at higher risk?

• Methadone present in 1/3 fatalities

• Multifactorial

– Polysubstance users

– QT prolongation

– Higher doses

Factor 4

• Once initiated, hard to stop…

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Opioid sales quadrupled1999-2010

Paulozzi L. MMWR. Nov 2011

Alam A: Arch Intern Med. 2012;172(5):425-430

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Surgery Database

Alam A: Arch Intern Med. 2012;172(5):425-430

• 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).

Other challenges

• Tolerance

• Dependence

• Hyperalgesia

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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--

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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)

Primary non-heroin opiates/synthetics admission rates, by State

(per 100,000 population aged 12 and over)

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Degenardt L, et al. Addiction, 109, 90–99

Degenardt L, et al. Addiction, 109, 90–99

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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

What factors drive opioid mortalityPrescriber behaviors

• 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)

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Dunn KM, et al (2010) Ann Int Med 152:85-92

Risk of Overdose by Prescribed Opioid Dosage

among Medical Users of Opioids

Opioid dosage (mg/day)

Opioid dosage (mg/day)

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 (MMWR

2012)

– Economic benefit of methadone

– Very difficult to use

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What factors drive opioid mortalityThe drugs

• Polypharmacy, especially sedatives*

– Benzodiazepines

– Alcohol

– Sleep aids

– Antidepressants (?)

• Dose escalation phase/induction

*Paulozzi L, et al. MMWR, 2014

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What factors drive opioid mortalityUser behavior/demographics

• Broadly and imperfectly:

– Men

– Middle age

– White or Native American

– Rural areas

– Lower to middle socioeconomic

• 1999-2008 opioid mortality increased

– 415% among women and 265% among men (MMWR)

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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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What factors drive opioid mortality

• 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

http://www.nysenate.gov/files/Roundt

able-materials-1.pdf

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Opioid to heroin

• Reasons

• Epidemiology

• Studies

Cicero T, et al. N Engl J Med 2012; 367;2

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Opioid withdrawal

• Clinical findings

– “Behavioral toxicity”

– Physiological effects (HTN, tachycardia, delirium)

• Magnitude related to:

– Depth of opioid dependence

• Methadone and “round the clock” opioids

– Rate of development of withdrawal

• Natural (abstinence) vs. Precipitated (antagonist)

Kienbaum P, et al. Anesthesiology 1998;88(5):1154-61.

• µ-Opioid receptor

blockade in opioid-

dependent patients

undergoing UROD

– Profound increase in

epinephrine concentration

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Determination of Cause of Death

• Complicated

– Prescription data and PDMP data are proprietary

– ICD classification is inconsistent

– Lack of standardization in cause-of-death

terminology

• Existing numbers are an underestimate

Warner M, et al. Acad

Forensic Pathol

2013;3:231-237

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NAME project

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Death certificate