24/09/2014
1
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
24/09/2014
2
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
24/09/2014
3
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
24/09/2014
4
24/09/2014
5
Bayer, 1880s
24/09/2014
6
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
24/09/2014
7
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.
24/09/2014
8
NEJM: Addiction RARE
Porter J, Jick H: NEJM 1980; 302:123.
Factor 1
• Prescribing increased as Doctors were
convinced addiction risk low
24/09/2014
9
“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
24/09/2014
10
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
24/09/2014
11
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?
24/09/2014
12
Formulations at higher risk?
• Methadone present in 1/3 fatalities
• Multifactorial
– Polysubstance users
– QT prolongation
– Higher doses
Factor 4
• Once initiated, hard to stop…
24/09/2014
13
Opioid sales quadrupled1999-2010
Paulozzi L. MMWR. Nov 2011
Alam A: Arch Intern Med. 2012;172(5):425-430
24/09/2014
14
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
24/09/2014
15
Opioid phenomenon
Opioid induced hyperalgesia: OIH
Heightened perception of pain in the absence
of disease progression or opioid withdrawal.
24/09/2014
16
Addiction rates increasing--
24/09/2014
17
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)
24/09/2014
18
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)
24/09/2014
19
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)
24/09/2014
20
Degenardt L, et al. Addiction, 109, 90–99
Degenardt L, et al. Addiction, 109, 90–99
24/09/2014
21
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)
24/09/2014
22
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
24/09/2014
23
What factors drive opioid mortalityThe drugs
• Polypharmacy, especially sedatives*
– Benzodiazepines
– Alcohol
– Sleep aids
– Antidepressants (?)
• Dose escalation phase/induction
*Paulozzi L, et al. MMWR, 2014
24/09/2014
24
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)
24/09/2014
25
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
24/09/2014
26
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
24/09/2014
27
Opioid to heroin
• Reasons
• Epidemiology
• Studies
Cicero T, et al. N Engl J Med 2012; 367;2
24/09/2014
28
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
24/09/2014
29
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
24/09/2014
30
NAME project
24/09/2014
31
Death certificate
