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Unintended consequences:
Current state of prescription
opioid use and misuse in the US
Erin E. Krebs, MD, MPH
April 14, 2012
Disclosures
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I have no commercial financial relationships to disclose
My work is supported by the Department of Veterans Affairs
(VA)
Views expressed in this presentation are mine and do not
reflect the position or policy of the VA or the US government
Trends in opioid use
US prescription opioid sales, 1997-2007
800
700
600
500
400
300
200
100
0
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Figure adapted from CDC Grand Rounds, 2/17/11; data source DEA ARCOS
Unintended consequences
Figure from CDC, MMWR 2011;60:1487–92
Outline
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Where we are
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Public health harms
Patient-level harms
How we got here
Moving forward…strategies to reduce harm
Poisoning deaths
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Poisoning is now #1 cause of injury death (2008)
Warner M et al. NCHS Data Brief #81, Dec 2011; CDC, MMWR 2011;60:1487–92 ;
Drug poisoning deaths
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Rate: 11.9 per 100,000 overall, 9.2 unintentional
Prescription drugs involved in most poisoning deaths
Type of drug involved
Unspecified
Any rx opioid
Rx, non-opioid
Only illicit
Warner M et al. NCHS Data Brief #81, Dec 2011; CDC, MMWR 2011;60:1487–92 ;
Opioid-related poisoning deaths
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Half of opioid-related overdoses involve another drug
(benzodiazepines most common)
Type of opioid involved in deaths
Warner M et al. NCHS Data Brief #81, Dec 2011
Overdose deaths vary among states
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Variation in death rates
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Nebraska (5.5 per 100,000) to New Mexico (27 per 100,000)
Death rates associated with prescribing volume
Variation in implicated drugs
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Florida (2009): oxycodone (6.4 per 100,000), alprazolam (4.4),
methadone (3.9)
Washington (2004-07): methadone (64% of deaths),
oxycodone (23%), hydrocodone (14%)
Warner M et al. NCHS Data Brief #81, Dec 2011; CDC, MMWR 2011;60:1487–92 ;
Demographics of opioid-related death
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45-54 year age group (next highest is 35-44)
Male > female
Non-Hispanic white and Native > other groups
Similar to demographics of non-medical prescription
drug use
Warner M et al. NCHS Data Brief #81, Dec 2011; CDC, MMWR 2011;60:1487–92
Non-medical prescription opioid use
Opioids = 5.1 million
Nat’l Survey on Drug Use & Health, SAMHSA 2010
Non-medical prescription opioid use
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20% of HS students ever used an rx drug (2009)
CDC, Youth Risk Behavior Surveillance—US, 2009; SAMHSA, Nat’l Survey on Drug Use & Health,
2010; SAMHSA. Treatment Episode Data Set (TEDS): 1998-2008.
Prescription opioid addiction
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Rates of treatment admission steadily rising
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1998: 9 per 100,000 aged 12 and older
2008: 45 per 100,000
CDC, Youth Risk Behavior Surveillance—US, 2009; SAMHSA, Nat’l Survey on Drug Use & Health,
2010; SAMHSA. Treatment Episode Data Set (TEDS): 1998-2008.
What about patients with chronic
pain?
Opioid-related overdose among patients
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Retrospective cohort study of Group Health
Cooperative patients
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Included patients with chronic pain and no cancer diagnosis
who received ≥ 3 opioid rx within 90 days (n=9960)
Outcomes: fatal and non-fatal overdoses
Records reviewed to confirm overdose codes
Results
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Overall overdose rate 148/100,000 person-years
78% of all overdose events were “serious”
Overdose strongly associated with daily dose (1.8% annual
rate in 100 Meq mg/day group)
Dunn KM et al, Ann Intern Med. 2010;152:85-92
Overdose deaths among patients
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Case-cohort study of VA patients
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Included patients who received ≥ 1 opioid rx in 2004-2008
(n=155,434)
 Patients categorized by diagnosis
Outcome: fatal overdoses
Results
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Fatal overdose rate 0.04% overall
Overdose death rate strongly associated with dose
Overdose cases more likely to be white, middle aged (4059), have substance use disorders, psychiatric disorders, and
acute or chronic pain
Bohnert ASB et al, JAMA. 2011;305(13):1315-1321
Addiction in pain patients
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Terminology
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Addiction: meeting DSM criteria for substance dependence
Misuse: behaviors that may or may not indicate a substance
use disorder
Misuse very common in primary care
Until recently, addiction was thought to be rare
Noble M et al, Long-term opioid management for chronic noncancer pain. Cochrane Review, 2010
Addiction in pain patients
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Prospective study of patients receiving daily opioids for ≥3
months in primary care (n=801)
 Patients recruited from primary care clinic for in-person
interview and UDT (response rate = 78%)
 3.1% opioid dependence, 9.7% any substance use disorder
 24% positive urine tox (46% previously denied)
Telephone survey of Geisinger patients who received ≥4
opioid rx in 12 months (n=705)
 Patients identified through medical records and contacted by
telephone for diagnostic interview (response rate = 33%)
 Results: 25.8% opioid dependence
Fleming MF et al, J Pain, 2007;7:573-582; Boscarino JA et al, Addiction, 2010;105:1776–1782
How did we get here?
Why are we prescribing more opioids?
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Not because of new evidence
Increasing attention to pain
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Chronic pain as a disease (not just a symptom)
Application of palliative care principles to chronic pain
Emphasis on pain measurement
Limited awareness of and access to nonpharmacologic pain treatments
Pharmaceutical industry promotion
Pharmaceutical promotion
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OxyContin (oxycodone SR)
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Timing of release in 1996 coincident with uptick in
prescribing overall
Purdue guilty of illegal promotion practices (settlement in
2007)
Changing the conversation
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Supporting Joint Commission pain assessment standards
Emphasizing pharmacologic pain management
Promoting selected perspectives
 Effectiveness/safety of sustained release (SR) opioids
 Breakthrough pain in chronic pain
The fine line…
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FDA press release (2007): “Purdue trained its sales
representatives to make false representations to health care
providers about the difficulty of extracting oxycodone, the
active ingredient, from the OxyContin tablet; trained its sales
force to represent to health care providers that OxyContin
did not cause euphoria and was less addictive than immediaterelease opiates; and allowed health care providers to entertain
the erroneous belief that OxyContin was less addictive than
morphine.”
The fine line…
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FDA press release (2007): “Purdue trained its sales
representatives to make false representations to health care
providers about the difficulty of extracting oxycodone, the
active ingredient, from the OxyContin tablet; trained its sales
SR opioids
force to represent to health care providers that OxyContin
did not cause euphoria and was less addictive than immediaterelease opiates; and allowed health care providers to entertain
the erroneous belief that OxyContin was less addictive than
morphine.”
Promotion of selected perspectives
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Hypothesis: SR opioids provide more consistent pain
control and are less likely to be abused
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Systematic review of long-acting vs. short-acting opioids
 No evidence of improved analgesia or lower AE rates
 No data comparing rates of addiction or abuse
Potential consequences
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Increase in SR opioids has outpaced overall increase
Long-acting opioid use is associated with higher doses
Carson S et al. Drug class review: Long-acting opioid analgesics. Oregon Drug Effectiveness Review
Project, 2010
Promotion of selected perspectives
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Pain intensity fluctuates in chronic pain
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Biopsychosocial explanation: Multiple factors (affect,
stressors, activity) influence day-to-day experience of pain
 Implications: understand connections, develop coping
strategies
Pharma explanation: Breakthrough pain
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Implications: need for fast-acting drug (rapid-onset fentanyl
currently approved for cancer pain only)
How appropriate are current
prescribing patterns?
Appropriate opioid prescribing
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Hard to define—no consensus on appropriate role of opioid
therapy, especially in chronic pain
American Pain Society/American Academy of Pain Medicine
guidelines for opioid therapy in chronic pain
 25 recommendations: none based on strong evidence; 4 on
moderate evidence
Chou R et al, J Pain 2009;10(2): 113-130; Chou R et al, J Pain 2009;10(2): 147-159
Potentially inappropriate prescribing
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Chronic pain
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Prescribing when benefit unlikely
Adverse patient selection
Acute pain
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Inappropriate indications
Inappropriate course of therapy
Prescribing when benefit unlikely
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Back pain—most common indication for opioids
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Systematic review in chronic back pain (Martell et al, 2007)
 Meta-analysis of 4 trials, duration 1-16 weeks
 Results: No difference between opioid and control
Headache
Fibromyalgia
Martell BA et al, Ann Intern Med 2007;146:116-127. Deshpande A et al, Cochrane review, 2010
“Adverse selection” for opioid therapy
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Highest risk patients most likely to receive opioids
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Depression and anxiety disorders
Alcohol and drug use disorders
Smoking
Multiple co-existing pain conditions or sites
Among patients using long-term opioids, highest risk
patients receive highest risk regimens
Sullivan MD et al, Pain 2010;151:567–568; Stover BD et al, J Pain 2006;7:718-725; Edlund MJ et al, J
Pain Symptom Manage 2010;40:279–89.; Morasco BJ et al, Pain 2010;151:625–32
Overprescribing for acute pain
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Inappropriate indications
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Minor injuries and illnesses
Low-pain procedures
Inappropriate course of therapy
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Duration longer than expected course of illness
Supply larger than necessary
Evidence of overprescribing
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Survey of postop urology patients (2010)
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67% had surplus pills from original prescription
Survey of Utah adults (2008)
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21% filled at least one opioid prescription in prior 12 mos
72% had leftover medication (25% disposed of them)
Bates et al. J Urology 2010;185:551-5; CDC, MMWR. 2010;59:153-157
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Interim goals for opioid prescribing practice
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Reduce overuse, ineffective use, and high-risk prescribing
Improve prescribing practice to minimize harms
Strategies to minimize harms
http://www.whitehouse.gov/ondcp/prescription-drug-abuse
Obama administration plan
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Education
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Monitoring
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Require training on responsible opioid prescribing for DEA
licensure (requires legislation)
Opioid Risk Evaluation and Mitigation Strategy (REMS)
Media/public education campaign
Enhance state prescription monitoring programs (PMPs)
Authorize VA/DoD to participate (legislation passed)
Medication disposal: establish DEA rules
Enforcement: target pill mills, criminal prescribers,
doctor-shoppers
http://www.whitehouse.gov/ondcp/prescription-drug-abuse
Risk Evaluation and Mitigation (REMS)
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REMS required for manufacturers of long-acting/ER
opioids (FDA, April 2011)
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Prescriber education
 Developed by manufacturer or CME provider
 Voluntary for prescribers
Patient education
 Medication guides on safe use, storage, disposal
http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm
Limitations of REMS
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Advisory committee voted 10-25 against REMS (July
2010)
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REMS should apply to all opioids
More robust public health campaign needed
 Educational interventions have minimal effects on behavior
 Limited evidence, disagreement among experts on
appropriate place of opioids in chronic pain
Prescriber participation should be mandatory
Better data and tracking needed
http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm163647.htm
Prescription monitoring programs (PMP)
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Pharmacies report controlled substance prescriptions
to central database
Programs are state-based
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44 states have legislation, 34 have operational programs
California’s program was first (est. 1939)
 Electronic monitoring system established in 1996
Features vary
 Available to prescribers and/or law enforcement
 Proactive: unsolicited reports to prescribers
 Web-based real-time access
Gugelmann and Perrone, JAMA 2011;306:2258-9
Limitations of PMPs
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Limited data to support effectiveness
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Retrospective study comparing US states, 1999-2005
 Evaluated effects of operational PMP (n=19) & use of
proactive reporting (n=13) on mortality and prescribing
 Overdose rates increased in all states
 Prescribed MEq mg increased in all states
 No significant differences by PMP status
Prospective survey in Ohio ED: PMP data changed prescribing
plan in 41% of cases
Major problem: underused by prescribers
Baehran DF et al, Ann Emerg Med. 2010;56:19-23; Paulozzi LJ et al. Pain Med. 2011;12(5):747754
Opioid management guidelines
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Recommended clinical strategies: opioid monitoring
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Opioid agreements (“narcotic contracts”)
Assessment of pain, pain-related function, progress towards
personal goals
Assessment of adverse effects
Assessment of adherence
 Medication use (how, when, and why)
 Urine drug testing (UDT)
 Prescription drug program review
Chou R et al (APS/AAPM Guidelines), J Pain 2009;10(2): 113-130;VA/DoD Clinical Practice
Guidelines, 2010
Goals of opioid monitoring
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Primary goal is patient centered: maximize benefit,
minimize harm for individual patient
Secondary goal: minimize possibility of collateral harm
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70% of non-medical rx drug users get them from a friend or
relative
Deshpande, Cochrane review, 2010; Noble, Cochrane review, 2010; Nuesch, Cochrane review, 2010; Martell,
Ann Intern Med 2007; SAMHSA, Nat’l Survey on Drug Use & Health, 2008
Limitations of opioid monitoring
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Limited evidence for improved outcomes
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Systematic review: (2010) “weak” support for UDT and
opioid agreements
But some practices well supported by indirect evidence
 UDT provides actionable information
 Physicians cannot accurately predict drug use
 Patients underreport drug use and opioid misuse
Underlying deficiencies in pain management training
and services
Barriers to implementation in primary care
Starrels J et al, Annals Intern Med 2010
Thank you!
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Questions? Comments?