Unintended consequences: Current state of prescription opioid use and misuse in the USErin E. Krebs, MD, MPHApril 14, 2012

Disclosures 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

0100200300400500600700800

US prescription opioid sales, 1997-2007

Figure adapted from CDC Grand Rounds, 2/17/11; data source DEA ARCOS

Figure from CDC, MMWR 2011;60:1487–92

Unintended consequences

Outline Where we are

Public health harms Patient-level harms

How we got here Moving forward…strategies to reduce harm

Poisoning deaths 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 Rate: 11.9 per 100,000 overall, 9.2

unintentional Prescription drugs involved in most

poisoning deaths

Warner M et al. NCHS Data Brief #81, Dec 2011; CDC, MMWR 2011;60:1487–92 ;

Type of drug involved

UnspecifiedAny rx opioidRx, non-opioidOnly illicit

Opioid-related poisoning deaths 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 Variation in death rates

Nebraska (5.5 per 100,000) to New Mexico (27 per 100,000)

Death rates associated with prescribing volume Variation in implicated drugs

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 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

Nat’l Survey on Drug Use & Health, SAMHSA 2010

Non-medical prescription opioid use

Opioids = 5.1 million

Non-medical prescription opioid use 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 Rates of treatment admission steadily

rising 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 Retrospective cohort study of Group Health

Cooperative patients 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 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 Case-cohort study of VA patients

Included patients who received ≥ 1 opioid rx in 2004-2008 (n=155,434) Patients categorized by diagnosis

Outcome: fatal overdoses Results

Fatal overdose rate 0.04% overall Overdose death rate strongly associated with

dose Overdose cases more likely to be white, middle

aged (40-59), 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 Terminology

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 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? Not because of new evidence Increasing attention to pain

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 non-pharmacologic pain treatments

Pharmaceutical industry promotion

Pharmaceutical promotion OxyContin (oxycodone SR)

Timing of release in 1996 coincident with uptick in prescribing overall

Purdue guilty of illegal promotion practices (settlement in 2007)

Changing the conversation 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… 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 immediate-release opiates; and allowed health care providers to entertain the erroneous belief that OxyContin was less addictive than morphine.”

The fine line… 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 immediate-release opiates; and allowed health care providers to entertain the erroneous belief that OxyContin was less addictive than morphine.”

SR opioids

Promotion of selected perspectives Hypothesis: SR opioids provide more

consistent pain control and are less likely to be abused 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 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 Pain intensity fluctuates in chronic pain

Biopsychosocial explanation: Multiple factors (affect, stressors, activity) influence day-to-day experience of pain Implications: understand connections, develop

coping strategies Pharma explanation: Breakthrough pain

Implications: need for fast-acting drug (rapid-onset fentanyl currently approved for cancer pain only)

How appropriate are current prescribing patterns?

Appropriate opioid prescribing 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 Chronic pain

Prescribing when benefit unlikely Adverse patient selection

Acute pain Inappropriate indications Inappropriate course of therapy

Prescribing when benefit unlikely Back pain—most common indication for

opioids 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 Highest risk patients most likely to receive

opioids 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 Inappropriate indications

Minor injuries and illnesses Low-pain procedures

Inappropriate course of therapy Duration longer than expected course of illness Supply larger than necessary

Evidence of overprescribing Survey of postop urology patients (2010)

67% had surplus pills from original prescription Survey of Utah adults (2008)

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

Interim goals for opioid prescribing practice 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 Education

Require training on responsible opioid prescribing for DEA licensure (requires legislation)

Opioid Risk Evaluation and Mitigation Strategy (REMS) Media/public education campaign

Monitoring 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) REMS required for manufacturers of long-

acting/ER opioids (FDA, April 2011) 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 Advisory committee voted 10-25 against

REMS (July 2010) 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) Pharmacies report controlled substance

prescriptions to central database Programs are state-based

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 accessGugelmann and Perrone, JAMA 2011;306:2258-9

Limitations of PMPs Limited data to support effectiveness

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 prescribersBaehran DF et al, Ann Emerg Med. 2010;56:19-23; Paulozzi LJ et al. Pain Med. 2011;12(5):747-754

Opioid management guidelines Recommended clinical strategies: opioid

monitoring 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 Primary goal is patient centered: maximize

benefit, minimize harm for individual patient

Secondary goal: minimize possibility of collateral harm 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 Limited evidence for improved outcomes

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 usePatients 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! Questions? Comments?