Michael & Gary.

1. Responding to America’s Iatrogenic
Epidemic of Prescription Opioid
Addiction and Overdose
Michael R. Von Korff, ScD* and Gary Franklin, MD, MPHwz
The United States is experiencing what is arguably the greatest iatrogenic epidemic in
the history of American medicine. From 1999 to 2014, almost 200,000 prescription
opioid overdose deaths have occurred in the United States.1 Most fatal overdoses have
affected patients receiving medically prescribed opioids.2 An unprecedented decline in
life expectancy has occurred among working-age white Americans, partially attributable
to rising drug overdose deaths.3 Among the 9–11 million Americans using medically
prescribed opioids long term,4, 10%–40% of chronic opioid therapy (COT) patients may
have prescription opioid use disorder.5–7 If so, several million COT patients may now be
addicted to medically prescribed opioids. Meager evidence supports COT benefits and
safety.8 Whether analgesic efficacy is sustained long term for most COT patients has
been questioned.9 The practice of long-term opioid prescribing in the United States is
inconsistent with the basic precepts of evidence-based medicine.
LOWERING OPIOID DOSE
Bohnert et al10 shed light on one possible approach to reducing opioid overdose
risks. Confirming previous studies, they found that opioid dose predicts overdose risk.
They estimated that 60% of overdose fatalities received daily doses of 50 mg morphine
equivalent dose or greater, whereas only 25% of all COT patients received doses this
high. They did not find an unambiguous dose threshold for overdose risk—many deaths
occurred at low prescribed doses. They concluded that “lowering the recommended
dosage threshold below the 100 [morphine equivalent dose] used in many recent
guidelines would affect proportionately few patients not at risk for overdose while po-
tentially benefitting many of those at risk for overdose.” As evidence suggests that
neither high opioid dose8 nor dose escalation11 improves patient outcomes, there is a
compelling rationale for keeping COT doses low. States that have encouraged low doses
appear to have reduced opioid overdose fatalities.12,13
Surveys of COT patients find that most continue to report moderate to severe pain
and significant pain-related activity limitations, whereas only 1 in 5 report low pain
intensity with few pain-related activity limitations.14 By emphasizing patient safety,
physicians can find common ground with chronic pain patients considering COT.
Physicians can avoid unnecessary opioid prescribing and unsafe dose escalation while
working collaboratively with their patients.15,16
RESPONDING TO THE EPIDEMIC
Although limiting opioid doses of COT patients is a step in the right direction, it
is unlikely to end the current epidemic without broader actions to protect patient safety.
The last major iatrogenic epidemic of opioid addiction and overdose, in the late 19th
From the *Group Health Research Institute; wDepartments of Environmental and Occupational Health Sciences, Neurology, and Health Services, University of
Washington, Seattle; and zWashington State Department of Labor and Industries, Olympia, WA.
M.R.V.K. and G.F. serve as uncompensated board members of Physicians for Responsible Opioid Prescribing, a nonprofit organization that advocates for more
cautious and selective opioid prescribing. M.R.V.K. is the principal investigator or coinvestigator on grants to the Group Health Research Institute from
Pfizer Inc. and from the Campbell Alliance (a consortium of drug companies conducting FDA-mandated postmarketing surveillance studies of opioids) to
carry out research on the long-term use of opioid analgesics, associated risks, and patient outcomes.
Reprints: Michael R.Von Korff, ScD, Group Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101. E-mail: vonkorff.m@ghc.org.
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0025-7079/16/5405-0426
EDITORIAL
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2. century, was controlled when physicians changed their atti-
tudes in terms of opioid prescribing.17 Doctors who over-
prescribed opioids were viewed as “behind the times.”
Physicians who now believe that opioids are overprescribed
for common chronic pain conditions such as fibromyalgia,
headache, and chronic low back pain should encourage more
cautious and selective opioid prescribing by their colleagues
and through their professional societies, similar to the recent
position paper of the American Academy of Neurology.18
The prescription opioid addiction and overdose epidemic
emerged over 2 decades. To address this epidemic, we pro-
pose 3 immediate actions to reduce initiation of in-
appropriate COT:
(1) Avoid ill-advised and unplanned initiation of COT: The
number of patients initiating long-term opioid use can be
reduced by more selective and cautious initial prescrib-
ing. Clinicians should limit prescribing narcotics to the
most severe acute pain. When opioids are indicated,
clinicians should limit the number of pills initially
prescribed (10 or fewer pills is usually sufficient).
Prescription Drug Monitoring Program (PDMP) data
should be consistently checked. Patients should be
explicitly informed that opioids are for time-limited
use. Among injured workers with acute low back pain,
those who received just 2 prescriptions or 7 days of
opioids were twice as likely to be disabled 1 year
later.19Beyond initial use, before considering refills,
clinicians should carefully consider whether decisive
benefits are being realized and whether there are early
warning signs of addiction. Too often, patients are
physically and/or psychologically dependent on opioids
before doctor and patient consider whether COT is an
appropriate option. Patients should be fully informed of
the significant risks involved. After-the-fact assent to
unplanned long-term opioid use is not appropriate.
Unfortunately, initiation of long-term opioid use is more
often than not unplanned20 and COT patients are often
inadequately informed of addiction and overdose risks.-
Many COT patients prefer intermittent opioid use at low
doses, offering more control over the timing of opioid
use and reducing risks of tolerance, physical dependence,
and side-effects. As time-scheduled use of long-acting
opioids increases opioid dose, it may also increase
overdose risks. There is no evidence that time-scheduled
opioid regimens with extended-release formulations
reduce addiction risks.
(2) Change policies and regulations: The historical record
suggests that unsubstantiated claims were made in terms
of COT safety. For example, the 1996 consensus
statement of the American Academy of Pain Medicine
and the American Pain Society on the use of opioids for
chronic pain21 concluded that:
The trend is to adopt laws or guidelines that specifically
recognize the use of opioids to treat intractable pain. These
statementsy help clarify that the use of opioids for the relief
of chronic pain is a legitimate medical practice.
Misunderstanding of addiction and mislabeling of patients as
addicts result in unnecessary withholding of opioid medi-
cations.
For most opioids, there does not appear to be an arbitrary
upper dosage limit.
Respiratory depression induced by opioids tends to be a
short-lived phenomenon, generally occurs only in the opioid-
naive patient, and is antagonized by pain.
Assertions such as these, not supported by scientific
evidence, were used in “model” opioid regulatory policies,
leading 20 states to adopt policies and regulations that
made it difficult for state medical boards to control high-dose
opioid prescribing. State policies that impair clinically
appropriate regulation of opioid prescribing should be
repealed in all states and replaced with updated principles
that reflect what has been learned about the risks of addiction
and overdose. Revised guidelines, policies, and regulations
should be based in newer state guidelines and the forth-
coming Center for Disease Control and Prevention (CDC)
guidelines. At the same time, federal, state, and private
health insurance reimbursement policies need to be changed
to make safer and more effective nonopioid treatments for
chronic pain more widely available and accessible, including
multimodal pain management programs and distance con-
sultation and training services for chronic pain patients in
rural areas.
(3) Considerably enhance population surveillance of opioid
prescribing and safety: The Food and Drug Adminis-
tration’s (FDA’s) recently mandated postmarketing
surveillance program for extended-release opioids needs
to be extended to the larger number of COT patients
using immediate-release opioids. Using methods already
developed for assessing prescription opioid misuse and
addiction, the prevalence of prescription opioid use
disorder and opioid misuse among COT patients could
be determined by a survey of representative COT
patients from diverse practice settings. This could clarify
how common opioid addiction and misuse are among
patients using opiods long term. If a large percentage of
COT patients have a prescription opioid use disorder,
then untested assumptions on the relative benefits and
risks of COT will need to be reconsidered.Population
surveillance initiatives on opioid prescribing and safety
of the CDC, FDA, and National Institute on Drug Abuse
can be better coordinated. Large pharmacovigilance
databases developed for FDA studies and state PDMP
data can be used to assess opioid-related risks of
addiction, overdose, and other adverse health effects.
The drug abuse surveys and surveillance systems of the
CDC and National Institute on Drug Abuse have already
made enormous contributions toward clarifying opioid-
related risks. As there is not a strong evidence base for
initiatives to reduce opioid risks among COT patients,
population surveillance and available electronic data-
bases need to be used strategically to guide changes in
opioid prescribing. Surveillance of opioid prescribing
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3. trends in states and health plans could determine whether
changes are accompanied by reductions in opioid-related
morbidity and mortality as well as assessing effects on
patient-reported chronic pain outcomes. For example, a large
proportion of overdose deaths are in Medicaid programs,
regulated by both states and the Center for Medicare and
Medicaid Services. Steps should be taken to monitor changes
in opioid prescribing and progress in reducing opioid
overdose mortality in Medicaid populations.COT patients
already physically and/or psychologically dependent on long-
term opioid use cannot be abandoned as medical opinion on
the role of opioids in long-term chronic pain care shifts. We
propose 3 additional actions to protect chronic pain patients
currently using opioids long term.
(4) Step up clinical monitoring: If risks of addiction and
serious opioid misuse are high among COT patients,5–8
then prescribing opioids long term without close
monitoring is ill-advised. Close monitoring of whether
patients are deriving benefit, misusing drugs, or becom-
ing addicted to opioids should include checking PDMP
data and random urine drug screening guided by risk. In
addition, clinicians need to ask direct, nonjudgmental
questions about prescription opioid use disorder (eg,
opioid craving/preoccupation, loss of control, opioid-
related harms, unsuccessful efforts to quit or cut-back).
Assessment of opioid addiction should not be left to
guesswork when patients and family members can be
asked direct questions about opioid-related problems.
Patients are often willing to report opioid-related
problems when asked.5,6At every prescribing visit, the
total daily morphine equivalent dose (estimated by an
online conversion calculator), as well as pain severity
and pain interference with function and quality of life
(assessed by 3 item scale) should be documented. For
patients whose function is poor and pain inadequately
controlled, tapering off opioids should be carefully
considered. Unfortunately, monitoring of long-term
opioid use is usually sporadic.22 As many clinicians do
not check PDMP data, some states have passed
legislation requiring PDMP checks. Other states have
made technological enhancements to PDMP systems to
facilitate use of PDMP data in routine patient care.
(5) Consistently offer taper as an option: Even among the
subset of COT patients who find opioids helpful for
controlling pain, almost half state that they would like to
cut down their dose or quit completely.23 Clinicians
should consistently offer a trial of a gradual taper off
opioids or to a lower dose as an option. Many patients
are afraid of tapering because they are fearful that their
pain will worsen. Experience with gradual tapers
suggests that pain usually does not worsen, and function
often improves.24 Patient-physician trust and collabora-
tion are essential in caring for patients struggling to
manage chronic pain. Skilled clinicians have achieved
success in supporting patients tapering off opioids or in
transitioning to medication-assisted addiction treatment
when indicated.
(6) Ensure treatment options for addicted COT patients:
Addicted COT patients unable or unwilling to gradually
taper off opioids should be offered addiction treatment,
including medication-assisted therapy. Buprenorphine
treatment, which can reduce overdose risks, needs to be
much more widely available. It can also provide a safer
option for patients who feel that pain is unmanagable
without opioids. Costs of medication-assisted addiction
treatment (including drugs and physician training/
certification to ensure widespread availability) might be
defrayed by state taxes on opioid analgesics. As societal
costs of prescription opioid addiction are directly linked
to opioid analgesic sales, it would be appropriate to tax
opioid analgesics to ensure accessibility of urgently
needed addiction treatments.
Unsubstantiated claims misled a generation of physi-
cians into believing that COT could be prescribed without
untoward risks of addiction and overdose among chronic
pain patients. They led many physicians to believe that
chronic pain patients are benefited by long-term opioid use
more than data and clinical experience suggest.25 Two dec-
ades later, claims that opioids are effective for long-term use
among chronic pain patients remain unproven, whereas ep-
idemiologic data have shown significant harms.8 We are
facing the worst man-made epidemic in modern medical
history. Iatrogenic drug addiction and overdose have resulted
from well-intentioned but ill-advised efforts to care for
chronic pain patients by indiscriminate long-term prescribing
of opioid analgesics. We need health care leaders, state and
Federal regulatory bodies, and professional societies to act
immediately and forcefully to address this epidemic.
REFERENCES
1. Jones CM. The opioid epidemic: overview and a look to the future.
Conference Presentation, Evidence-based Primary Pain Care: A New
Opioid Guideline From Washington State, Seattle, WA, June 12, 2015.
2. Johnson EM, Lanier WA, Merrill RM, et al. Prescription opioid-related
overdose deaths: description of decedents by next of kin or best contact,
Utah, 2008–2009. J Gen Intern Med. 2013;28:522–529.
3. Case A, Deaton A. Rising morbidity and mortality in midlife among
white non-Hispanic Americans in the 21st
century. Proc Natl Acad Sci.
2015;112:15078–15083. Available at: http://www.pnas.org/cgi/doi/
10.1073/pnas.1518393112. Accessed March 24, 2016.
4. Boudreau D, Von Korff M, Rutter CM, et al. Trends in long-term opioid
therapy for chronic pain. Pharmacoepidemiol Drug Saf. 2009;18:
1166–1175.
5. Boscarino JA, Hoffman SN, Han JJ. Opioid-use disorder among patients
on long-term opioid therapy: impact of final DSM-5 diagnostic criteria
on prevalence and correlates. Subst Abuse Rehabil. 2015;6:83–91.
6. Degenhardt L, Bruno R, Lintzeris N, et al. Agreement between
definitions of pharmaceutical opioid use disorders and dependence in
people taking opioids for chronic non-cancer pain (POINT): a cohort
study. Lancet Psychiatry. 2015;2:314–322.
7. Palmer RE, Carrell DS, Cronkite D, et al. The prevalence of problem
opioid use in patients receiving chronic opioid therapy: computer-
assisted review of electronic health record clinical notes. Pain. 2015;
156:1208–1214.
8. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of
long-term opioid therapy for chronic pain: a systematic review for a
National Institutes of Health Pathways to Prevention Workshop
effectiveness and risks of long-term opioid therapy for chronic pain.
Ann Intern Med. 2015;162:276–286.
9. Ballantyne JA. “Safe and effective when used as directed”: the case of
chronic use of opioid analgesics. J Med Toxicol. 2012;8:417–423.
10. Bohnert A, Logan JE, Ganoczy D, et al. A detailed exploration into the
association of prescribed opioid dosage and overdose deaths among
patients with chronic pain. Med Care. 2016;54:435–441.
Editorial Medical Care Volume 54, Number 5, May 2016
428 | www.lww-medicalcare.com Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.

4. 11. Naliboff BD, Wu SM, Schieffer B, et al. A randomized trial of 2
prescription strategies for opioid treatment of chronic nonmalignant
pain. J Pain. 2011;12:288–296.
12. Franklin GM, Mai J, Turner J, et al. Bending the prescription opioid
dosing and mortality curves: impact of the Washington State opioid
dosing guideline. Am J Ind Med. 2012;55:325–331.
13. Paone D, Tuazon E, Kattan J, et al. Decrease in rate of opioid analgesic
overdose deaths—Staten Island, New York City, 2011-2013. Morb
Mortal Wkly Rep. 2015;64:491–494.
14. LeResche LA, Saunders K, Dublin S, et al. Sex and age differences in
global pain status among patients using opioids long term for chronic
noncancer pain. J Womens Health. 2015;24:629–635.
15. Trescott CE, Beck RM, Seelig MD, et al. Group Health’s initiative to
avert opioid misuse and overdose among patients with chronic
noncancer pain. Health Aff (Millwood). 2011;30:1420–1424.
16. Von Korff M, Dublin S, Walker RL, et al. The impact of opioid risk
reduction initiatives on high-dose opioid prescribing for patients on
chronic opioid therapy. J Pain. 2016;17:101–110.
17. Courtwright DT. Preventing and treating narcotic addiction: a century of
federal drug control. N Engl J Med. 2015;373:2095–2097.
18. Franklin GM. Opioids for chronic noncancer pain. A position paper of
the American Academy of Neurology. Neurology. 2014;83:1277–1284.
19. Franklin GM, Stover BD, Turner JA, et al. Early opioid prescription and
subsequent disability among works with back injuries. The Disability
Risk Identification Study Cohort. Spine. 2008;33:199–204.
20. Von Korff M, Turner JA, Shortreed SM, et al. Timeliness of care
planning upon initiation of chronic opioid therapy for chronic pain. Pain
Med. 2016;17:511–520.
21. American Academy of Pain Management and American Pain Society.
The use of opioids for the treatment of chronic pain: a consensus
statement from the American Academy of Pain Medicine and the
American Pain Society. 1996. Available at: http://www.jpain.org/article/
S1082-3174(97)80022-0/pdf. Accessed February 19, 2016.
22. Krebs EE, Ramsey DC, Miloshoff JM, et al. Primary care monitoring of
long-term opioid therapy with chronic pain. Pain Med. 2011;12:
740–746.
23. Howe CQ, Sullivan MD, Saunders K, et al. Depression and ambivalence
toward chronic opioid therapy for chronic pain. Clin J Pain. 2012;28:
561–566.
24. Cunningham JL, Evans MM, King SM, et al. Opioid tapering in
fibromyalgia patients: experience from an interdisciplinary pain
rehabilitation program. Pain Med. 2016;pii:pnv079.
25. Katz MH. Long-term opioid treatment of nonmalignant pain: a believer
loses his faith. Arch Intern Med. 2010;170:1422–1424.
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