Development of the Centers for Disease Control and Prevention Opioid Prescribing Guidelines for Chronic Pain in Primary Care

1. Development of the CDC
Opioid Prescribing Guidelines
for Chronic Pain in Primary Care
Presenters:
• Tamara Haegerich, PhD, Deputy Associate Director for
Science, Division of Unintentional Injury Prevention, CDC
• Deborah Dowell, MD, MPH, Senior Medical Advisor, Division
of Unintentional Injury Prevention, CDC
Clinical Track
Moderator: Mark D. Birdwhistell, MPA, Vice President
for Administration and External Affairs, University of
Kentucky HealthCare

2. Disclosures
• Deborah Dowell, MD, MPH, has disclosed no relevant, real or
apparent personal or professional financial relationships with
proprietary entities that produce health care goods and
services.
• Tamara Haegerich, PhD, has disclosed no relevant, real or
apparent personal or professional financial relationships with
proprietary entities that produce health care goods and
services.
• Mark D. Birdwhistell, MPA, has disclosed no relevant, real or
apparent personal or professional financial relationships with
proprietary entities that produce health care goods and
services.

3. Disclosures
• All planners/managers hereby state that they or their
spouse/life partner do not have any financial
relationships or relationships to products or devices
with any commercial interest related to the content of
this activity of any amount during the past 12 months.
• The following planners/managers have the following to
disclose:
– John J. Dreyzehner, MD, MPH, FACOEM – Ownership
interest: Starfish Health (spouse)
– Robert DuPont – Employment: Bensinger, DuPont &
Associates-Prescription Drug Research Center

4. Learning Objectives
1. Outline the new CDC guideline for prescribing
opioid pain relievers for chronic pain in primary
care settings.
2. Describe the evidence and development process
behind the CDC guideline.
3. Explain the potential benefits of implementing
CDC’s recommendations to promote safer use of
opioids in clinical practice and improve patient
outcomes and public health.
4. Provide accurate and appropriate counsel as
part of the treatment team.

5. Development of the CDC Opioid
Prescribing Guideline for Chronic
Pain in Primary Care
Deborah Dowell, MD, MPH
Tamara Haegerich, PhD
Division of Unintentional Injury Prevention
National Center for Injury Prevention and Control
Centers for Disease Control and Prevention

6. BACKGROUND AND METHODS

7. Background and need
• 11% of Americans experience daily (chronic) pain
• Opioids frequently prescribed for chronic pain
• Primary care clinicians
 account for ~50% of opioid pain medications dispensed
 report concern about opioids and insufficient training
• >165,000 rx opioid-related overdose deaths since 1999
• About 2 million people abused or were dependent in 2013
• Existing national guidelines were published in 2010 or earlier
and do not incorporate new evidence published since 2010

8. Primary audience
• Primary care clinicians (e.g., family physicians, internists)
treating patients > 18 years with chronic pain (i.e., lasting
> 3 months or past time of normal tissue healing) in
outpatient settings outside of active cancer treatment,
palliative care, and end- of-life care

9. CDC Draft Recommendations
Core Expert Group
Consultation
Constituent Input
(Webinar)
NCIPC Advisory
Committee
CDC Draft Guideline
FRN Public
Comment
Federal Partner
Review
Peer
Review
Core Expert and
Stakeholder Review
Systematic Literature Review
CDC Revised Guideline
Overview of the development process

10. GRADE Methodology
• Updated 2014 AHRQ-sponsored review
• Identified key clinical questions
– KQ1: Effectiveness of long-term opioid therapy
– KQ2: Harms and adverse events
– KQ3: Effectiveness of methods for initiation, titration, dosing
– KQ4: Accuracy of risk prediction instruments and effectiveness of risk
mitigation strategies
– KQ5: Effects of prescribing for acute pain on long-term use
• Categorized type (quality) of evidence
– Type 1: RCTs; overwhelming observational studies
– Type 2: RCTs (limitations); strong observational
– Type 3: RCTs (notable limitations); observational
– Type 4: RCTs (major limitations); observational (notable limitations)
clinical experience

11. GRADE Methodology
• Conducted supplemental contextual evidence review
– Benefits and harms
– Provider and patient values and preferences
– Resource allocation (cost)
– Effectiveness of alternative treatments
• Drafted recommendations
• Applied strength of recommendation categories
– A: applies to all patients; most patients should receive
recommended course of action
– B: individual decision making required; providers help
patients arrive at decision consistent with
values/preferences and clinical situation

12. CLINICAL EVIDENCE REVIEW

13. KQ1: Effectiveness
• No study of opioid therapy vs. placebo, no opioid
therapy, or non-opioid therapy for chronic pain evaluated
long-term (>1 year) outcomes related to pain, function,
or quality of life
• Most placebo-controlled trials < 6 weeks*
– Opioids more effective than placebo for nociceptive and
neuropathic pain
– Small to moderate effect sizes
– High percentage discontinued long-term use because of
lack of efficacy and adverse events
* short-term studies not re-reviewed

14. KQ2: Abuse, addiction, misuse
• 10 non-comparative studies; Variations in definitions and
methods for assessment
• Primary care: dependence 3% to 26%
• Pain clinics: addiction 2% to 14%

15. KQ2: Overdose
• 1 retrospective cohort study: chronic pain patients in US
health system; recent opioid use associated with increased
risk of:
– Any overdose event (adjusted HR 5.2, 95% CI 2.1 to 2.5)
– Serious overdose event (adjusted HR 8.4, 95% CI 2.5 to 2.8)
– Dose-dependent association
• 1 case-control study: dose-dependent association with risk of
overdose (relative to 1 to 19 MME/day . . .)
– 20 to 49 MME/day: 1.92
– 50 to 99 MME/day: 2.04
– 100 to 199 MME/day: 2.88
– > 200 MME/day: 2.88

16. KQ2: Dose-dependent effects
• Higher doses associated with
– Overdose (2 studies)
– Abuse or dependence diagnosis (1 study)
– Fractures (2 studies)
– Cardiovascular events (2 studies)
– Endocrinologic adverse events (2 studies)
– Motor vehicle crashes (1 study)
• No evidence on dose-dependent effects on pain or
function

17. KQ3: Initiation and titration
• 4 studies (RCTs and cohort): Inconsistent results and
differences in dosing protocols and opioid doses
• New large VA cohort study
– Initiation with long-acting opioid vs short-acting
associated with increased risk of overdose (adjusted
HR 2.33, 95% CI 1.26 to 4.32)
– Greatest risk in first 2 weeks

18. KQ3: Comparative effectiveness and
harms of long-acting opioids
• 6 studies (RCTs and cohort): Inconsistent results
regarding differences between long-acting opioids
– Risks may vary in different settings as a function of
monitoring and management protocols
• New TN Medicaid cohort study
– Methadone associated with higher mortality risk
compared to sustained-release morphine (HR 1.46,
95% CI 1.17 to 1.83)

19. K3: Dose escalation vs maintenance
• 1 RCT in VA patients with musculoskeletal pain
• No differences in pain, function, or use of nonopioid
medications or physical therapy after 12 months
– Limited separation between groups in doses (mean 52
MME/day vs 40 MME/day)

20. KQ4: Accuracy of risk prediction
• 5 studies with inconsistent estimates and methodological
shortcomings
– Opioid Risk Tool (ORT)
– Screener and Opioid Assessment for Patients with
Pain-Revised (SOAPP-R)
– Brief Risk Interview
• Based on sensitivity and specificity, insufficient accuracy
for classification of patients

21. KQ5: Effects of opioid therapy for
acute pain on long-term use
• 2 retrospective cohort studies
– Low risk surgery: use of opioids within 7 days
associated with increased likelihood of use at 1 year
(adjusted OR 1.44, 95% CI 1.39 to 1.50)
– Lower back pain: opioid use within 15 days of onset
associated with increased likelihood of receiving 5 or
more prescriptions from 30-730 days following onset
Versus no opioid use:
• 1 to 140 mg morphine equivalents: adjusted OR 2.08 (95% CI
1.55 to 2.78)
• >=450 mg morphine equivalents: adjusted OR 6.14 (95% CI
4.92 to 7.66)

22. CONTEXTUAL EVIDENCE REVIEW

23. Effectiveness of
nonpharmacologic therapy
• CBT
– Helps patients understand and modify factors and
processes that exacerbate pain
– Has been shown to have small, positive effects on
disability and catastrophizing, and an improvement in
symptoms
• Exercise
– Helps to restore the normal range of motion and
muscle conditioning
– Demonstrated effectiveness in improving pain and
function in CLBP and reduced pain in other conditions
such as OA and fibromyalgia
* Findings from systematic reviews

24. Effectiveness of
nonopioid pharmacologic therapy
• Acetaminophen and NSAIDs (e.g., first-line
pharmacotherapy for OA and low back pain)
– Potential harms: GI, renal, and cardiovascular risks
• Anticonvulsants and antidepressants (e.g.,
neuropathic pain)
– Pregabalin, gabapentin
– TCAs, SNRIs
• Useful in patients with concurrent pain and depression
• Limited comparative effectiveness data, but some
suggestion that opioids do not differ from non-
opioids in pain reduction
* Findings from systematic reviews

25. Benefits and harms: overdose risk

26. Benefits and harms:
Overdose risk
• Opioid-related overdose risk is dose-dependent
– 5 additional case control and cohort studies on the association
of opioid dosage and overdose risk excluded from clinical review
– Compared to doses < 20 MME, odds of overdose increased:
• 1.3 –1.9 at dosages of 20 to <50 MME
• 1.9 –4.6 at dosages of 50 to <100 MME
• 2.0 –8.9 at dosages of <= 100 MME
– Overdose risk significantly elevated >1830 MME total over 6
months
– 58-62% of fatal overdoses >50 MME
– 19% of controls (no overdose) prescribed daily doses >60 MME
vs. 48% fatal OD

27. Benefits and harms:
Factors that increase risk
• Pregnancy
• Older age
• Mental health disorder
• Substance use disorder
• Sleep-disordered breathing
• Note: Sensitivity and specificity of risk stratification
instruments are poor

28. Values and preferences:
Clinician perspective
• Lack confidence in their ability to prescribe opioids safely,
predict or detect prescription drug abuse, and discuss
abuse with their patients
• Feel pressured to treat with opioids
• Have difficulties interpreting patients' reports of pain
• Worry about secondary gain/diversion, and "abusive" or
"difficult" patients
• Feel frustrated, ungratified, and guilty when providing
chronic pain care

29. Values and preferences:
Patient perspective
• Many patients do not have an opinion about “opioids,” or
know what this term means
• One in three associate “narcotics” with addiction or
abuse
• Half fear “addiction” from long-term “narcotic” use
• Patients with chronic conditions:
– Ambivalent about risks and benefits
– Continue taking opioids even while recognizing them
to be ineffective in controlling pain

30. Resource allocation:
Costs and cost-effectiveness
• Direct medical costs: opioids vs pharmacologic vs non-
pharmacologic (OA; CLBP, 2012)
– Acetaminophen, NSAIDs, TCAs, and massage therapy
were associated with lower mean and median annual
costs relative to opioid therapy
– COX-2 inhibitors, SNRIs, anticonvulsants, topical
analgesics, PT, and CBT also associated with lower
median costs
• Cost-benefit for opioid therapy difficult to estimate due
to a lack of available evidence on benefits

31. RECOMMENDATIONS

32. Organization of Recommendations
12 recommendations grouped into three
conceptual areas:
• Determining when to initiate or continue opioids
for chronic pain
• Opioid selection, dosage, duration, follow-up,
and discontinuation
• Assessing risk and addressing harms of opioid use

33. DETERMINING WHEN TO INITIATE OR
CONTINUE OPIOIDS FOR CHRONIC PAIN

34. Recommendation 1
• Nonpharmacologic therapy and nonopioid
pharmacologic therapy are preferred for chronic
pain. Clinicians should consider opioid therapy
only if expected benefits for both pain and
function are anticipated to outweigh risks to the
patient. If opioids are used, they should be
combined with nonpharmacologic therapy and
nonopioid pharmacologic therapy, as
appropriate.
Recommendation category: A, Evidence type: 3

35. Opioids not first-line or routine
therapy for chronic pain
• Use nonpharmacologic therapy (e.g., exercise therapy,
CBT) to reduce pain and improve function
• Use nonopioid pharmacologic therapy (e.g., NSAIDS,
acetaminophen, anticonvulsants, SNRIs) when benefits
outweigh risks, combined with nonpharmacologic
therapy
• When opioids used, combine with nonpharmacologic
therapy and nonopioid pharmacologic therapy to
provide greater benefits

36. Recommendation 2
• Before starting opioid therapy for chronic pain,
clinicians should establish treatment goals with
all patients, including realistic goals for pain and
function, and should consider how therapy will
be discontinued if benefits do not outweigh risks.
Clinicians should continue opioid therapy only if
there is clinically meaningful improvement in pain
and function that outweighs risks to patient
safety.
Recommendation category: A, Evidence type: 4

37. Establish and measure progress
toward goals
• Before initiating opioid therapy for chronic pain,
– determine how effectiveness will be evaluated
– establish treatment goals with patients
• pain relief
• function
• Assess progress using 3-item PEG Assessment Scale*
– Pain average (0-10)
– interference with Enjoyment of life (0-10)
– interference with General activity (0-10)
*30% = clinically meaningful improvement

38. Recommendation 3
• Before starting and periodically during opioid
therapy, clinicians should discuss with patients
known risks and realistic benefits of opioid
therapy and patient and clinician responsibilities
for managing therapy.
Recommendation category: A, Evidence type: 3

39. Ensure patients are aware of potential
benefits, harms, and alternatives to opioids
• Be explicit and realistic about expected benefits
• Emphasize improvement in function as a primary goal
• Discuss
– serious and common adverse effects
– increased risks of overdose
• at higher dosages
• when opioids are taken with other drugs or alcohol
– periodic reassessment, PDMP and UDT checks
– risks to family members and individuals in the community

40. OPIOID SELECTION, DOSAGE,
DURATION, FOLLOW-UP, AND
DISCONTINUATION

41. Recommendation 4
• When starting opioid therapy for chronic pain,
clinicians should prescribe immediate-release
opioids instead of extended-release/long-acting
(ER/LA) opioids.
Recommendation category: A, Evidence type: 4

42. Choose predictable pharmacokinetics and
pharmacodynamics to minimize overdose risk
• In general, avoid the use of immediate-release opioids in
combination with ER/LA opioids
• Methadone should not be the first choice for an ER/LA
opioid; Only clinicians who are familiar with
methadone’s unique risk profile and who are prepared to
educate and closely monitor their patients should
consider prescribing it for pain
• Only consider prescribing transdermal fentanyl if familiar
with the dosing and absorption properties and prepared
to educate their patients about its use

43. Recommendation 5
• When opioids are started, clinicians should prescribe
the lowest effective dosage. Clinicians should use
caution when prescribing opioids at any dosage,
should carefully reassess evidence of individual
benefits and risks when increasing dosage to ≥50
morphine milligram equivalents (MME)/day, and
should avoid increasing dosage to ≥90 MME/day or
carefully justify a decision to titrate dosage to >90
MME/day.
Recommendation category: A, Evidence type: 3

44. Start low and go slow
• Start opioids at the lowest effective dosage
• Increase dosage by the smallest practical amount
• If total opioid dosage >50 MME/day
– reassess pain, function, and treatment
– increase frequency of follow-up
– consider offering naloxone
• Avoid increasing opioid dosages to >90 MME/day
• If escalating dosage requirements
– discuss other pain therapies with the patient
– consider working with the patient to taper opioids down or
off
– consider consulting a pain specialist

45. When patients are already receiving
high dosages
• Offer established patients already taking > 90
MME/day the opportunity to re-evaluate their
continued use of high opioid dosages in light of
recent evidence regarding the association of opioid
dosage and overdose risk
• For patients who agree to taper opioids to lower
dosages, collaborate with the patient on a tapering
plan (see Recommendation 7)

46. Recommendation 6
• Long-term opioid use often begins with
treatment of acute pain. When opioids are
used for acute pain, clinicians should prescribe
the lowest effective dose of immediate-
release opioids and should prescribe no
greater quantity than needed for the expected
duration of pain severe enough to require
opioids. Three days or less will often be
sufficient; more than seven days will rarely be
needed.
Recommendation category: A, Evidence type: 4

47. When opioids are needed for
acute pain
• Prescribe the lowest effective dose
• Prescribe amount to match the expected duration
of pain severe enough to require opioids
• Often <3 days and rarely more than 7 days needed
• Do not prescribe additional opioids “just in case”
• Re-evaluate patients with severe acute pain that
continues longer than expected to confirm or
revise the initial diagnosis and adjust management
• Do not prescribe ER/LA opioids for acute pain

48. Recommendation 7
• Clinicians should evaluate benefits and harms
with patients within 1 to 4 weeks of starting
opioid therapy for chronic pain or of dose
escalation. Clinicians should evaluate benefits
and harms of continued therapy with patients
every 3 months or more frequently. If benefits do
not outweigh harms of continued opioid therapy,
clinicians should optimize other therapies and
work with patients to taper opioids to lower
dosages or to taper and discontinue opioids.
Recommendation category: A, Evidence type: 4

49. Follow-up
Re-evaluate patients
• within 1 - 4 weeks of starting long-term therapy or of
dosage increase
• at least every 3 months or more frequently
At follow up, determine whether
• opioids continue to meet treatment goals
• there are common or serious adverse events or early
warning signs
• benefits of opioids continue to outweigh risks
• opioid dosage can be reduced or opioids can be
discontinued

50. Tapering opioids
• Offer to work with patients to taper opioids down or off when
– no sustained clinically meaningful improvement in pain and function
– opioid dosages >50 MME/day without evidence of benefit
– concurrent benzodiazepines that can’t be tapered off
– patients request dosage reduction or discontinuation
– patients experience overdose, other serious events, warning signs
• Taper slowly enough to minimize opioid withdrawal
– a decrease of 10% of per week is a reasonable starting point
• Access appropriate expertise for tapering during pregnancy
• Optimize nonopioid pain management, psychosocial support

51. ASSESSING RISK AND ADDRESSING
HARMS OF OPIOID USE

52. Recommendation 8
• Before starting and periodically during
continuation of opioid therapy, clinicians should
evaluate risk factors for opioid-related harms.
Clinicians should incorporate into the
management plan strategies to mitigate risk,
including considering offering naloxone when
factors that increase risk for opioid overdose, such
as history of overdose, history of substance use
disorder, higher opioid dosages (≥50 MME/day),
or concurrent benzodiazepine use, are present.
Recommendation category: A, Evidence type: 4

53. Risk factors increase susceptibility to
opioid-associated harms
• Avoid prescribing opioids to patients with moderate or
severe sleep-disordered breathing when possible
• Carefully weigh risks and benefits with pregnant patients
• Additional caution with renal or hepatic insufficiency, >65
• Ensure treatment for depression is optimized
• Consider offering naloxone when patients
– have a history of overdose
– have a history of substance use disorder
– are taking central nervous system depressants with opioids
– are on higher dosages of opioids (> 50 MME/day)

54. Recommendation 9
• Clinicians should review the patient’s history of
controlled substance prescriptions using state
prescription drug monitoring program (PDMP)
data to determine whether the patient is
receiving opioid dosages or dangerous
combinations that put him or her at high risk for
overdose. Clinicians should review PDMP data
when starting opioid therapy for chronic pain and
periodically during opioid therapy for chronic
pain, ranging from every prescription to every 3
months.
Recommendation category: A, Evidence type: 4

55. If prescriptions from multiple sources, high
dosages, or dangerous combinations
• Discuss safety concerns, increased risk of overdose with patient
• For patients receiving high total opioid dosages, consider tapering
to a safer dosage, consider offering naloxone
• Discuss safety concerns with others prescribing to your patient
• Consider opioid use disorder and discuss concerns with your patient
• If you suspect your patient might be sharing or selling opioids and
not taking them, consider urine drug testing to assist in determining
whether opioids can be discontinued without causing withdrawal
• Do not dismiss patients from care—use the opportunity to provide
potentially lifesaving information and interventions

56. Recommendation 10
• When prescribing opioids for chronic pain,
clinicians should use urine drug testing before
starting opioid therapy and consider urine drug
testing at least annually to assess for prescribed
medications as well as other controlled
prescription drugs and illicit drugs.
Recommendation category: B, Evidence type: 4

57. Use UDT to assess for prescribed opioids
and other drugs that increase risk
• Be familiar with drug testing panels and how to interpret results
• Do not test for drugs that would not affect patient management
• Before ordering urine drug testing
– explain to patients that testing is intended to improve their safety
– explain expected results
– ask patients whether there might be unexpected results
• Discuss unexpected results with local lab or toxicologist and
patients
• Verify unexpected, unexplained results using specific test
• Do not dismiss patients from care based on a urine drug test

58. Recommendation 11
• Clinicians should avoid prescribing opioid pain
medication and benzodiazepines concurrently
whenever possible.
Recommendation category: A, Evidence type: 3

59. Avoid concurrent opioids and
benzodiazepines whenever possible
• Taper benzodiazepines gradually
• Offer evidence-based psychotherapies for anxiety
– cognitive behavioral therapy
– specific anti-depressants approved for anxiety
– other non-benzodiazepine medications approved for
anxiety
• Coordinate care with mental health professionals

60. Recommendation 12
• Clinicians should offer or arrange evidence-based
treatment (usually medication-assisted treatment
with buprenorphine or methadone in
combination with behavioral therapies) for
patients with opioid use disorder.
Recommendation category: A, Evidence type: 2

61. If you suspect opioid use disorder
• Discuss with your patient, provide opportunity to disclose
concerns
• Assess for OUD using DSM-5 criteria. If present, offer or
arrange MAT
– buprenorphine through an office-based buprenorphine treatment
provider* or an opioid treatment program specialist**
– methadone maintenance therapy from an opioid treatment program
specialist**
– oral or long-acting injectable formulations of naltrexone (for highly
motivated non-pregnant adults)
Consider obtaining a waiver to prescribe buprenorphine for OUD
(see http://www.samhsa.gov/medication-assisted-treatment/buprenorphine-waiver-management)
*SAMHSA’s buprenorphine physician locator: http://buprenorphine.samhsa.gov/bwns_locator
**SAMHSA’s Opioid Treatment Program Directory: http://dpt2.samhsa.gov/treatment/directory.aspx

62. TRANSLATION AND
IMPLEMENTATION

63. Translation materials
• Website
• Checklist/algorithm
• Mobile application (including MME calculator)
• Fact sheets
– assessing benefit and harm
– MME conversions
– nonpharmacologic and nonopioid pharmacologic tx
options
– checking the prescription drug monitoring program
– use of opioid therapy in pregnant women
• Poster

65. Complementary activities for
consideration
• EHR clinical decision support and defaults
• Clinician education
• Insurance and pharmacy benefit manager mechanisms
• Clinical quality improvement measures and initiatives
• Policy initiatives to address barriers
– improving PDMP accessibility and interoperability
– improving access to medication-assisted treatment
– coverage for nonpharmacologic therapies and risk
mitigation strategies (e.g., urine drug testing)
• Research

66. Thank you
For more information see:
http://www.cdc.gov/drugoverdose/prescribing/guideline.html
The recommendations presented herein were in draft form upon submission of the
presentation and had not yet been formally disseminated by the Centers for
Disease Control and Prevention. At the time of submission, the content within the
presentation did not represent and should not be construed to represent any
agency determination or policy.

67. Development of the CDC
Opioid Prescribing Guidelines
for Chronic Pain in Primary Care
Presenters:
• Tamara Haegerich, PhD, Deputy Associate Director for
Science, Division of Unintentional Injury Prevention, CDC
• Deborah Dowell, MD, MPH, Senior Medical Advisor, Division
of Unintentional Injury Prevention, CDC
Clinical Track
Moderator: Mark D. Birdwhistell, MPA, Vice President
for Administration and External Affairs, University of
Kentucky HealthCare