Morbidity and Mortality Weekly Report
Recommendations and Reports / Vol. 71 / No. 3 November 4, 2022
CDC Clinical Practice Guideline for Prescribing
Opioids for Pain — United States, 2022
U.S. Department of Health and Human Services
Centers for Disease Control and Prevention
, Recommendations and Reports
CONTENTS CONTENTS (Continued)
Introduction.............................................................................................................1 Recommendation 6............................................................................................ 38
Clinical Practice Guideline Development Methods...................................9 Recommendation 7............................................................................................ 40
Recommendations.............................................................................................. 15 Assessing Risk and Addressing Potential Harms of Opioid Use......... 43
Determining Whether or Not to Recommendation 8............................................................................................ 43
Initiate Opioids for Pain.................................................................................. 17 Recommendation 9............................................................................................ 48
Recommendation 1 ........................................................................................... 17 Recommendation 10......................................................................................... 50
Recommendation 2 ........................................................................................... 21 Recommendation 11......................................................................................... 52
Selecting Opioids and Determining Recommendation 12......................................................................................... 54
Opioid Dosages................................................................................................. 28 Conclusion and Future Directions................................................................. 59
Recommendation 3............................................................................................ 28 References.............................................................................................................. 62
Recommendation 4............................................................................................ 30 Appendix: Primary Clinical Questions, Detailed Methods, and
Recommendation 5............................................................................................ 32 Findings for the Systematic and Contextual Evidence Reviews...... 77
Deciding Duration of Initial Opioid Prescription and Conducting References.............................................................................................................. 88
Follow-Up............................................................................................................ 38
The MMWR series of publications is published by the Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC),
U.S. Department of Health and Human Services, Atlanta, GA 30329-4027.
Suggested citation: [Author names; first three, then et al., if more than six.] [Title]. MMWR Recomm Rep 2022;71(No. RR-#):[inclusive page numbers].
Centers for Disease Control and Prevention
Rochelle P. Walensky, MD, MPH, Director
Debra Houry, MD, MPH, Acting Principal Deputy Director
Daniel B. Jernigan, MD, MPH, Deputy Director for Public Health Science and Surveillance
Rebecca Bunnell, PhD, MEd, Director, Office of Science
Jennifer Layden, MD, PhD, Deputy Director, Office of Science
Leslie Dauphin, PhD, Director, Center for Surveillance, Epidemiology, and Laboratory Services
MMWR Editorial and Production Staff (Serials)
Charlotte K. Kent, PhD, MPH, Editor in Chief Martha F. Boyd, Lead Visual Information Specialist Ian Branam, MA,
Christine G. Casey, MD, Editor Alexander J. Gottardy, Maureen A. Leahy, Acting Lead Health Communication Specialist
Mary Dott, MD, MPH, Online Editor Julia C. Martinroe, Stephen R. Spriggs,Tong Yang, Kiana Cohen, MPH, Symone Hairston, MPH,
Terisa F. Rutledge, Managing Editor Visual Information Specialists Leslie Hamlin, Lowery Johnson,
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MMWR Editorial Board
Timothy F. Jones, MD, Chairman
Matthew L. Boulton, MD, MPH David W. Fleming, MD Patricia Quinlisk, MD, MPH
Carolyn Brooks, ScD, MA William E. Halperin, MD, DrPH, MPH Patrick L. Remington, MD, MPH
Jay C. Butler, MD Jewel Mullen, MD, MPH, MPA Carlos Roig, MS, MA
Virginia A. Caine, MD Jeff Niederdeppe, PhD William Schaffner, MD
Jonathan E. Fielding, MD, MPH, MBA Celeste Philip, MD, MPH Morgan Bobb Swanson, BS
, CDC Clinical Practice Guideline for Prescribing Opioids for Pain —
United States, 2022
Deborah Dowell, MD1; Kathleen R. Ragan, MSPH1; Christopher M. Jones, PharmD, DrPH2; Grant T. Baldwin, PhD1; Roger Chou, MD3
1Division of Overdose Prevention, National Center for Injury Prevention and Control, CDC;
2Office of the Director, National Center for Injury Prevention and Control, CDC;
3Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon
Summary
This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients
aged ≥18 years. It updates the CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016 (MMWR
Recomm Rep 2016;65[No. RR-1]:1–49) and includes recommendations for managing acute (duration of <1 month), subacute
(duration of 1–3 months), and chronic (duration of >3 months) pain. The recommendations do not apply to pain related to
sickle cell disease or cancer or to patients receiving palliative or end-of-life care. The guideline addresses the following four areas:
1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding
duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid
use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
framework. Recommendations are based on systematic reviews of the scientific evidence and reflect considerations of benefits and
harms, patient and clinician values and preferences, and resource allocation. CDC obtained input from the Board of Scientific
Counselors of the National Center for Injury Prevention and Control (a federally chartered advisory committee), the public, and
peer reviewers. CDC recommends that persons with pain receive appropriate pain treatment, with careful consideration of the
benefits and risks of all treatment options in the context of the patient’s circumstances. Recommendations should not be applied
as inflexible standards of care across patient populations. This clinical practice guideline is intended to improve communication
between clinicians and patients about the benefits and risks of pain treatments, including opioid therapy; improve the effectiveness
and safety of pain treatment; mitigate pain; improve function and quality of life for patients with pain; and reduce risks associated
with opioid pain therapy, including opioid use disorder, overdose, and death.
Introduction experienced “high-impact” chronic pain, defined as having pain
on most days or every day during the past 3 months that limited
Background life or work activities (5). Pain, especially chronic pain, can
Pain is one of the most common reasons adults seek medical affect almost every aspect of a person’s life, leading to impaired
care in the United States (1). Acute pain, a nearly universal physical functioning, poor mental health, and reduced quality
experience, is a physiologic response to noxious stimuli that of life, and contributes to substantial morbidity each year (6).
can become pathologic. Acute pain is usually sudden in onset In 2011, the economic costs of chronic pain were estimated
and time limited (defined in this clinical practice guideline to range from $560 to $635 billion in annual direct medical
as having a duration of <1 month) and often is caused by costs, lost productivity, and disability (2).
injury, trauma, or medical treatments such as surgery (2,3). Pain is a complex phenomenon influenced by multiple
Unresolved acute pain or subacute pain (defined in this clinical factors, including biologic, psychological, and social factors
practice guideline as pain that has been present for 1–3 months) (7). This complexity means substantial heterogeneity exists
can evolve into chronic pain (4). Chronic pain typically lasts in the effectiveness of various pain treatments, depending
>3 months (4) and can be the result of an underlying medical on the type of underlying pain or condition being treated
disease or condition, injury, medical treatment, inflammation, (7–11). Patients might experience persistent pain that is
or unknown cause (2). Approximately one in five U.S. adults not well controlled (6). Chronic pain often co-occurs with
had chronic pain in 2019 and approximately one in 14 adults behavioral health conditions, including mental and substance
use disorders (12,13). Patients with chronic pain also are at
increased risk for suicidal ideation and behaviors (14,15).
Corresponding author: Division of Overdose Prevention, National Center Data from death investigations in 18 states during 2003–2014
for Injury Prevention and Control, CDC. Email: cdcinfo@cdc.gov.
indicate that approximately 9% of suicide decedents had
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / November 4, 2022 / Vol. 71 / No. 3 1
,evidence of having chronic pain at the time of death; however, evidence of misuse for Black patients compared with White
this is likely an underestimate because of the limitations of the patients (36). Differentially untreated or undertreated pain
underlying data sources used in the study (16). These factors as a result of clinician biases persists and demands immediate
and potentially harmful outcomes associated with chronic pain and sustained attention and action (37–40).
for some persons add to the clinical complexity and underscore Because of the clinical, psychological, and social consequences
the importance of adequately treating and providing care associated with pain, including limitations in activities, lost
to persons with pain. Thus, prevention, assessment, and work productivity, reduced quality of life, and pervasive stigma,
treatment of pain is a persistent challenge for clinicians. Pain it is essential that clinicians have the training, education,
might go unrecognized, and some persons (e.g., members of guidance, and resources to provide appropriate, holistic, and
marginalized racial and ethnic groups; women; older persons; compassionate care for patients with pain (2,6). An important
persons with cognitive impairment; persons with mental and aim of pain management is the provision of person-centered
substance use disorders, sickle cell disease, or cancer-related care built on trust between patients and clinicians. Such care
pain; and persons at the end of life) can be at risk for inadequate includes appropriate evaluation to identify potentially reversible
pain treatment (2,6,17–23). causes of pain and establish a diagnosis and measurable
Although substantial opportunity exists for improved pain treatment outcomes that focus on optimizing function and
management broadly across the United States, data underscore quality of life (6). To achieve this aim, it is important that
opportunities for addressing specific, long-standing health clinicians consider the full range of pharmacologic and
disparities (24–26) in the treatment of pain. For example, nonpharmacologic treatments for pain care, and that health
patients who identify as Black or African American (Black), systems, payers, and governmental programs and entities make
Hispanic or Latino (Hispanic), and Asian receive fewer the full spectrum of evidence-based treatments accessible to
postpartum pain assessments relative to White patients (27). patients with pain and their treating clinicians.
Black (28,29) and Hispanic (29) patients are less likely than The range of therapeutic options has historically been
White patients to receive analgesia for acute pain. Among inaccessible to many patients because of factors such as
Black and White patients receiving opioids for pain, Black inadequate clinician education, training, and guidance;
patients are less likely to be referred to a pain specialist, and unconscious bias; a shortage of pain management specialists;
Black patients receive prescription opioids at lower dosages insufficient access to treatment modalities such as behavioral
than White patients (24,30). Racial and ethnic differences therapy; siloed health systems; insurance coverage and
remain even after adjusting for access-related factors, the reimbursement policies; and lack of clarity about the evidence
needs and preferences of patients, and the appropriateness of supporting different pain treatments (6,17,41–46). Partly
the intervention (25). These disparities appear to be further because of these factors affecting access to a wide range of
magnified for Black and Hispanic patients who live in treatment modalities, for many years medications such as
socioeconomically disadvantaged neighborhoods (26). Women prescription opioids have been the mainstay to treat pain,
might be at higher risk for inadequate pain management despite very limited evidence to support their long-term
(31), although they have higher opioid prescription fill rates (>1 year) benefits; most placebo-controlled trials have been
(32) than men at a population level. Geographic disparities <6 weeks in duration (2,6,47,48).
contribute to increased use of opioids for conditions for which Opioids can be essential medications for the management
nonopioid treatment options might be preferred but are less of pain; however, they carry considerable potential risk.
available. For example, adults living in rural areas are more A systematic review published in 2014 by the Agency for
likely to be prescribed opioids for chronic nonmalignant Healthcare Research and Quality (AHRQ) found insufficient
pain than adults living in nonrural areas (33). Although not evidence to demonstrate long-term benefits of prescription
Hispanic or Latino (non-Hispanic) American Indian or Alaska opioid treatment for chronic pain, and long-term prescription
Native and non-Hispanic White populations have experienced opioid use was found to be associated with increased risk for
much higher rates of prescription opioid–related overdose overdose and opioid misuse, among other risks (47). Some
deaths than non-Hispanic Black, Hispanic, or non-Hispanic risks, such as overdose, were dose dependent (47). In 2014, on
Asian or Pacific Islander populations (34), application of the basis of accumulating evidence of potential risks to patients,
safeguards in opioid prescribing are disproportionately applied the Food and Drug Administration (FDA) required new safety
to Black patients. In one study, Black patients were more likely labeling changes for extended-release and long-acting opioids.
than White patients to receive regular office visits and have Changes included a boxed warning on the “risks of addiction,
restricted early refills (35). In another study, clinicians were abuse, and misuse, which can lead to overdose and death”
substantially more likely to discontinue opioids if there was and, for patients receiving opioids during pregnancy, the risk
2 MMWR / November 4, 2022 / Vol. 71 / No. 3 US Department of Health and Human Services/Centers for Disease Control and Prevention
,for neonatal abstinence syndrome (a group of conditions that education and training, partnerships with health systems and
can occur when newborns withdraw from certain substances payers, and multiple clinical tools and fact sheets (57).
including opioids; withdrawal caused by in utero exposure to The number of overall opioid prescriptions in the United
opioids also is called neonatal opioid withdrawal syndrome) States declined after 2012, and further declines have been
(49). In 2016, these warnings were added to the labels for observed after the release of the 2016 CDC Opioid Prescribing
immediate-release opioids (50). Guideline (58). The timing of this release was associated
In addition to the potential risks to patients, prescribed with accelerated decreases in overall opioid prescribing and
opioids have the potential for diversion and nonmedical declines in potentially high-risk prescribing (e.g., high-dosage
use among persons to whom they were not prescribed (51). opioid prescribing and concurrent prescribing of opioid
In the United States, opioid prescribing increased fourfold pain medication and benzodiazepines) (58,59). The release
during 1999–2010; this increase was paralleled by an of the 2016 CDC Opioid Prescribing Guideline also was
approximately fourfold increase in overdose deaths involving temporally associated with modest increases in the prescribing
prescription opioids during the same period (52) and increases of nonopioid pain medication (60). Although not the intent
in prescription opioid use disorder (53). In addition to the of the 2016 CDC Opioid Prescribing Guideline, design and
increased overall volume of opioid prescriptions during this implementation of new laws, regulations, and policies also
period, how opioids were prescribed also changed; opioids appeared to reflect its recommendations. For example, since
increasingly were prescribed at higher dosages and for longer 2016, consistent with SUPPORT Act requirements (61), some
durations, prescribing behaviors associated with opioid use state Medicaid programs have used the guideline and other
disorder and overdose (54,55). The limited evidence of long- resources to promote nonopioid options for chronic pain
term effectiveness of opioids for chronic pain, coupled with management (62). Approximately half of all states have passed
risks to patients and to persons using prescription opioids that legislation limiting initial opioid prescriptions for acute pain
were not prescribed to them, underscored the importance of to a ≤7-day supply (63), and many insurers, pharmacy benefit
reducing inappropriate opioid prescribing while advancing managers, and pharmacies have enacted similar policies (64).
evidence-based pain care to improve the lives of persons living At least 17 states have passed laws requiring or recommending
with pain. the coprescription of naloxone in the presence of overdose risk
CDC recognized the need for a national guideline on pain factors, such as high dosages of opioids or concomitant opioid
management that could improve appropriate opioid prescribing pain medications and benzodiazepines (65).
while minimizing opioid-related risks and released the CDC Although some laws, regulations, and policies that appear
Guideline for Prescribing Opioids for Chronic Pain — United to support recommendations in the 2016 CDC Opioid
States, 2016 (referred to as the 2016 CDC Opioid Prescribing Prescribing Guideline might have had positive results for
Guideline hereafter). The 2016 CDC Opioid Prescribing some patients, they are inconsistent with a central tenet of
Guideline included 12 recommendations for the prescribing the guideline: that the recommendations are voluntary and
of opioids for chronic pain by primary care clinicians in intended to be flexible to support, not supplant, individualized,
outpatient settings, excluding active cancer treatment, palliative patient-centered care. Of particular concern, some policies
care, and end-of-life care (56). The recommendations in the purportedly drawn from the 2016 CDC Opioid Prescribing
2016 CDC Opioid Prescribing Guideline were based on a Guideline have been notably inconsistent with it and have
systematic review of the best-available evidence at the time, gone well beyond its clinical recommendations (6,66,67). Such
along with input from experts and the public and review and misapplication includes extension to patient populations not
deliberation by the Board of Scientific Counselors (BSC) covered in the 2016 CDC Opioid Prescribing Guideline (e.g.,
of the National Center for Injury Prevention and Control cancer and palliative care patients), rapid opioid tapers and
(NCIPC) (a federally chartered advisory committee). The abrupt discontinuation without collaboration with patients,
goals of the guideline were to 1) ensure that clinicians and rigid application of opioid dosage thresholds, application of
patients considered safer and more effective pain treatment; the guideline’s recommendations for opioid use for pain to
2) improve patient outcomes, such as reduced pain and medications for opioid use disorder treatment (previously
improved function; and 3) reduce the number of persons referred to as medication assisted treatment), duration
who developed opioid use disorder, experienced overdose, limits by insurers and pharmacies, and patient dismissal and
or experienced other prescription opioid–related adverse abandonment (66–68). These actions are not consistent
events (56). To facilitate uptake and implementation of the with the 2016 CDC Opioid Prescribing Guideline and
2016 CDC Opioid Prescribing Guideline in clinical practice, have contributed to patient harm, including untreated and
CDC used a broad-reaching strategy that included clinician undertreated pain, serious withdrawal symptoms, worsening
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / November 4, 2022 / Vol. 71 / No. 3 3
,pain outcomes, psychological distress, overdose, and suicidal This clinical practice guideline expands and updates
ideation and behavior (66–71). the 2016 CDC Opioid Prescribing Guideline to provide
evidence-based recommendations for prescribing opioid
Rationale pain medication for acute, subacute, and chronic pain for
outpatients aged ≥18 years, excluding pain management
Since release of the 2016 CDC Opioid Prescribing related to sickle cell disease, cancer-related pain treatment,
Guideline, new evidence has emerged on the benefits and palliative care, and end-of-life care (Boxes 1 and 2). Lessons
risks of prescription opioids for both acute and chronic learned from the development of the 2016 CDC Opioid
pain, comparisons with nonopioid pain treatments, dosing Prescribing Guideline informed the process used to generate
strategies, opioid dose-dependent effects, risk mitigation this update. This update leverages new data to expand content
strategies, and opioid tapering and discontinuation (7–11). on prescription opioids for acute and subacute pain throughout
This evidence includes studies on misapplication of the 2016 the recommendations. Importantly, the update also aims to
CDC Opioid Prescribing Guideline (66), benefits and risks clearly delineate recommendations that apply to patients who
of different tapering strategies and rapid tapering associated are being considered for initial treatment with prescription
with patient harm (68,71–73), challenges in patient access to opioids and patients who have been receiving opioids as part
opioids (6), patient abandonment and abrupt discontinuation of their ongoing pain management.
of opioids (71), a seminal randomized clinical trial comparing CDC developed a draft clinical practice guideline on
prescription opioids to nonopioid medications on long-term the basis of five systematic reviews of the best-available
pain outcomes (74), the association of characteristics of initial evidence on the benefits and risks of prescription opioids,
opioid prescriptions with subsequent likelihood for long-term nonopioid pharmacologic treatments, and nonpharmacologic
opioid use (75,76), and the small proportion of opioids used treatments. The draft clinical practice guideline was reviewed
by patients compared with the amount prescribed to them for by an independent federal advisory committee (the Board
postoperative pain (77–79). of Scientific Counselors of the National Center for Injury
Opioid medications remain a common treatment for pain Prevention and Control), peer reviewers, and the public and
despite declines in the number of opioid prescriptions after was revised after feedback from these reviews. Additional
2012 (58). During 2015–2018, approximately 6% of U.S. insights from patients, caregivers, and clinicians shared during
adults reported use of one or more prescription opioids during virtual conversations held in 2020 were incorporated in the
the past 30 days (80), and in 2020, approximately 143 million update. Importantly, to discourage the misapplication of opioid
opioid prescriptions were dispensed from pharmacies in the pain medication dosage thresholds as inflexible standards,
United States (81). Rates of opioid prescribing continue to vary revised recommendation statement language emphasizes
across states, medical specialties, patient demographics, and pain principles such as avoiding increasing dosage above levels
conditions in ways that cannot be explained by the underlying likely to yield diminishing returns in benefits relative to risks
health status of the population, and often are discordant with to patients. More-specific considerations related to dosage
the 2016 CDC Opioid Prescribing Guideline recommendations have been moved to implementation considerations that
(25,77,82–84). The prevalence of prescription opioid misuse follow each recommendation statement, where more nuance is
and prescription opioid use disorder also has declined in recent offered to inform clinical decision-making and individualized
years. In 2019, among persons aged ≥12 years in the United patient care.
States, 9.7 million reported misuse of prescription opioids This clinical practice guideline provides recommendations
during the past year (a decrease from 12.5 million in 2015), and but does not replace clinical judgment and individualized,
1.4 million met criteria for a past-year prescription opioid use patient-centered decision-making. The recommendations are
disorder (a decrease from 2.0 million in 2015) (85). However, based on emerging evidence, including observational studies or
in 2020, prescription opioids remained the most commonly randomized clinical trials with notable limitations; thus, they
misused prescription drug in the United States (51). Also in should be considered in the context of the clinician-patient
2020, among those reporting misuse during the past year, 64.6% relationship built on shared understanding and a whole-person
reported the main reason for their most recent misuse was to approach that considers such factors as the patient’s physical
“relieve physical pain” compared with 11.3% to “feel good or get and psychological functioning, support needs, expected
high” and 2.3% “because I am hooked or have to have it” (51). health outcomes and well-being, home environment, and
Taken together, these factors underscore the need for an updated home and work responsibilities. Flexibility for clinicians and
clinical practice guideline on appropriate opioid prescribing for patients is paramount when making patient-centered clinical
pain and pain management. treatment decisions. The recommendations aim to improve
4 MMWR / November 4, 2022 / Vol. 71 / No. 3 US Department of Health and Human Services/Centers for Disease Control and Prevention
,BOX 1. Executive summary of the CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022
This clinical practice guideline updates and expands public comment opportunities available via Federal Register
the CDC Guideline for Prescribing Opioids for Chronic notices. CDC also sought input from the Board of Scientific
Pain — United States, 2016 (MMWR Recomm Rep Counselors of the National Center for Injury Prevention
2016;65[No. RR-1]:1–49]) and provides evidence-based and Control (BSC/NCIPC) (a federally chartered advisory
recommendations for primary care and other clinicians committee), federal partners, and peer reviewers with
(including physicians, nurse practitioners and other scientific and clinical expertise.
advanced practice registered nurses, physician assistants, The clinical evidence reviews found that a number of
and oral health practitioners) providing pain care, including nonpharmacologic treatments and a number of nonopioid
those prescribing opioids, for outpatients aged ≥18 years medications are associated with improvements in pain,
with acute (duration of <1 month) pain, subacute (duration function, or both, that appear comparable to improvements
of 1–3 months) pain, or chronic (duration of >3 months) associated with opioid use. Multiple noninvasive
pain. Recommendations on use of opioids for acute pain nonpharmacologic interventions (e.g., exercise and
and on tapering opioids for patients already receiving psychological therapies) are associated with improvements
opioid therapy have been substantially expanded in this in pain, function, or both, that are sustained after treatment
update. These recommendations do not apply to patients and are not associated with serious harms. Nonopioid drugs,
experiencing pain associated with the following conditions including serotonin and norepinephrine reuptake inhibitor
or settings: pain management related to sickle cell disease, (SNRI) antidepressants, pregabalin and gabapentin, and
cancer-related pain treatment, palliative care, and end-of-life nonsteroidal anti-inflammatory drugs (NSAIDs), are
care. Applicable outpatient settings include clinician offices, associated with small to moderate improvements in chronic
clinics, and urgent care centers. The recommendations do pain and function for certain chronic pain conditions.
not apply to providing care to patients who are hospitalized Nonopioid drug class–specific adverse events include serious
or in an emergency department or other observational cardiovascular, gastrointestinal, or renal effects with NSAIDs
setting from which they might be admitted to inpatient care. and sedation with anticonvulsants. Opioid therapy is
These recommendations do apply to prescribing for pain associated with similar or decreased effectiveness for pain and
management when patients are discharged from hospitals, function versus NSAIDs across several acute pain conditions
emergency departments, or other facilities. and with small improvements in short-term (1 to <6 months)
This clinical practice guideline addresses the following areas: pain and function compared with placebo; evidence was
1. Determining whether or not to initiate opioids found of attenuated pain reduction over time with opioids
for pain (between 3 and 6 months versus between 1 and 3 months).
2. Selecting opioids and determining opioid dosages Opioid therapy is associated with increased risk for serious
3. Deciding duration of initial opioid prescription and harms (including opioid use disorder and overdose) that
conducting follow-up appears to increase with increase in opioid dosage, without
4. Assessing risk and addressing potential harms of a clear threshold below which there is no risk. No validated,
opioid use reliable way exists to predict which patients will suffer serious
CDC developed this clinical practice guideline using the harm from opioid therapy. Evidence was sparse for long-
Grading of Recommendations Assessment, Development, term improvement of pain or function for any treatment
and Evaluation (GRADE) framework, and recommendations for chronic pain. Some evidence indicated that beneficial
are made based on a systematic review of the available effects of some nonpharmacologic therapies persist for
scientific evidence while considering benefits and harms; up to 12 months after the end of a course of a treatment.
values and preferences of patients, caregivers, and clinicians; Among 154 trials of nonopioid medications rated as good
and resource allocation (e.g., costs to patients or health or fair quality, eight were long term (≥1 year). A single
systems, including clinician time). CDC obtained input trial evaluated outcomes at 1 year for opioid medications
on this clinical practice guideline through individual (compared with nonopioid medications).
conversations with patients, caregivers, and clinicians and
Continued on the next page.
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / November 4, 2022 / Vol. 71 / No. 3 5
,BOX 1. (Continued) Executive summary of the CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022
CDC invited input on the draft clinical practice guideline increasing, continuing, or reducing opioid dosage. Before
and received approximately 5,500 public comments. Many of starting and periodically during continuation of opioid
these comments were related to experiences with pain or with therapy, clinicians should evaluate risk for opioid-related
the aftermath of a family member’s, friend’s, or significant harms and should work with patients to incorporate relevant
person’s overdose; barriers to and access to pain care and strategies to mitigate risk, including offering naloxone and
evidence-based treatment; concerns about the level of reviewing potential interactions with any other prescribed
specificity of recommendations; and overall communication medications or substances used. Clinicians should offer or
and implementation of the clinical practice guideline. Some arrange treatment with evidence-based medications to treat
respondents expressed concerns that insufficient specificity of patients with opioid use disorder.
recommendations might leave clinicians without sufficient CDC recommends that persons with pain receive
practical advice or context, whereas others were concerned appropriate pain treatment with careful consideration of the
that inclusion of more-specific recommendations or benefits and risks of all treatment options in the context of the
information in the guideline could facilitate misapplication patient’s circumstances. Clinicians should collaborate with
through adaption of the clinical practice guideline or patients when making treatment decisions and designing a
components of the guideline into rigid policies and laws. treatment plan, including when initiating or changing pain
CDC incorporated insights from public comments into the management strategies and particularly when considering
clinical practice guideline, including special considerations initiating, increasing, tapering, or discontinuing opioids.
for each recommendation. To help prevent misapplication Clinicians should avoid abrupt discontinuation of opioids,
of recommendations as inflexible rules and enable clinicians especially for patients receiving high dosages of opioids,
to account for individualized, person-centered clinical should avoid dismissing patients from care, and should
considerations, specific prescription dosages and durations ensure (provide or arrange) appropriate care for patients
are generally not included in the summary recommendation with pain and patients with complications from opioid use
statements, which highlight general principles. Greater (e.g., opioid use disorder). Quality and equitable care across
specificity is provided in implementation considerations and sociodemographic groups requires attention to mitigation
supporting rationales, which can offer more flexibility to help of potential barriers to care, such as through linguistically
clinicians weigh benefits and risks of different therapeutic tailored care and cost-assistance programs to ensure access
courses for specific patients. to appropriate pharmacotherapy, psychological support, and
Recommendation statements emphasize that opioids physical therapy as needed.
should be used only when benefits for pain and function This voluntary clinical practice guideline provides
are expected to outweigh risks. Before initiating opioid recommendations only and is intended to support, not
therapy for patients with pain, clinicians should discuss supplant, clinical judgment and individualized, person-
with patients the realistic benefits and known risks of opioid centered decision-making. This clinical practice guideline
therapy. Before starting ongoing opioid therapy for patients should not be applied as inflexible standards of care across
with subacute or chronic pain, clinicians should work with patient populations by health care professionals; health
patients to establish treatment goals for pain and function systems; pharmacies; third-party payers; or state, local,
and consider how opioid therapy will be discontinued if or federal organizations or entities. This clinical practice
benefits do not outweigh risks. When opioids are initiated, guideline is intended to improve communication between
clinicians should prescribe the lowest effective dosage of clinicians and patients about the benefits and risks of pain
immediate-release opioids for no longer than needed for the treatment, including opioid therapy for pain; improve the
expected duration of pain severe enough to require opioids. safety and effectiveness of pain treatment; mitigate pain;
During ongoing opioid therapy, clinicians should collaborate improve function and quality of life for patients with
with patients to evaluate and carefully weigh benefits and pain; and reduce risks associated with opioid pain therapy,
risks of continuing opioid therapy and exercise care when including opioid use disorder, overdose, and death.
6 MMWR / November 4, 2022 / Vol. 71 / No. 3 US Department of Health and Human Services/Centers for Disease Control and Prevention
,BOX 2. Intended use of CDC’s Clinical Practice Guideline for
Prescribing Opioids for Pain — United States, 2022
Scope and Audience
This clinical practice guideline is intended for clinicians who
This clinical practice guideline is are treating outpatients aged ≥18 years with acute (duration
• a clinical tool to improve communication between of <1 month), subacute (duration of 1–3 months), or chronic
clinicians and patients and empower them to make (duration of >3 months) pain, and excludes pain management
informed, person-centered decisions related to pain related to sickle cell disease, cancer-related pain treatment,
care together; palliative care, and end-of-life care. The recommendations are
• intended for primary care clinicians and other most relevant to clinicians whose scope of practice includes
clinicians providing pain care for outpatients aged prescribing opioids (e.g., physicians, nurse practitioners and
≥18 years with other advanced-practice registered nurses, physician assistants,
ï acute pain (duration of <1 month), and oral health practitioners). Because clinicians might work
ï subacute pain (duration of 1–3 months), or within team-based care, this clinical practice guideline also refers
ï chronic pain (duration of >3 months); and to and promotes integrated pain management and collaborative
• intended to be flexible to enable person-centered working relationships among clinicians (e.g., behavioral
decision-making, taking into account a patient’s health specialists such as social workers or psychologists,
expected health outcomes and well-being. pharmacists, and registered nurses). This guideline update
This clinical practice guideline is not includes recommendations for primary care clinicians (e.g.,
• a replacement for clinical judgment or individualized, internists and family physicians) and other clinicians managing
person-centered care; pain in outpatient settings (e.g., surgeons, emergency medicine
• intended to be applied as inflexible standards of care clinicians, occupational medicine clinicians, physical medicine
across patients or patient populations by health care and rehabilitation clinicians, and neurologists). Applicable
professionals, health systems, pharmacies, third-party settings include clinician offices, clinics, and urgent care
payers, or governmental jurisdictions or to lead to the centers. The recommendations do not apply to care provided
rapid tapering or abrupt discontinuation of opioids to patients who are hospitalized or in an emergency department
for patients; or other observational setting from which they might be
• a law, regulation, or policy that dictates clinical admitted to inpatient care. These recommendations do apply
practice or as a substitute for Food and Drug to prescribing for pain management for patients when they
Administration–approved labeling; are discharged from hospitals, emergency departments, or
• applicable to other facilities.
ï management of pain related to sickle cell disease, In addition to updating recommendations on the basis of new
ï management of cancer-related pain, or evidence regarding management of chronic pain, this clinical
ï palliative care or end-of-life care; or practice guideline is intended to assist clinicians in weighing
• focused on opioids prescribed for opioid use disorder. benefits and risks of prescribing opioid pain medication for
painful acute conditions (e.g., low back pain, neck pain, other
musculoskeletal pain, neuropathic pain, dental pain, kidney
communication between clinicians and patients about the stone pain, and acute episodic migraine) and pain related to
benefits and risks of prescription opioids and other pain procedures (e.g., postoperative pain and pain from oral surgery).
treatment strategies; improve the safety and effectiveness of In 2020, several of these indications were prioritized by an ad hoc
pain treatment; improve pain, function, and quality of life for committee of the National Academies of Sciences, Engineering,
persons with pain; and reduce the risks associated with opioid and Medicine (86) as those for which evidence-based clinical
pain treatment (including opioid use disorder, overdose, and practice guidelines would help inform prescribing practices, with
death) and with other pain treatment. the greatest potential effect on public health. This update includes
This clinical practice guideline provides voluntary clinical content on management of subacute painful conditions, when
practice recommendations for clinicians that should not be duration falls between that typically considered acute (defined as
used as inflexible standards of care. The recommendations are lasting <1 month) and chronic (defined as lasting >3 months).
not intended to be implemented as absolute limits for policy The durations used to define acute, subacute, and chronic pain
or practice across populations by organizations, health care might imply more specificity than is found in real-life patient
systems, or government entities. experience, when pain often gradually transitions from acute
to chronic. These time-bound definitions are not meant to be
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / November 4, 2022 / Vol. 71 / No. 3 7
, absolute but rather to be approximate guides to facilitate the for pain management in these contexts. Other guidelines
consideration and practical use of the recommendations by more specifically address pain management in these situations
clinicians and patients. (87,89–93); therefore, this clinical practice guideline does
The 2016 CDC Opioid Prescribing Guideline focused on not apply to patients experiencing pain associated with these
recommendations for primary care physicians. This clinical conditions or types of care. This does not imply that any other
practice guideline expands the scope to additional clinicians. types of pain are more or less worthy of effective treatment,
Although primary care physicians prescribe approximately only that clinicians are referred to existing clinical guidelines
37% of all opioid prescriptions, other clinicians, including that more specifically address unique considerations for
pain medicine clinicians (8.9%) and dentists (8.6%), account management of pain related to sickle cell disease, cancer-related
for considerable proportions of prescriptions. Pain medicine pain treatment, palliative care, and end-of-life care.
and physical medicine and rehabilitation clinicians prescribe This clinical practice guideline follows the Institute of
opioids at the highest rates, followed by orthopedic and Medicine’s definition of palliative care as care that provides
family medicine clinicians (83). Thus, expanding the scope relief from pain and other symptoms, supports quality of life,
to outpatient opioid prescribing can provide evidence-based and is focused on patients with serious advanced illness (94).
advice for many additional clinicians, including dentists and Palliative care can begin early in the course of treatment for any
other oral health providers, clinicians managing postoperative serious illness that requires advanced management of pain or
pain in outpatients, and clinicians providing pain management other distressing symptoms (94). In this guideline, end-of-life
for patients being discharged from emergency departments. care refers to care for persons in hospice care and others with a
Many principles of pain management are similar whether terminal illness or at high risk for dying in the near future in
or not the treating clinician is a pain management specialist, hospitals, receiving long-term services and supports (including
and many of the recommendations might be relevant for pain institutional care and home- and community-based services),
management specialists. Many pain management specialists or at home. This clinical practice guideline does not apply to
already follow principles outlined in this clinical practice patients undergoing cancer-related pain treatment, palliative
guideline; however, use by pain management specialists is not care, or end-of-life care because of the unique therapeutic goals,
the focus of this clinical practice guideline. Pain management ethical considerations, opportunities for medical supervision,
specialists often have extensive training and expertise in pain and balance of benefits and risks with opioid therapy in such
management modalities that other clinicians do not, and care. For example, for many persons at the end of life, serious
they might treat patients with clinical situations that are potential long-term opioid-related harms such as opioid use
more complex, less prevalent, and not well addressed by the disorder might not be relevant.
available evidence; therefore, the balance of benefits and risks Recommendations on pain management for patients with
to patients might differ when the treating clinician is a pain cancer and patients who have survived cancer are available
management specialist. in the National Comprehensive Cancer Network (NCCN)
The recommendations address the use of opioid pain Clinical Practice Guidelines in Oncology: Adult Cancer
medication in certain special populations (e.g., older adults Pain (90), NCCN Clinical Practice Guidelines in Oncology:
and pregnant persons) and in populations with conditions Survivorship (91), and Management of Chronic Pain in
posing special risks (e.g., a history of a substance use disorder). Survivors of Adult Cancers: American Society of Clinical
The recommendations do not address the use of opioid pain Oncology (ASCO) Clinical Practice Guideline (92). Because
medication in children or adolescents aged <18 years. The of unique considerations in management of pain related to
available evidence concerning the benefits and risks of long- sickle cell disease, which can change the balance of benefits
term opioid therapy in children and adolescents remains and risks of the use of opioids, clinicians should refer to the
limited, and few opioid medications provide information in American Society of Hematology (ASH) 2020 Guidelines for
their labeling regarding safety and effectiveness in pediatric Sickle Cell Disease: Management of Acute and Chronic Pain
patients. Guidelines and recommendations are available for (87). In 2018, NCCN and ASCO convened and led a meeting
pain management in children with sickle cell disease (87), for including representatives and guideline authors from NCNN,
children undergoing surgical procedures (88), and for palliative ASCO, ASH, and CDC to review existing pain management
care in adolescent and young adult patients with cancer (89). guidelines and guidelines then in development from these
Although some principles in this clinical practice guideline organizations (56,87,90–92). Meeting participants noted
might be helpful in the management of pain related to sickle that these guidelines applied to different patient populations
cell disease, cancer-related pain treatment, palliative care, and and target audiences but found no disagreement among
end-of-life care, some recommendations might not be relevant
8 MMWR / November 4, 2022 / Vol. 71 / No. 3 US Department of Health and Human Services/Centers for Disease Control and Prevention
