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  and includes recommendations for managing acute (duration of <1 month), subacute (duration of 1–3months), 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 , 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. Pain is one of the most common reasons adults seek medical care in the United States  found insufficient evidence to demonstrate long-term benefits of prescription opioid treatment for chronic pain, and long-term prescription opioid use was found to be associated with increased risk for overdose and opioid misuse, among other risks . The 2016 CDC Opioid Prescribing Guideline included 12 recommendations for the prescribing of opioids for chronic pain by primary care clinicians in outpatient settings, excluding active cancer treatment, palliative care, and end-of-life care  and provides evidence-based recommendations for primary care and other clinicians  providing pain care, including those prescribing opioids, for outpatients aged ≥18 years with acute (duration of <1 month) pain, subacute (duration of 1–3 months) pain, or chronic (duration of >3 months) pain. Recommendations on use of opioids for acute pain and on tapering opioids for patients already receiving opioid therapy have been substantially expanded in this update. These recommendations do not apply to patients experiencing pain associated with the following conditions or settings: pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care. Applicable outpatient settings include clinician offices, clinics, and urgent care centers. The recommendations do not apply to providing care to patients who are hospitalized or in an emergency department or other observational setting from which they might be admitted to inpatient care. These recommendations do apply to prescribing for pain management when patients are discharged from hospitals, emergency departments, or other facilities.This clinical practice guideline updates and expands the This clinical practice guideline addresses the following areas:Determining whether or not to initiate opioids for painSelecting opioids and determining opioid dosagesDeciding duration of initial opioid prescription and conducting follow-upAssessing risk and addressing potential harms of opioid useFederal Register notices. CDC also sought input from the Board of Scientific Counselors of the National Center for Injury Prevention and Control (BSC/NCIPC) , federal partners, and peer reviewers with scientific and clinical expertise.CDC developed this clinical practice guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made based on a systematic review of the available scientific evidence while considering benefits and harms; values and preferences of patients, caregivers, and clinicians; and resource allocation . CDC obtained input on this clinical practice guideline through individual conversations with patients, caregivers, and clinicians and public comment opportunities available via The clinical evidence reviews found that a number of nonpharmacologic treatments and a number of nonopioid medications are associated with improvements in pain, function, or both, that appear comparable to improvements associated with opioid use. Multiple noninvasive nonpharmacologic interventions  are associated with improvements in pain, function, or both, that are sustained after treatment and are not associated with serious harms. Nonopioid drugs, including serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants, pregabalin and gabapentin, and nonsteroidal anti-inflammatory drugs (NSAIDs), are associated with small to moderate improvements in chronic pain and function for certain chronic pain conditions. Nonopioid drug class–specific adverse events include serious cardiovascular, gastrointestinal, or renal effects with NSAIDs and sedation with anticonvulsants. Opioid therapy is associated with similar or decreased effectiveness for pain and function versus NSAIDs across several acute pain conditions and with small improvements in short-term (1 to <6 months) pain and function compared with placebo; evidence was found of attenuated pain reduction over time with opioids (between 3 and 6 months versus between 1 and 3 months). Opioid therapy is associated with increased risk for serious harms (including opioid use disorder and overdose) that appears to increase with increase in opioid dosage, without a clear threshold below which there is no risk. No validated, reliable way exists to predict which patients will suffer serious harm from opioid therapy. Evidence was sparse for long-term improvement of pain or function for any treatment for chronic pain. Some evidence indicated that beneficial effects of some nonpharmacologic therapies persist for up to 12 months after the end of a course of a treatment. Among 154 trials of nonopioid medications rated as good or fair quality, eight were long term (≥1 year). A single trial evaluated outcomes at 1 year for opioid medications (compared with nonopioid medications).CDC invited input on the draft clinical practice guideline and received approximately 5,500 public comments. Many of these comments were related to experiences with pain or with the aftermath of a family member’s, friend’s, or significant person’s overdose; barriers to and access to pain care and evidence-based treatment; concerns about the level of specificity of recommendations; and overall communication and implementation of the clinical practice guideline. Some respondents expressed concerns that insufficient specificity of recommendations might leave clinicians without sufficient practical advice or context, whereas others were concerned that inclusion of more-specific recommendations or information in the guideline could facilitate misapplication through adaption of the clinical practice guideline or components of the guideline into rigid policies and laws. CDC incorporated insights from public comments into the clinical practice guideline, including special considerations for each recommendation. To help prevent misapplication of recommendations as inflexible rules and enable clinicians to account for individualized, person-centered clinical considerations, specific prescription dosages and durations are generally not included in the summary recommendation statements, which highlight general principles. Greater specificity is provided in implementation considerations and supporting rationales, which can offer more flexibility to help clinicians weigh benefits and risks of different therapeutic courses for specific patients.Recommendation statements emphasize that opioids should be used only when benefits for pain and function are expected to outweigh risks. Before initiating opioid therapy for patients with pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy. Before starting ongoing opioid therapy for patients with subacute or chronic pain, clinicians should work with patients to establish treatment goals for pain and function and consider how opioid therapy will be discontinued if benefits do not outweigh risks. When opioids are initiated, clinicians should prescribe the lowest effective dosage of immediate-release opioids for no longer than needed for the expected duration of pain severe enough to require opioids. During ongoing opioid therapy, clinicians should collaborate with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy and exercise care when increasing, continuing, or reducing opioid dosage. Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substances used. Clinicians should offer or arrange treatment with evidence-based medications to treat patients with opioid use disorder.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. Clinicians should collaborate with patients when making treatment decisions and designing a treatment plan, including when initiating or changing pain management strategies and particularly when considering initiating, increasing, tapering, or discontinuing opioids. Clinicians should avoid abrupt discontinuation of opioids, especially for patients receiving high dosages of opioids, should avoid dismissing patients from care, and should ensure (provide or arrange) appropriate care for patients with pain and patients with complications from opioid use . Quality and equitable care across sociodemographic groups requires attention to mitigation of potential barriers to care, such as through linguistically tailored care and cost-assistance programs to ensure access to appropriate pharmacotherapy, psychological support, and physical therapy as needed.This voluntary clinical practice guideline provides recommendations only and is intended to support, not supplant, clinical judgment and individualized, person-centered decision-making. This clinical practice guideline should not be applied as inflexible standards of care across patient populations by health care professionals; health systems; pharmacies; third-party payers; or state, local, or federal organizations or entities. This clinical practice guideline is intended to improve communication between clinicians and patients about the benefits and risks of pain treatment, including opioid therapy for pain; improve the safety and effectiveness 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.BOX 2This clinical practice guideline isa clinical tool to improve communication between clinicians and patients and empower them to make informed, person-centered decisions related to pain care together;intended for primary care clinicians and other clinicians providing pain care for outpatients aged ≥18 years withacute pain (duration of <1 month),subacute pain (duration of 1–3 months), orchronic pain (duration of >3 months); andintended to be flexible to enable person-centered decision-making, taking into account a patient’s expected health outcomes and well-being.This clinical practice guideline is nota replacement for clinical judgment or individualized, person-centered care;intended to be applied as inflexible standards of care across patients or patient populations by health care professionals, health systems, pharmacies, third-party payers, or governmental jurisdictions or to lead to the rapid tapering or abrupt discontinuation of opioids for patients;a law, regulation, or policy that dictates clinical practice or as a substitute for Food and Drug Administration–approved labeling;applicable to management of pain related to sickle cell disease,management of cancer-related pain, orpalliative care or end-of-life care; orfocused on opioids prescribed for opioid use disorder.CDC developed a draft clinical practice guideline on the basis of five systematic reviews of the best-available evidence on the benefits and risks of prescription opioids, nonopioid pharmacologic treatments, and nonpharmacologic treatments. The draft clinical practice guideline was reviewed by an independent federal advisory committee , peer reviewers, and the public and was revised after feedback from these reviews. Additional insights from patients, caregivers, and clinicians shared during virtual conversations held in 2020 were incorporated in the update. Importantly, to discourage the misapplication of opioid pain medication dosage thresholds as inflexible standards, revised recommendation statement language emphasizes principles such as avoiding increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients. More-specific considerations related to dosage have been moved to implementation considerations that follow each recommendation statement, where more nuance is offered to inform clinical decision-making and individualized patient care.This clinical practice guideline provides recommendations but does not replace clinical judgment and individualized, patient-centered decision-making. The recommendations are based on emerging evidence, including observational studies or randomized clinical trials with notable limitations; thus, they should be considered in the context of the clinician-patient relationship built on shared understanding and a whole-person approach that considers such factors as the patient’s physical and psychological functioning, support needs, expected health outcomes and well-being, home environment, and home and work responsibilities. Flexibility for clinicians and patients is paramount when making patient-centered clinical treatment decisions. The recommendations aim to improve communication between clinicians and patients about the benefits and risks of prescription opioids and other pain treatment strategies; improve the safety and effectiveness of pain treatment; improve pain, function, and quality of life for persons with pain; and reduce the risks associated with opioid pain treatment  and with other pain treatment.This clinical practice guideline provides voluntary clinical practice recommendations for clinicians that should not be used as inflexible standards of care. The recommendations are not intended to be implemented as absolute limits for policy or practice across populations by organizations, health care systems, or government entities.This clinical practice guideline is intended for clinicians who are treating outpatients aged ≥18 years with acute (duration of <1 month), subacute (duration of 1–3 months), or chronic (duration of >3 months) pain, and excludes pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care. The recommendations are most relevant to clinicians whose scope of practice includes prescribing opioids . Because clinicians might work within team-based care, this clinical practice guideline also refers to and promotes integrated pain management and collaborative working relationships among clinicians . This guideline update includes recommendations for primary care clinicians  and other clinicians managing pain in outpatient settings . Applicable settings include clinician offices, clinics, and urgent care centers. The recommendations do not apply to care provided to patients who are hospitalized or in an emergency department or other observational setting from which they might be admitted to inpatient care. These recommendations do apply to prescribing for pain management for patients when they are discharged from hospitals, emergency departments, or other facilities.In addition to updating recommendations on the basis of new evidence regarding management of chronic pain, this clinical practice guideline is intended to assist clinicians in weighing benefits and risks of prescribing opioid pain medication for painful acute conditions  and pain related to procedures . In 2020, several of these indications were prioritized by an ad hoc committee of the National Academies of Sciences, Engineering, and Medicine  and dentists (8.6%), account for considerable proportions of prescriptions. Pain medicine and physical medicine and rehabilitation clinicians prescribe opioids at the highest rates, followed by orthopedic and family medicine clinicians  and in populations with conditions posing special risks . The recommendations do not address the use of opioid pain medication in children or adolescents aged <18 years. The available evidence concerning the benefits and risks of long-term opioid therapy in children and adolescents remains limited, and few opioid medications provide information in their labeling regarding safety and effectiveness in pediatric patients. Guidelines and recommendations are available for pain management in children with sickle cell disease  Clinical Practice Guidelines in Oncology: Adult Cancer Pain  National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update Nonopioid therapies are at least as effective as opioids for many common types of acute pain. Clinicians should maximize use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider opioid therapy for acute pain if benefits are anticipated to outweigh risks to the patient. Before prescribing opioid therapy for acute pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy .Nonopioid therapies are preferred for subacute and chronic pain. Clinicians should maximize use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider initiating opioid therapy if expected benefits for pain and function are anticipated to outweigh risks to the patient. Before starting opioid therapy for subacute or chronic pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy, should work with patients to establish treatment goals for pain and function, and should consider how opioid therapy will be discontinued if benefits do not outweigh risks .Selecting Opioids and Determining Opioid Dosages When starting opioid therapy for acute, subacute, or chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release and long-acting (ER/LA) opioids .When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the lowest effective dosage. If opioids are continued for subacute or chronic pain, clinicians should use caution when prescribing opioids at any dosage, should carefully evaluate individual benefits and risks when considering increasing dosage, and should avoid increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients .For patients already receiving opioid therapy, clinicians should carefully weigh benefits and risks and exercise care when changing opioid dosage. If benefits outweigh risks of continued opioid therapy, clinicians should work closely with patients to optimize nonopioid therapies while continuing opioid therapy. If benefits do not outweigh risks of continued opioid therapy, clinicians should optimize other therapies and work closely with patients to gradually taper to lower dosages or, if warranted based on the individual circumstances of the patient, appropriately taper and discontinue opioids. Unless there are indications of a life-threatening issue such as warning signs of impending overdose , opioid therapy should not be discontinued abruptly, and clinicians should not rapidly reduce opioid dosages from higher dosages .Deciding Duration of Initial Opioid Prescription and Conducting Follow-Up (Recommendations 6 and 7)When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids .Clinicians should evaluate benefits and risks with patients within 1–4 weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation. Clinicians should regularly reevaluate benefits and risks of continued opioid therapy with patients .Assessing Risk and Addressing Potential Harms of Opioid Use Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms and discuss risk with patients. Clinicians should work with patients to incorporate into the management plan strategies to mitigate risk, including offering naloxone .When prescribing initial opioid therapy for acute, subacute, or chronic pain, and periodically during opioid therapy for chronic pain, 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 combinations that put the patient at high risk for overdose .When prescribing opioids for subacute or chronic pain, clinicians should consider the benefits and risks of toxicology testing to assess for prescribed medications as well as other prescribed and nonprescribed controlled substances .Clinicians should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently and consider whether benefits outweigh risks of concurrent prescribing of opioids and other central nervous system depressants .Clinicians should offer or arrange treatment with evidence-based medications to treat patients with opioid use disorder. Detoxification on its own, without medications for opioid use disorder, is not recommended for opioid use disorder because of increased risks for resuming drug use, overdose, and overdose death .Recommendation categories .Category A recommendation: Applies to all persons; most patients should receive the recommended course of action.Category B recommendation: Individual decision-making needed; different choices will be appropriate for different patients. Clinicians help patients arrive at a decision consistent with patient values and preferences and specific clinical situations.Evidence types .Type 1 evidence: Randomized clinical trials or overwhelming evidence from observational studies.Type 2 evidence: Randomized clinical trials with important limitations, or exceptionally strong evidence from observational studies.Type 3 evidence: Observational studies or randomized clinical trials with notable limitations.Type 4 evidence: Clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations.https://stacks.cdc.gov/view/cdc/121663). Evidence was categorized into the following types: type 1 , type 2 , type 3 , or type 4 . When no studies were available or the evidence was too limited to estimate effects, evidence was assessed as insufficient. Results from meta-analyses conducted for the AHRQ reviews were reported when available; otherwise, the evidence was synthesized qualitatively.The AHRQ approach uses a different method and terminology  to grade the strength of evidence from the ACIP adapted GRADE method  (https://www.gradeworkinggroup.org). Recommendations are based on the reviewed evidence. In the ACIP adapted GRADE framework, recommendations are assigned one of two categories (category A or B). Four major factors determine the category of the recommendation: 1) the quality of evidence, 2) the balance between desirable and undesirable effects, 3) values and preferences, and 4) resource allocation  .CDC sought recommendations on the draft clinical practice guideline from one of its federal advisory committees, the Board of Scientific Counselors of the National Center for Injury Prevention and Control (BSC/NCIPC). BSC/NCIPC advises the U.S. Department of Health and Human Services (HHS) Secretary, the CDC Director, and the NCIPC Director and makes recommendations regarding scientific, programmatic, and research policies, strategies, objectives, projects, and priorities. BSC/NCIPC also reviews progress toward injury and violence prevention. BSC/NCIPC members are special government employees appointed by the HHS Secretary or their designee as CDC advisory committee members. Members are required to complete the Office of Government Ethics Form 450 annually to disclose relevant interests and report on their disclosures during meetings. Disclosures for BSC/NCIPC are reported in this clinical practice guideline. Meeting minutes and documents for public BSC/NCIPC meetings are available on the BSC/NCIPC website  and provided a presentation on the background for updating the clinical practice guideline. CDC then requested the formation of an Opioid Workgroup (OWG), under the parent BSC, whose primary purpose would be to review a draft clinical practice guideline and to develop a report of their observations for BSC/NCIPC  directly affected by the clinical practice guideline, 2) directly involved with implementing or integrating recommendations into current practice, and 3) qualified to represent a specific discipline or expertise in alignment with the tasks of the workgroup for consideration by BSC/NCIPC. Identified groups with perspectives that would support the workgroup’s capacity included, but were not limited to, patients with pain, family members and caregivers, clinicians, public health practitioners, and research scientists. CDC announced the call for nominations at the December 4–5, 2019, public meeting and heard recommendations from the public during the public comment opportunities, as well as from BSC/NCIPC members, regarding recommendations for nominations. Persons interested in being considered for the workgroup were encouraged to submit self-nominations from December 4, 2019, through February 4, 2020. CDC’s BSC/NCIPC received 255 nominations for OWG.After reviewing clinical expertise, professional credentials, and diversity in perspectives of all nominees , OWG’s Designated Federal Officer (DFO) created a list of prospective workgroup members and sent them invitations to participate, along with conflict of interest disclosure forms. OWG’s DFO and BSC/NCIPC’s DFO reviewed conflict of interest disclosure forms. CDC’s Strategic Business Initiatives Unit (SBIU), which oversees the Federal Advisory Committee Act program, also reviewed the OWG Terms of Reference, prospective OWG roster, curricula vitae, and conflict of interest disclosure forms and determined all reported financial or other conflicts of interest were not present or nonsignificant before finalizing selection.Federal Register 85 FR 30709; 85 FR 40290).OWG had 23 members . After hearing additional CDC presentations on the process and progress of the draft clinical practice guideline, discussion of the OWG report, and a 2-hour public comment period, BSC/NCIPC voted unanimously that CDC adopt the OWG report, while considering ideas and suggestions raised by BSC/NCIPC and the public during the meeting, and that OWG’s work be considered complete and that OWG be sunsetted. BSC/NCIPC provided their recommendations to HHS and CDC on July 20, 2021. CDC considered OWG’s observations, BSC/NCIPC recommendations, and public comments during BSC/NCIPC meetings when revising the draft clinical practice guideline  at the National Institutes of Health (NIH), the Substance Abuse and Mental Health Services Administration (SAMHSA), FDA, and the Indian Health Service (IHS). BSC/NCIPC included ex officio members from the Administration for Children and Families; the Administration on Aging in the Administration for Community Living; the National Institute for Occupational Safety and Health and the National Center for Health Statistics at CDC; the Health Resources and Services Administration; IHS; SAMHSA; and the National Institute on Aging, the National Institute of Child Health and Human Development, NIDA, and the National Institute of Mental Health at NIH. Additional federal partners were engaged throughout the clinical practice guideline update process. Federal partners reviewed the full draft clinical practice guideline as part of CDC’s agency clearance process.Federal Register notices to better understand community members’ experiences and perspectives related to pain and pain management options before drafting the clinical practice guideline  posted from April 17, 2020, through June 16, 2020, CDC invited input specifically on topics focused on using or prescribing opioid pain medications, nonopioid medications, or nonpharmacologic treatments and received 5,392 public comments. Public comments were synthesized into common themes, using a CDC-funded analysis contract, and reviewed by CDC.CDC sought input through https://lab.opm.gov) worked with CDC to design and implement community engagement opportunities. These opportunities were designed to gain additional insight into the values and preferences of groups including patients with acute or chronic pain, patients’ family members or caregivers, and clinicians who care for patients with pain or conditions that can complicate pain management .In addition, the Lab at the U.S. Office of Personnel Management (OPM)  from July 22, 2020, through August 21, 2020, to solicit input from patients, caregivers, and clinicians interested in participating in individual conversations. After the Federal Register notice closed, CDC and OPM randomly selected participants within each group  from 973 respondents. CDC and OPM also developed a randomly selected waiting list of participants to fill conversation appointments that were missed or canceled by participants. The community engagement was authorized under the Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery (OMB Control Number 0920–1050) approval for the Paperwork Reduction Act. CDC and OPM conducted telephone and video conversations throughout September 2020 and spoke with 106 persons, including 42 patients, 21 caregivers, and 43 clinicians. Participants lived and worked all over the United States and had diverse experiences with opioids. Participants provided verbal consent for their conversations to be recorded. A transcription service reviewed the conversation recordings to develop anonymized transcripts. CDC and OPM reviewed the anonymized transcripts to develop thematic summaries.CDC planned to have in-person individual conversations with patients, caregivers, and clinicians but pivoted to holding conversations with persons in a virtual format because of the COVID-19 pandemic. CDC posted a companion CDC and OPM also held two human-centered codesign workshops with staff from CDC and the Centers for Medicare & Medicaid Services. Workshop topics included framing priority needs for public input; objectives for individual conversations; and synthesizing engagement strategies on the basis of insights from public comments and conversations with patients, caregivers, and clinicians. Workshop participants included HHS staff who were themselves patients, caregivers, clinicians, clinical practice guideline authors, and other subject matter experts.Federal Register notices  and NCIPC newsletters.CDC also gathered input through oral and written public comment opportunities at and in conjunction with public BSC/NCIPC meetings. These public comment opportunities were announced through Federal Register for public comment . The public comment period was open for 60 days . The Federal Docket received approximately 5,500 unique comments  from the public, including patients with acute and chronic pain, caregivers, and clinicians, and organizational perspectives from medical associations, professional organizations, academic institutions, state and local governments, and advocacy and industry groups. CDC reviewed and considered all public comments when revising the clinical practice guideline.CDC reviewed thematic summaries of public comments, individual conversations, and workshops to learn more about values and preferences of patients, caregivers, clinicians, and experts before drafting the clinical practice guideline (https://www.whitehouse.gov/wp-content/uploads/2019/04/M-19-15.pdf).This clinical practice guideline provides influential scientific information that could have a clear and substantial effect on public- and private-sector decisions. Therefore, peer review of the draft clinical practice guideline was required per the final information quality bulletin for peer review , subacute (duration of 1–3 months), or chronic (duration of >3 months) pain, excluding pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care . The recCategory A recommendations indicate that most patients should receive the recommended course of action; category B recommendations indicate that different choices will be appropriate for different patients, requiring clinicians to help patients arrive at a decision consistent with patient values and preferences and specific clinical situations. Consistent with the ACIP  antidepressants, pregabalin or gabapentin, and nonsteroidal anti-inflammatory drugs (NSAIDs), are associated with small to moderate improvements in chronic pain and function. Drug class–specific adverse events include serious cardiovascular, gastrointestinal, or renal effects with NSAIDs and sedation with anticonvulsants Nonopioid therapies are at least as effective as opioids for many common types of acute pain. Clinicians should maximize use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider opioid therapy for acute pain if benefits are anticipated to outweigh risks to the patient. Before prescribing opioid therapy for acute pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy .Nonopioid therapies are at least as effective as opioids for many common acute pain conditions, including low back pain, neck pain, pain related to other musculoskeletal injuries , pain related to minor surgeries typically associated with minimal tissue injury and mild postoperative pain , dental pain, kidney stone pain, and headaches including episodic migraine.Clinicians should maximize use of nonopioid pharmacologic  and nonpharmacologic  therapies as appropriate for the specific condition.Opioid therapy has an important role for acute pain related to severe traumatic injuries (including crush injuries and burns), invasive surgeries typically associated with moderate to severe postoperative pain, and other severe acute pain when NSAIDs and other therapies are contraindicated or likely to be ineffective.When diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe immediate-release opioids (see Recommendation 3) at the lowest effective dose (see Recommendation 4) and for no longer than the expected duration of pain severe enough to require opioids (see Recommendation 6).Clinicians should prescribe and advise opioid use only as needed  rather than on a scheduled basis  and encourage and recommend an opioid taper if opioids are taken around the clock for more than a few days (see Recommendation 6).If patients already receiving opioids long term require additional medication for acute pain, nonopioid medications should be used when possible and, if additional opioids are required , they should be continued only for the duration of pain severe enough to require additional opioids, returning to the patient’s baseline opioid dosage as soon as possible, including a taper to baseline dosage if additional opioids were used around the clock for more than a few days (see Recommendation 6).Clinicians should ensure that patients are aware of expected benefits of, common risks of, serious risks of, and alternatives to opioids before starting or continuing opioid therapy and should involve patients meaningfully in decisions about whether to start opioid therapy.Evaluation of the patient is critical to appropriate management. Evaluation can identify reversible causes of pain and underlying etiologies with potentially serious sequelae that require urgent action. To guide patient-specific selection of therapy, clinicians should evaluate patients and establish or confirm the diagnosis. Diagnosis can help identify interventions to reverse, ameliorate, or prevent worsening of pain and improve function   recommends nonpharmacologic treatment with superficial heat, massage, acupuncture, or spinal manipulation as a cornerstone of treatment for acute low back pain , dental pain, postoperative pain, and kidney stone pain; triptans, NSAIDs, or their combinations should be used along with antiemetics as needed for acute pain related to episodic migraine. NSAID use has been associated with serious gastrointestinal events and major coronary events  recommends stepwise, multimodal, shared decision-making, incorporating pharmacologic treatments that might include opioids. After vaginal delivery, ACOG recommends acetaminophen or NSAIDs, and if needed, adding an opioid. After cesarean delivery, ACOG recommends standard oral and parenteral medications such as acetaminophen, NSAIDs, or low-dose, low-potency, short-acting opioids with duration of opioid use limited to the shortest reasonable course expected for treating acute pain  if choosing pharmacologic treatment , pain related to minor surgeries typically associated with minimal tissue injury and only mild postoperative pain , dental pain, kidney stone pain, and headaches including episodic migraine. Opioid therapy has an important role for acute pain related to severe traumatic injuries (including crush injuries and burns), invasive surgeries typically associated with moderate to severe postoperative pain, and other severe acute pain when NSAIDs and other therapies are contraindicated or likely to be ineffective.When diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe immediate-release opioids (see Recommendation 3) at the lowest effective dose (see Recommendation 4) and for no longer than the expected duration of pain severe enough to require opioids (see Recommendation 6) to minimize unintentional initiation of long-term opioid use. Clinicians should maximize use of nonopioid pharmacologic  and nonpharmacologic  therapies as appropriate for the specific condition and continue these therapies as needed after opioids are discontinued. Clinicians should work with patients to prevent prolonged opioid use, prescribe and advise opioid use only as needed  rather than on a scheduled basis , and encourage and include an opioid taper if opioids will be taken around the clock for more than a few days (see Recommendation 6). Clinicians should consider concurrent medical conditions, including sleep apnea, pregnancy, renal or hepatic insufficiency, mental health conditions, and substance use disorders, in assessing risks of opioid therapy (see Recommendation 8); offer naloxone, particularly if the patient or a household member has risk factors for opioid overdose (see Recommendation 8); use particular caution when prescribing benzodiazepines or other sedating medications with opioid pain medication (see Recommendation 11); and check the prescription drug monitoring program (PDMP) database to ensure a new opioid prescription will not contribute to cumulative opioid dosages or medication combinations that put the patient at risk for overdose (see Recommendation 9). If signs of opioid use disorder are present, clinicians should address concerns with the patient, offer or arrange medication treatment for patients who meet criteria for opioid use disorder, and use nonpharmacologic and pharmacologic treatments as appropriate to manage the patient’s pain  .Review communication mechanisms and protocols patients can use to tell clinicians of severe or uncontrolled pain and to arrange for timely reassessment and management.Advise patients about serious adverse effects of opioids, including potentially fatal respiratory depression and development of a potentially serious opioid use disorder (see Recommendation 12) that can cause distress and inability to fulfill major role obligations at work, school, or home.Advise patients about common effects of opioids, such as constipation, dry mouth, nausea, vomiting, drowsiness, confusion, tolerance, physical dependence, and withdrawal symptoms when stopping opioids. To prevent constipation associated with opioid use, advise patients to increase hydration and fiber intake and to maintain or increase physical activity as they are able. Prophylactic pharmacologic therapy  might be needed to ensure regular bowel movements if opioids are used for more than a few days. Stool softeners or fiber laxatives without another laxative should be avoided. To minimize withdrawal symptoms, clinicians should provide and discuss an opioid tapering plan when opioids will be used around the clock for more than a few days (see Recommendation 6). Limiting opioid use to the minimum needed to manage pain  can help limit development of tolerance and therefore withdrawal after opioids are discontinued.If formulations are prescribed that combine opioids with acetaminophen, advise patients of the risks of taking additional over-the-counter products containing acetaminophen.To help patients assess when a dose of opioids is needed, explain that the goal is to reduce pain to make it manageable rather than to eliminate pain.Discuss effects that opioids might have on a person’s ability to safely operate a vehicle or other machinery, particularly when opioids are initiated or when other central nervous system depressants  are used concurrently.Discuss the potential for workplace toxicology testing programs to detect therapeutic opioid use.Discuss increased risks for opioid use disorder, respiratory depression, and death at higher dosages, along with the importance of taking only the amount of opioids prescribed .Review increased risks for respiratory depression when opioids are taken with benzodiazepines, other sedatives, alcohol, nonprescribed or illicit drugs , or other opioids (see Recommendations 8 and 11).Discuss risks to household members and other persons if opioids are intentionally or unintentionally shared with others for whom they are not prescribed, including the possibility that others might experience overdose at the same or lower dosage than prescribed for the patient and that young children and pets are susceptible to unintentional ingestion. Discuss storage of opioids in a secure and preferably locked location, options for safe disposal of unused opioids  and clinician use of PDMP information (see Recommendation 9).Nonopioid therapies are preferred for subacute and chronic pain. Clinicians should maximize use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider initiating opioid therapy if expected benefits for pain and function are anticipated to outweigh risks to the patient. Before starting opioid therapy for subacute or chronic pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy, should work with patients to establish treatment goals for pain and function, and should consider how opioid therapy will be discontinued if benefits do not outweigh risks .To guide patient-specific selection of therapy, clinicians should evaluate patients and establish or confirm the diagnosis.Clinicians should recommend appropriate noninvasive nonpharmacologic approaches to help manage chronic pain, such as exercise  or exercise therapy  for back pain, fibromyalgia, and hip or knee osteoarthritis; weight loss for knee osteoarthritis; manual therapies for hip osteoarthritis; psychological therapy, spinal manipulation, low-level laser therapy, massage, mindfulness-based stress reduction, yoga, acupuncture, and multidisciplinary rehabilitation for low back pain; mind-body practices , massage, and acupuncture for neck pain; cognitive behavioral therapy, myofascial release massage, mindfulness practices, tai chi, qigong, acupuncture, and multidisciplinary rehabilitation for fibromyalgia; and spinal manipulation for tension headache.Low-cost options to integrate exercise include walking in public spaces or use of public recreation facilities for group exercise. Physical therapy can be helpful, particularly for patients who have limited access to safe public spaces or public recreation facilities for exercise or whose pain has not improved with low-intensity physical exercise.Health insurers and health systems can improve pain management and reduce medication use and associated risks by increasing reimbursement for and access to noninvasive nonpharmacologic therapies with evidence for effectiveness.Clinicians should review FDA-approved labeling, including boxed warnings, and weigh benefits and risks before initiating treatment with any pharmacologic therapy.When patients affected by osteoarthritis have an insufficient response to nonpharmacologic interventions such as exercise for arthritis pain, topical NSAIDs can be used in patients with pain in a single or few joints near the surface of the skin . For patients with osteoarthritis pain in multiple joints or incompletely controlled with topical NSAIDs, duloxetine or systemic NSAIDs can be considered.NSAIDs should be used at the lowest effective dose and shortest duration needed and should be used with caution, particularly in older adults and in patients with cardiovascular comorbidities, chronic renal failure, or previous gastrointestinal bleeding.When patients with chronic low back pain have had an insufficient response to nonpharmacologic approaches such as exercise, clinicians can consider NSAIDs or duloxetine for patients without contraindications.Tricyclic, tetracyclic, and SNRI antidepressants; selected anticonvulsants ; and capsaicin and lidocaine patches can be considered for neuropathic pain. In older adults, decisions to use tricyclic antidepressants should be made judiciously on a case-by-case basis because of risks for confusion and falls.Duloxetine and pregabalin are FDA-approved for the treatment of diabetic peripheral neuropathy, and pregabalin and gabapentin are FDA-approved for treatment of postherpetic neuralgia.In patients with fibromyalgia, tricyclic  and SNRI antidepressants , NSAIDs , and specific anticonvulsants  are used to improve pain, function, and quality of life. Duloxetine, milnacipran, and pregabalin are FDA-approved for the treatment of fibromyalgia. In older adults, decisions to use tricyclic antidepressants should be made judiciously on a case-by-case basis because of risks for confusion and falls.Patients with co-occurring pain and depression might be especially likely to benefit from antidepressant medication (see Recommendation 8).Opioids should not be considered first-line or routine therapy for subacute or chronic pain. This does not mean that patients should be required to sequentially fail nonpharmacologic and nonopioid pharmacologic therapy or be required to use any specific treatment before proceeding to opioid therapy. Rather, expected benefits specific to the clinical context should be weighed against risks before initiating therapy. In some clinical contexts , opioids might be appropriate regardless of previous therapies used. In other situations , expected benefits of initiating opioids are unlikely to outweigh risks regardless of previous nonpharmacologic and nonopioid pharmacologic therapies used.Opioid therapy should not be initiated without consideration by the clinician and patient of an exit strategy to be used if opioid therapy is unsuccessful.Before opioid therapy is initiated for subacute or chronic pain, clinicians should determine jointly with patients how functional benefit will be evaluated and establish specific, measurable treatment goals.For patients with subacute pain who started opioid therapy for acute pain and have been treated with opioid therapy for ≥30 days, clinicians should ensure that potentially reversible causes of chronic pain are addressed and that opioid prescribing for acute pain does not unintentionally become long-term opioid therapy simply because medications are continued without reassessment. Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which should occur only as an intentional decision that benefits are likely to outweigh risks after informed discussion between the clinician and patient and as part of a comprehensive pain management approach.Clinicians seeing new patients already receiving opioids should establish treatment goals, including functional goals, for continued opioid therapy. Clinicians should avoid rapid tapering or abrupt discontinuation of opioids (see Recommendation 5).Patient education and discussion before starting opioid therapy are critical so that patient preferences and values can be understood and used to inform clinical decisions.Clinicians should review available low-cost options for pain management for all patients and particularly for patients who have low incomes, do not have health insurance, or have inadequate insurance.Clinicians should ensure that patients are aware of expected benefits of, common risks of, serious risks of, and alternatives to opioids before starting or continuing opioid therapy and should involve patients in decisions about whether to start opioid therapy.To guide patient-specific selection of therapy, clinicians should evaluate patients and establish or confirm the diagnosis   and should weigh benefits and risks of use, dosage, and duration of NSAIDs when treating older adults and patients with hypertension, renal insufficiency, heart failure, or those with risk for peptic ulcer disease or cardiovascular disease. NSAIDs are potentially inappropriate for use in older adults with chronic pain because of higher risk for adverse effects with prolonged use , can improve pain and function without risk for serious harms  are used for painful symptoms in chronic pain conditions. Nonopioid pharmacologic therapies are associated with risks, particularly in older adults, pregnant patients, and patients with certain comorbidities such as cardiovascular, renal, gastrointestinal, and liver disease. For example, NSAID use has been associated with serious gastrointestinal events and major coronary events , with intermediate-term (6–12 months) evidence for certain medications (celecoxib and duloxetine) and evidence that duloxetine is more effective in older (>65 years) than younger patients and in patients with knee osteoarthritis , NSAIDs , and specific anticonvulsants   because of their anticholinergic effects (2: 71%) and function , opioids might be appropriate regardless of previous therapies used. In other situations , expected benefits of initiating opioids are unlikely to outweigh risks regardless of previous nonpharmacologic and nonopioid pharmacologic therapies used.Clinical evidence reviews found no instrument with high accuracy for predicting opioid-related harms, such as overdose or opioid use disorder . Although the clinical evidence reviews did not find studies evaluating the effectiveness of written agreements or treatment plans  is usually needed to ensure regular bowel movements if opioids are taken regularly. Stool softeners or fiber laxatives without another laxative should be avoided.If formulations are prescribed that combine opioids with acetaminophen, advise patients of the risks for taking additional over-the-counter products containing acetaminophen.Discuss effects that opioids might have on ability to safely operate a vehicle or other machinery, particularly when opioids are initiated, when dosages are increased, or when other central nervous system depressants, such as benzodiazepines or alcohol, are used concurrently.Discuss the potential for workplace toxicology testing programs to detect therapeutic opioid use.Discuss increased risks for opioid use disorder, respiratory depression, and death at higher dosages, along with the importance of taking only the amount of opioids prescribed .Review increased risks for respiratory depression when opioids are taken with benzodiazepines, other sedatives, alcohol, nonprescribed drugs such as heroin, or other opioids.Discuss risks for household members and other persons if opioids are intentionally or unintentionally shared with others for whom they are not prescribed, including the possibility that others might experience overdose at the same or at lower dosage than prescribed for the patient and that young children are susceptible to unintentional ingestion. Discuss storage of opioids in a secure, preferably locked location and options for safe disposal of unused opioids  and clinician use of PDMP information (see Recommendation 9) and toxicology screening (see Recommendation 10).Consider whether cognitive status might interfere with management of opioid therapy and, if so, determine whether a caregiver can responsibly comanage medication therapy. Discuss the importance of reassessing medication use over time with both the patient and caregiver, as appropriate.Because of the possibility that benefits of opioid therapy might diminish or that risks might become more prominent over time, clinicians should elicit patients’ experiences and preferences and review expected benefits and risks of continued opioid therapy with patients periodically (see Recommendation 7).Office-based interventional approaches, such as arthrocentesis and intra-articular glucocorticoid injection for pain associated with rheumatoid arthritis  also might be used. In some cases, medication combinations might provide complementary or synergistic benefits and facilitate lower dosing of individual medications, as has been demonstrated in trials of patients with neuropathic pain  opioids .Clinicians should not treat acute pain with ER/LA opioids or initiate opioid treatment for subacute or chronic pain with ER/LA opioids, and clinicians should not prescribe ER/LA opioids for intermittent or as-needed use.ER/LA opioids should be reserved for severe, continuous pain. FDA has noted that some ER/LA opioids should be considered only for patients who have received certain dosages of opioids of immediate-release opioids daily for at least 1 week.When changing to an ER/LA opioid for a patient previously receiving a different immediate-release opioid, clinicians should consult product labeling and reduce total daily dosage to account for incomplete opioid cross-tolerance.Clinicians should use additional caution with ER/LA opioids and consider a longer dosing interval when prescribing to patients with renal or hepatic dysfunction because decreased clearance of medications among these patients can lead to accumulation of drugs to toxic levels and persistence in the body for longer durations.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, including assessing risk for QT prolongation and considering electrocardiographic monitoring, should consider prescribing methadone for pain.Only clinicians who are familiar with the dosing and absorption properties of the ER/LA opioid transdermal fentanyl and are prepared to educate their patients about its use should consider prescribing it.ER/LA opioids include methadone, transdermal fentanyl, and extended-release versions of opioids such as oxycodone, hydromorphone, hydrocodone, and morphine. Clinical evidence reviews found that effects of opioids on short-term pain and function were generally consistent across duration of action (short- or long-acting) and opioid type , although five trials directly comparing different types of opioids found a mixed mechanism agent associated with greater pain relief versus a pure opioid agonist, with fewer nonserious adverse events  are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain and not used as as-needed pain relievers  of ER/LA opioids , clinicians should not prescribe ER/LA opioids for the treatment of acute pain. ER/LA opioids should be reserved for severe, continuous pain and should be considered only for patients who have received certain dosages of immediate-release opioids daily  for at least 1 week .The recommendations related to opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather, they are intended to be guideposts to help inform clinician-patient decision-making. Risks of opioid use, including risk for overdose and overdose death, increase continuously with dosage, and there is no single dosage threshold below which risks are eliminated. Therefore, the recommendation language emphasizes that clinicians should avoid increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients rather than emphasizing a single specific numeric threshold. Further, these recommendations apply specifically to starting opioids or to increasing opioid dosages, and a different set of benefits and risks applies to reducing opioid dosages (see Recommendation 5).When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the lowest effective dosage.For patients not already taking opioids, the lowest effective dose can be determined using product labeling as a starting point with calibration as needed based on the severity of pain and other clinical factors such as renal or hepatic insufficiency (see Recommendation 8).The lowest starting dose for opioid-naïve patients is often equivalent to a single dose of approximately 5–10 MME or a daily dosage of 20–30 MME/day. A listing of common opioid medications and their doses in MME equivalents is provided .TABLEMorIf opioids are continued for subacute or chronic pain, clinicians should use caution when prescribing opioids at any dosage and should generally avoid dosage increases when possible.Many patients do not experience benefit in pain or function from increasing opioid dosages to ≥50 MME/day but are exposed to progressive increases in risk as dosage increases. Therefore, before increasing total opioid dosage to ≥50 MME/day, clinicians should pause and carefully reassess evidence of individual benefits and risks. If a decision is made to increase dosage, clinicians should use caution and increase dosage by the smallest practical amount. The recommendations related to opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather, they are intended to be guideposts to help inform clinician-patient decision-making.Additional dosage increases beyond 50 MME/day are progressively more likely to yield diminishing returns in benefits for pain and function relative to risks to patients as dosage increases further. Clinicians should carefully evaluate a decision to further increase dosage on the basis of individualized assessment of benefits and risks and weighing factors such as diagnosis, incremental benefits for pain and function relative to risks with previous dosage increases, other treatments and effectiveness, and patient values and preferences. The recommendations related to opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather, they are intended to be guideposts to help inform clinician-patient decision-making.Benefits of high-dose opioids for pain are not well established. Few trials evaluated opioid dosages of ≥90 MME/day . The lowest starting dose for opioid-naïve patients is often equivalent to a single dose of approximately 5–10 MME or a daily dosage of 20–30 MME/day. A listing of common opioid medications and their doses in MME equivalents is provided . For exaClinicians should generally avoid unnecessary dosage increases, use caution when increasing opioid dosages, and increase dosage by the smallest practical amount because overdose risk increases with increases in opioid dosage. Although evidence to recommend specific intervals for dosage titration is limited, rapid dosage increases put patients at greater risk for sedation, respiratory depression, and overdose. For opioid-naïve outpatients with acute pain treated with an opioid for a few days or less, dosage increases are usually unnecessary and should not be attempted without close monitoring because of the risks for respiratory depression. In the context of long-term opioid use, when dosage is increased, clinicians should reevaluate patients after increasing dosage for changes in pain, function, and risk for harm (see Recommendation 7).Before increasing total opioid dosage to ≥50 MME/day, clinicians should pause, considering that dosage increases to >50 MME/day are unlikely to provide substantially improved pain control for most patients while overdose risk increases with dosage, and carefully reassess evidence of benefits and risks. If a patient’s opioid dosage for all sources of opioids combined reaches or exceeds 50 MME/day, clinicians should implement additional precautions, including increased frequency of follow-up (see Recommendation 7), and offer naloxone and overdose prevention education to both the patient and the patient’s household members (see Recommendation 8).Additional dosage increases beyond 50 MME/day are progressively more likely to yield diminishing returns in benefits for pain and function relative to risks to patients. Clinicians should carefully evaluate a decision to increase dosage after an individualized assessment of benefits and risks and weighing factors such as diagnosis, incremental benefits for pain and function relative to risks with previous dosage increases, other treatments and effectiveness, and patient values and preferences.Certain states require clinicians to implement clinical protocols at specific dosage levels. For example, before increasing long-term opioid therapy dosage to >120 MME/day, clinicians in Washington state must obtain consultation from a pain specialist who agrees that the increase is indicated and appropriate , opioid therapy should not be discontinued abruptly, and clinicians should not rapidly reduce opioid dosages from higher dosages .Clinicians should carefully weigh both the benefits and risks of continuing opioid medications and the benefits and risks of tapering opioids.If benefits outweigh risks of continued opioid therapy, clinicians should work closely with patients to optimize nonopioid therapies while continuing opioid therapy.When benefits (including avoiding risks of tapering) do not outweigh risks of continued opioid therapy, clinicians should optimize other therapies and work closely with patients to gradually taper to a reduced opioid dosage or, if warranted based on the individual clinical circumstances of the patient, appropriately taper and discontinue opioid therapy.In situations where benefits and risks of continuing opioids are considered to be close or unclear, shared decision-making with patients is particularly important.At times, clinicians and patients might not be able to agree on whether or not tapering is necessary. When patients and clinicians are unable to arrive at a consensus on the assessment of benefits and risks, clinicians should acknowledge this discordance, express empathy, and seek to implement treatment changes in a patient-centered manner while avoiding patient abandonment.Patient agreement and interest in tapering is likely to be a key component of successful tapers.For patients agreeing to taper to lower opioid dosages and for those remaining on higher opioid dosages, clinicians should establish goals with the patient for continued opioid therapy (see Recommendations 2 and 7) and maximize pain treatment with nonpharmacologic and nonopioid pharmacologic treatments as appropriate (see Recommendation 2).Clinicians should collaborate with the patient on the tapering plan, including patients in decisions such as how quickly tapering will occur and when pauses in the taper might be warranted.Clinicians should follow up frequently (at least monthly) with patients engaging in opioid tapering. Team members  can support the clinician and patient during the ongoing taper process through telephone contact, telehealth visits, or face-to-face visits.When opioids are reduced or discontinued, a taper slow enough to minimize symptoms and signs of opioid withdrawal  should be used.Longer duration of previous opioid therapy might require a longer taper. For patients who have taken opioids long-term , tapers can be completed over several months to years depending on the opioid dosage and should be individualized based on patient goals and concerns.When patients have been taking opioids for longer durations , tapers of 10% per month or slower are likely to be better tolerated than more rapid tapers.For patients struggling to tolerate a taper, clinicians should maximize nonopioid treatments for pain and should address behavioral distress.Clinically significant opioid withdrawal symptoms can signal the need to further slow the taper rate.At times, tapers might have to be paused and restarted again when the patient is ready and might have to be slowed as patients reach low dosages.Before reversing a taper, clinicians should carefully assess and discuss with the patient the benefits and risks of increasing opioid dosage.Goals of the taper might vary . If the clinician has determined with the patient that the ultimate goal of tapering is discontinuing opioids, after the smallest available dose is reached the interval between doses can be extended and opioids can be stopped when taken less frequently than once a day.Clinicians should access appropriate expertise if considering tapering opioids during pregnancy because of possible risks to the pregnant patient and the fetus if the patient goes into withdrawal.Clinicians should advise patients of an increased risk for overdose on abrupt return to a previously prescribed higher dose because of loss of opioid tolerance, provide opioid overdose education, and offer naloxone.Clinicians should remain alert to signs of and screen for anxiety, depression, and opioid misuse or opioid use disorder (see Recommendations 8 and 12) that might be revealed by an opioid taper and provide treatment or arrange for management of these comorbidities.Clinicians should closely monitor patients who are unable to taper and who continue on high-dose or otherwise high-risk opioid regimens  and should work with patients to mitigate overdose risk  (see Recommendation 8).Clinicians can use periodic and strategic motivational questions and statements to encourage movement toward appropriate therapeutic changes and functional goals.Clinicians have a responsibility to provide or arrange for coordinated management of patients’ pain and opioid-related problems, including opioid use disorder.Payers, health systems, and state medical boards should not use this clinical practice guideline to set rigid standards or performance incentives related to dose or duration of opioid therapy; should ensure that policies based on cautionary dosage thresholds do not result in rapid tapers or abrupt discontinuation of opioids; and should ensure that policies do not penalize clinicians for accepting new patients who are using prescribed opioids for chronic pain, including those receiving high dosages of opioids, or for refraining from rapidly tapering patients prescribed long-term opioid medications.Although Recommendation 5 specifically refers to patients using long-term opioid therapy for subacute or chronic pain, many of the principles in these implementation considerations and supporting rationale, including communication with patients, pain management, behavioral support, and slower taper rates, also are relevant when discontinuing opioids in patients who have received them for shorter durations (see Recommendations 6 and 7).Patients receiving long-term, high-dosage opioid therapy for chronic pain are at increased risk for adverse events including overdose death . Opioid therapy should be limited to circumstances where benefits of therapy outweigh risks. Because tapering opioids can be harmful in some circumstances, benefits of continuing opioids in patients who have already received them long-term might include avoiding risks of tapering and discontinuing opioids. In situations where benefits and risks of continuing opioids are considered to be close or unclear, shared decision-making with patients is particularly important. At times, clinicians and patients might not be able to agree on whether tapering is necessary. When patients and clinicians are unable to arrive at a consensus on the assessment of benefits and risks, clinicians should acknowledge this discordance, express empathy, and seek to implement treatment changes in a patient-centered manner while avoiding patient abandonment. Unless there is a life-threatening issue such as warning signs of an imminent overdose, the benefits of rapidly tapering or abruptly discontinuing opioids are unlikely to outweigh the substantial risks of these practices  might require tapering one or more medications to reduce risk for respiratory depression. Tapering decisions and plans should be coordinated with prescribers of all respiratory depressant medications (see Recommendation 11). Benzodiazepines should be tapered gradually because of risks  of benzodiazepine withdrawal  and the benefit-risk balance is unclear ,the patient is receiving higher opioid dosages without evidence of benefit from the higher dosage,the patient experiences side effects that diminish quality of life or impair function,evidence of opioid misuse exists,the patient experiences an overdose or other serious event  or has warning signs for an impending event , orthe patient is receiving medications  or has medical conditions  that increase risk for adverse outcomes.For patients already taking opioids long term (both established patients and patients transferring from other clinicians), the possibility of opioid dosage reduction might provoke substantial anxiety. In addition, tapering opioids after years of taking them can be especially challenging because of physical and psychological dependence. However, patients should be offered the opportunity to reevaluate their continued use of opioids. Clinicians should review benefits and risks of continued opioid therapy with empathy.Whenever possible, clinicians should collaborate with patients and share decision-making about whether and how to taper opioids. Clinicians should review benefits and risks of opioid therapy with the patient and decide whether tapering is appropriate for the patient. If the existing opioid regimen does not put the patient at imminent risk for overdose or other injury, tapering does not need to occur immediately, and clinicians can take time to reach agreement with patients . Integrating behavioral and nonopioid pain therapies before and during a taper can help manage pain  should be used. Tapers can be completed over several months to years depending on the opioid dosage and should be individualized based on patient goals and concerns. Longer durations of previous opioid therapy might require longer tapers. Evidence on optimal taper rate is emerging. Tapers of approximately 10% per month or slower are likely to be better tolerated than more rapid tapers when patients have been taking opioids for longer durations    criteria and, if criteria for opioid use disorder are met, offered evidence-based medication treatment (see Recommendation 12) and naloxone for opioid overdose reversal (see Recommendation 8).Some patients with unanticipated challenges to tapering, such as inability to make progress in tapering despite opioid-related harm, might have undiagnosed opioid use disorder. Therefore, patients experiencing such challenges should be assessed for opioid use disorder using Emerging evidence suggests that patients for whom risks of continued high-dose opioid use outweigh benefits but who are unable to taper and who do not meet criteria for opioid use disorder might benefit from transition to buprenorphine (https://pcssnow.org) offers training, technical assistance, and mentors to assist clinicians who are unfamiliar with initiation of buprenorphine and have additional questions about the diagnosis and treatment of opioid use disorder. Because the duration of action for analgesia is shorter than the duration of action for suppression of opioid withdrawal and stabilization of opioid use disorder  and should work with patients to mitigate overdose risk  (see Recommendation 8). Clinicians can use periodic and strategic motivational questions and statements to encourage movement toward appropriate therapeutic changes .Nontraumatic, nonsurgical acute pain can often be managed without opioids (see Recommendation 1).Opioids are sometimes needed for treatment of acute pain (see Recommendation 1). When the diagnosis and severity of acute pain warrant use of opioids, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. For many common causes of nontraumatic, nonsurgical pain, when opioids are needed, a few days or less are often sufficient, and shorter courses can minimize the need to taper opioids to prevent withdrawal symptoms at the end of a course of opioids. However, durations should be individualized to the patient’s clinical circumstances.Clinicians should generally avoid prescribing additional opioids to patients just in case pain continues longer than expected.For postoperative pain related to major surgery, procedure-specific opioid prescribing recommendations are available with ranges for amounts of opioids needed .To minimize unintended effects on patients, clinicians, practices, and health systems should have mechanisms in place for the subset of patients who experience severe acute pain that continues longer than the expected duration. These mechanisms should allow for timely reevaluation to confirm or revise the initial diagnosis and adjust pain management accordingly. Clinicians, practices, and health systems can help minimize disparities in access to and affordability of care and refills by ensuring all patients can obtain and afford additional evaluation and treatment, as needed.Longer durations of opioid therapy are more likely to be needed when the mechanism of injury is expected to result in prolonged severe pain .Patients should be evaluated at least every 2 weeks if they continue to receive opioids for acute pain.If opioids are continued for ≥1 month, clinicians should ensure that potentially reversible causes of chronic pain are addressed and that opioid prescribing for acute pain does not unintentionally become long-term opioid therapy simply because medications are continued without reassessment. Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which should occur only as an intentional decision that benefits are likely to outweigh risks after discussion between the clinician and patient and as part of a comprehensive pain management approach. Clinicians should refer to recommendations on subacute and chronic pain for initiation (Recommendation 2), follow-up (Recommendation 7), and tapering (Recommendation 5) of ongoing opioid therapy.If patients already receiving long-term opioid therapy require additional opioids for superimposed severe acute pain , opioids should be continued only for the duration of pain severe enough to require additional opioids, returning to the patient’s baseline opioid dosage as soon as possible, including a taper to baseline dosage if additional opioids were used around the clock for more than a few days.If opioids are used continuously (around the clock) for more than a few days for acute pain, clinicians should prescribe a brief taper to minimize withdrawal symptoms on discontinuation of opioids.If a taper is needed, taper durations might need to be adjusted depending on the duration of the initial opioid prescription .Tapering plans should be discussed with the patient before hospital discharge and with clinicians coordinating the patient’s care as an outpatient. (See Recommendation 5 for tapering considerations when patients have taken opioids continuously for >1 month.)Data suggest that pain improves within days for many patients with common types of acute pain in primary care or emergency department settings. Analysis of nationwide U.S. commercial insurance claims in 2014 found median durations of initial opioid analgesic prescriptions for acute pain indications in primary care settings were 4–7 days . When the diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. A few days or less are often sufficient when opioids are needed for many common causes of nonsurgical acute pain, and limiting the duration of opioid therapy can minimize the need to taper to prevent withdrawal symptoms at the end of the course of opioids and limit unused opioids. Certain circumstances  might require use of opioids for durations of >7 days. Durations should be individualized based on the patient’s clinical circumstances.When patients are discharged from the hospital after surgery, the course and dosage of any opioid medications administered during hospitalization and before discharge can help predict ongoing pain management needs  to obtain additional medication as needed, leading to potential disparities in treatment. Clinicians, practices, and health systems should have mechanisms in place for the subset of patients who experience severe acute pain that continues longer than the expected duration. These mechanisms should allow for timely reevaluation to confirm or revise the initial diagnosis and adjust pain management accordingly. In particular, clinicians, practices, and health systems should ensure all patients can obtain and afford additional evaluation and treatment as needed to minimize disparities in access to and affordability of care and refills.Patients should be evaluated at least every 2 weeks if they continue to receive opioids for acute pain. If opioids are continued for ≥1 month, clinicians should ensure that potentially reversible causes of chronic pain are addressed and that opioid prescribing for acute pain does not unintentionally become long-term opioid therapy simply because medications are continued without reassessment. Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which should occur only as an intentional decision that benefits are likely to outweigh risks after discussion between the clinician and patient and as part of a comprehensive pain management approach. Clinicians should refer to recommendations on subacute and chronic pain for initiation (Recommendation 2), follow-up (Recommendation 7), and tapering (Recommendation 5) of ongoing opioid therapy. If patients already receiving long-term opioids require additional opioids for superimposed severe acute pain , opioids should be continued only for the duration of pain severe enough to require additional opioids, returning to the patient’s baseline opioid dosage as soon as possible, including a taper to baseline dosage if additional opioids were used around the clock for more than a few days.If opioids are used continuously (around the clock) for more than a few days for acute pain, clinicians should prescribe a brief taper to minimize withdrawal symptoms on discontinuation of opioids. Taper durations might need to be adjusted depending on the duration of the initial opioid prescription. For example, if opioids are used continuously for >3 days but for <1 week, clinicians can consider reducing the daily dosage to 50% for 2 days to ameliorate withdrawal symptoms when discontinuing opioids. When patients have taken opioids continuously for ≥1 week but <1 month, clinicians might consider a slower taper  .In addition to evaluating benefits and risks of opioids before starting opioid therapy (see Recommendation 2), clinicians should evaluate patients to assess benefits and risks of opioids within 1–4 weeks of starting long-term opioid therapy or of dosage escalation.Clinicians should consider follow-up intervals within the lower end of this range when ER/LA opioids are started or increased, because of the increased risk for overdose within the first 2 weeks of treatment, or when total daily opioid dosage is ≥50 MME/day. (Overdose risk is doubled across multiple studies for dosages of 50 to <100 MME/day relative to <20 MME/day.) (See Recommendation 4.)Shorter follow-up intervals (every 2–3 days for the first week) should be strongly considered when starting or increasing the dosage of methadone, because of the variable half-life of this drug (see Recommendation 3) and the potential for drug accumulation during initiation and during upward titration of dosage.An initial follow-up interval closer to 4 weeks can be considered when starting immediate-release opioids at a dosage of <50 MME/day.Clinicians should follow up with and evaluate patients with subacute pain who started opioid therapy for acute pain and have been treated with opioid therapy for 30 days to reassess the patient’s pain, function, and treatment course; ensure that potentially reversible causes of chronic pain are addressed; and prevent unintentional initiation of long-term opioid therapy. Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which should occur only as an intentional decision that benefits are likely to outweigh risks after discussion between the clinician and patient and as part of a comprehensive pain management approach (see Recommendation 2).Clinicians should regularly reassess all patients receiving long-term opioid therapy, including patients who are new to the clinician but on long-term opioid therapy, with a suggested interval of every 3 months or more frequently for most patients.Clinicians seeing new patients already receiving opioids should establish treatment goals, including functional goals, for continued opioid therapy (see Recommendation 2).Clinicians should reevaluate patients who are at higher risk for opioid use disorder or overdose  more frequently than every 3 months. Clinicians should regularly screen all patients for these conditions, which can change during the course of treatment (see Recommendation 8).Clinicians, practices, and health systems can help minimize unintended effects on patients by ensuring all patients can access and afford follow-up evaluation.In practice contexts where virtual visits are part of standard care , or for patients for whom in-person follow-up visits are challenging , follow-up assessments that allow the clinician to communicate with and observe the patient through telehealth modalities might be conducted.At follow-up, clinicians should review patient perspectives and goals, determine whether opioids continue to meet treatment goals, including sustained improvement in pain and function, and determine whether the patient has experienced common or serious adverse events or early warning signs of serious adverse events or has signs of opioid use disorder.Clinicians should ensure that treatment for depression, anxiety, or other psychological comorbidities is optimized.Clinicians should ask patients about their preferences for continuing opioids, considering their effects on pain and function relative to any adverse effects experienced. If risks outweigh benefits of continued opioid therapy , clinicians should work with patients to taper and reduce opioid dosage or taper and discontinue opioids when possible (see from Recommendation 5).Clinicians should maximize pain treatment with nonpharmacologic and nonopioid pharmacologic treatments as appropriate (see Recommendation 2).Although clinical evidence reviews did not find studies evaluating the effectiveness of more frequent monitoring intervals  or payer issues  could have consequences when recommending frequent visits and should be considered.Clinicians should evaluate patients to assess benefits and risks of opioids within 1–4 weeks of starting long-term opioid therapy or of dosage escalation. Clinicians should consider follow-up intervals within the lower end of this range when ER/LA opioids are started or increased, because of the increased risk for overdose within the first 2 weeks of treatment .In analyses of placebo-controlled trials, the clinical evidence reviews found that effects of opioids on mean improvement in pain and in function were greater at 1–3 months than at 3–6 months ; determine whether benefits of opioids continue to outweigh risks; and determine whether there is a need for opioid dosage reduction or discontinuation. Clinicians should assess benefits in function, pain control, and quality of life by asking patients about progress toward person-centered functional goals that have meaning for them (see Recommendation 2) or by using tools such as the three-item PEG assessment scale , clinicians should work with patients to taper and reduce opioid dosage or to taper and discontinue opioids when possible (see Recommendation 5). Clinicians should maximize pain treatment with nonpharmacologic and nonopioid pharmacologic treatments as appropriate (see Recommendation 2).Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms and discuss risk with patients. Clinicians should work with patients to incorporate into the management plan strategies to mitigate risk, including offering naloxone .Clinicians should ask patients about their drug and alcohol use and use validated tools or consult with behavioral specialists to screen for and assess mental health and substance use disorders.When considering initiating long-term opioid therapy, clinicians should ensure that treatment for depression and other mental health conditions is optimized, consulting with behavioral health specialists when needed.Clinicians should offer naloxone when prescribing opioids, particularly to patients at increased risk for overdose, including patients with a history of overdose, patients with a history of substance use disorder, patients with sleep-disordered breathing, patients taking higher dosages of opioids , patients taking benzodiazepines with opioids (see Recommendation 11), and patients at risk for returning to a high dose to which they have lost tolerance .Practices should educate patients on overdose prevention and naloxone use and offer to provide education to members of their households.Naloxone coprescribing can be facilitated by clinics or practices with resources to provide naloxone training, by collaborative practice models with pharmacists, or through statewide protocols or standing orders for naloxone at pharmacies.https://prescribetoprevent.org. Additional resources are at https://www.samhsa.gov.Resources for prescribing naloxone in primary care and emergency department settings can be found through Prescribe to Prevent at In part because of concerns about cost of naloxone and access for some patients and reports that purchasing of naloxone has in some cases been required to fill opioid prescriptions, including for patients without a way to afford naloxone, this recommendation specifies that naloxone should be offered to patients. To that end, clinicians, health systems, and payers can work to ensure patients can obtain naloxone, a potentially lifesaving treatment.Clinicians should avoid prescribing opioids to patients with moderate or severe sleep-disordered breathing when possible to minimize risk for respiratory depression.When making decisions about whether to initiate opioid therapy for pain during pregnancy, clinicians and patients together should carefully weigh benefits and risks. For pregnant persons already receiving opioids, clinicians should access appropriate expertise if tapering is being considered because of possible risks to the pregnant patient and the fetus if the patient goes into withdrawal (see Recommendation 5).For pregnant persons with opioid use disorder, medication for opioid use disorder (buprenorphine or methadone) is the recommended therapy and should be offered as early as possible in pregnancy to prevent harms to both the patient and the fetus (see Recommendation 12).Clinicians should use additional caution and increased monitoring (see Recommendation 7) to minimize risks of opioids prescribed for patients with renal or hepatic insufficiency and for patients aged ≥65 years. Clinicians should implement interventions to mitigate common risks of opioid therapy among older adults, such as exercise or bowel regimens to prevent constipation, risk assessment for falls, and patient monitoring for cognitive impairment.For patients with jobs that involve potentially hazardous tasks and who are receiving opioids or other medications that can negatively affect sleep, cognition, balance, or coordination, clinicians should assess patients’ abilities to safely perform the potentially hazardous tasks .Clinicians should use PDMP data (see Recommendation 9) and toxicology screening (see Recommendation 10) as appropriate to assess for concurrent substance use that might place patients at higher risk for opioid use disorder and overdose.Clinicians should provide specific counseling on increased risks for overdose when opioids are combined with other drugs or alcohol (see Recommendation 2) and ensure that patients are provided or receive effective treatment for substance use disorders when needed (see Recommendation 12).Although substance use disorders can alter the expected benefits and risks of opioid therapy for pain, patients with co-occurring pain and substance use disorder require ongoing pain management that maximizes benefits relative to risks. If clinicians consider opioid therapy for chronic pain for patients with substance use disorder, they should discuss increased risks for opioid use disorder and overdose with patients, carefully consider whether benefits of opioids outweigh increased risks, and incorporate strategies to mitigate risk into the management plan .If patients experience nonfatal opioid overdose, clinicians should evaluate for opioid use disorder and treat or arrange treatment if needed. Clinicians should work with patients to reduce opioid dosage and to discontinue opioids when indicated (see Recommendation 5) and should ensure continued close monitoring and support for patients prescribed or not prescribed opioids.If clinicians continue opioid therapy in patients with previous opioid overdose, they should discuss increased risks for overdose with patients, carefully consider whether benefits of opioids outweigh substantial risks, and incorporate strategies to mitigate risk into the management plan .The clinical evidence reviews found evidence too limited to determine effects of patient demographics and comorbidities on risk for opioid-related harms , and referral for treatment of pregnant persons with opioid use disorder improve both maternal and infant outcomes (The American Academy of Pediatrics (AAP) has published recommendations for the care of infants with neonatal opioid withdrawal syndrome, including that pregnant persons with opioid use disorder should receive antenatal counseling to provide education on the clinical signs of withdrawal and on postnatal treatment for neonatal opioid withdrawal syndrome   and opioid therapy in this population. Because of reduced renal function and medication clearance even in the absence of renal disease, patients aged ≥65 years might have increased susceptibility to accumulation of all medications, increased risk for drug-drug interactions, and a smaller therapeutic window between safe dosages and dosages associated with adverse effects. These adverse effects include renal, cardiovascular, and gastrointestinal effects with oral NSAIDs (see Recommendation 2) and respiratory depression and overdose with opioids. A case-control analysis among veterans prescribed opioids found that age ≥55 years was associated with increased risk for life-threatening respiratory/central nervous system depression or overdose  for patients aged ≥65 years to ensure pain is addressed and minimize risks of opioids prescribed. Clinicians should educate older adults receiving opioids to avoid medication-related behaviors that increase risk, such as saving unused medications. Caregivers can have an important role in management of opioid therapy for older persons with cognitive impairment. Clinicians also should implement interventions to mitigate common risks of opioid therapy among older adults, such as monitoring for cognitive impairment, risk assessment for falls, and exercise and bowel regimens to prevent constipation.A safety critical job involves work or an occupational environment where limitations in physical or mental performance, or both, involve dangers to self, coworkers, or the public. According to the American College Occupational Environmental Medicine, for occupations with higher risks , prescription of an opioid might be incompatible with continued employment in a safety critical job -7 and the Patient Health Questionnaire (PHQ-9 or PHQ-4) to support assessment for anxiety, posttraumatic stress disorder (PTSD), and depression   and increasing frequency of monitoring (see Recommendation 7) when opioids are prescribed. Clinicians should communicate with patients’ substance use disorder treatment providers if opioids are prescribed. Although substance use disorders can alter the expected benefits and risks of opioid therapy for pain, patients with co-occurring pain and substance use disorder require ongoing pain management that maximizes benefits relative to risks. Previous opioid overdose is associated with substantially increased risk for future nonfatal or fatal opioid overdose , patients at risk for returning to a high dose to which they have lost tolerance , and patients taking higher dosages of opioids (≥50 MME/day). Practices should provide education on overdose prevention and naloxone use to patients receiving naloxone prescriptions and members of their households. Naloxone coprescribing can be facilitated by clinics or practices with resources to provide naloxone training and by collaborative practice models with pharmacists. Resources for prescribing naloxone in primary care settings can be found through Prescribe to Prevent at When prescribing initial opioid therapy for acute, subacute, or chronic pain, and periodically during opioid therapy for chronic pain, 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 combinations that put the patient at high risk for overdose .Ideally, PDMP data should be reviewed before every opioid prescription for acute, subacute, or chronic pain. This practice is recommended in all jurisdictions where PDMP availability and access policies, as well as clinical practice settings, make it practicable .At a minimum, during long-term opioid therapy, PDMP data should be reviewed before an initial opioid prescription and then every 3 months or more frequently. Recommendation category B acknowledges variation in PDMP availability and circumstances. However, because PDMP information can be most helpful when results are unexpected and, to minimize bias in application, clinicians should apply this recommendation when feasible to all patients rather than differentially on the basis of assumptions about what they will learn about specific patients.Clinicians should use specific PDMP information about medications prescribed to their patient in the context of other clinical information, including their patient’s history, physical findings, and other relevant testing, to help them communicate with and protect their patient.Clinicians should review PDMP data specifically for prescription opioids and other controlled medications patients have received from additional prescribers to determine whether a patient is receiving total opioid dosages or combinations  that put the patient at risk for overdose.PDMP-generated risk scores have not been validated against clinical outcomes such as overdose and should not take the place of clinical judgment.Clinicians should not dismiss patients from their practice on the basis of PDMP information. Doing so can adversely affect patient safety and could result in missed opportunities to provide potentially lifesaving information  and interventions .Clinicians should take actions to improve patient safety:Discuss information from the PDMP with the patient and confirm that the patient is aware of any additional prescriptions. Because clinicians often work as part of teams, prescriptions might appropriately be written by more than one clinician coordinating the patient’s care. Occasionally, PDMP information can be incorrect .Discuss safety concerns, including increased risk for respiratory depression and overdose, with patients found to be receiving overlapping prescription opioids from multiple clinicians who are not coordinating the patient’s care or patients who are receiving medications that increase risk when combined with opioids  (see Recommendation 11), and offer naloxone (see Recommendation 8).Use particular caution when prescribing opioid pain medication and benzodiazepines concurrently, understanding that some patient circumstances warrant prescribing of these medications concomitantly. Clinicians should communicate with others managing the patient to discuss the patient’s needs, prioritize patient goals, weigh risks of concurrent benzodiazepine and opioid exposure, and coordinate care (see Recommendation 11).Consider the total MME/day for concurrent opioid prescriptions to help assess the patient’s overdose risk (see Recommendation 4). Buprenorphine should not be counted in the total MME/day in calculations because of its partial agonist properties at opioid receptors that confer a ceiling effect on respiratory depression. If a patient is found to be receiving total daily dosages of opioids that put them at risk for overdose, discuss safety concerns with the patient, consider in collaboration with the patient whether or not benefits of tapering outweigh risks of tapering (see Recommendation 5), and offer naloxone (see Recommendation 8).Discuss safety concerns with other clinicians who are prescribing controlled substances for the patient. Ideally, clinicians should first discuss concerns with the patient and inform them that they plan to coordinate care with their other clinicians to improve the patient’s safety.Screen for substance use and discuss concerns with the patient in a nonjudgmental manner (see Recommendations 8 and 12).When diverting (sharing or selling prescription opioids and not taking them) might be likely, consider toxicology testing to assist in determining whether prescription opioids can be discontinued without causing withdrawal (see Recommendations 5 and 10). A negative toxicology test for prescribed opioids might indicate the patient is not taking prescribed opioids, although clinicians should consider other possible reasons for this test result  (see Recommendation 10).PDMPs are databases overseen by states, territories, counties, and the District of Columbia that collect information on controlled prescription drugs dispensed by pharmacies and, in selected jurisdictions, by dispensing clinicians. PDMPs do not report nonprescribed opioid use. A clinical evidence review did not find studies evaluating the effectiveness of PDMPs for risk mitigation . At a minimum, PDMP data should be reviewed before initial opioid prescriptions for subacute or chronic pain and then every 3 months or more frequently during long-term opioid therapy. Recommendation category B acknowledges variation in PDMP availability and circumstances . However, because PDMP information can be most helpful when results are unexpected and, to minimize bias in application, clinicians should apply this recommendation when feasible to all patients rather than differentially on the basis of assumptions about what they will learn about specific patients.Clinicians should review PDMP data for prescription opioids and other controlled medications patients might have received from additional prescribers to determine the total amount of MME prescribed and to assess if the total dosage or combinations  put the patient at high risk for overdose. If patients are found to have total opioid dosages or combinations of medications that might put them at risk for overdose, or multiple controlled substance prescriptions written by different clinicians, clinicians should take actions to improve patient safety .When prescribing opioids for subacute or chronic pain, clinicians should consider the benefits and risks of toxicology testing to assess for prescribed medications as well as other prescribed and nonprescribed controlled substances .Toxicology testing should not be used in a punitive manner but should be used in the context of other clinical information to inform and improve patient care. Clinicians should not dismiss patients from care on the basis of a toxicology test result. Dismissal could have adverse consequences for patient safety, potentially including the patient obtaining opioids or other drugs from alternative sources and the clinician missing opportunities to facilitate treatment for substance use disorder.Before starting opioids and periodically  during opioid therapy, clinicians should consider the benefits and risks of toxicology testing to assess for prescribed opioids and other prescription and nonprescription controlled substances that increase risk for overdose when combined with opioids, including nonprescribed and illicit opioids and benzodiazepines.Clinicians, practices, and health systems should aim to minimize bias in testing and should not apply this recommendation differentially on the basis of assumptions about patients.Predicting risk is challenging, and available tools do not allow clinicians to reliably identify patients who are at low risk for substance use or substance use disorders. Clinicians should consider toxicology screening results as potentially useful data, in the context of other clinical information, for all patients and consider toxicology screening whenever its potential limitations can be addressed.Clinicians should explain to patients that toxicology testing will not be used to dismiss patients from care and is intended to improve their safety.Clinicians should explain expected results  and ask patients in a nonjudgmental manner about use of prescribed and other drugs and whether there might be unexpected results.Limited toxicology screening can be performed with a relatively inexpensive presumptive immunoassay panel that tests for opiates as a class, benzodiazepines as a class, and several nonprescribed substances. Toxicology screening for a class of drugs might not detect all drugs in that class. For example, fentanyl testing is not included in widely used toxicology assays that screen for opiates as a class.Clinicians should be familiar with the drugs included in toxicology screening panels used in their practice and should understand how to interpret results for these drugs. For example, a positive opiates immunoassay detects morphine, which might reflect patient use of morphine, codeine, or heroin, but does not detect synthetic opioids and might not detect semisynthetic opioids. In some cases, positive results for specific opioids might reflect metabolites from opioids the patient is taking and might not mean the patient is taking the specific opioid that resulted in the positive test.Confirmatory testing should be used whentoxicology results will inform decisions with major clinical or nonclinical implications for the patient;a need exists to detect specific opioids or other drugs within a class, such as those that are being prescribed, or those that cannot be identified on standard immunoassays; ora need exists to confirm unexpected screening toxicology test results.Restricting confirmatory testing to situations and substances for which results can reasonably be expected to affect patient management can reduce costs of toxicology testing.Clinicians might want to discuss unexpected results with the local laboratory or toxicologist and should discuss unexpected results with the patient.Clinicians should discuss unexpected results with patients in a nonjudgmental manner, avoiding use of potentially stigmatizing language .Discussion with patients before specific confirmatory testing can sometimes yield a candid explanation of why a particular substance is present or absent and remove the need for confirmatory testing during that visit. For example, a patient might explain that the test is negative for prescribed opioids because they felt opioids were no longer helping and discontinued them. If unexpected results from toxicology screening are not explained, a confirmatory test on the same sample using a method selective enough to differentiate specific opioids and metabolites  might be warranted.Clinicians should use unexpected results to improve patient safety .The clinical evidence reviews did not find studies evaluating the effectiveness of toxicology screening for risk mitigation during opioid prescribing for pain. However, concurrent use of opioid pain medications with other opioid pain medications, benzodiazepines, or heroin or other nonpharmaceutical opioids can increase patients’ risk for overdose. Toxicology tests can provide information about drug use that is not reported by the patient. In addition, toxicology tests can assist clinicians in identifying when patients are not taking opioids prescribed for them, which might in certain cases indicate diversion or other clinically important issues such as difficulties with adverse effects. The most commonly drug-tested bodily specimen is urine. Oral fluid  testing also is available  during opioid therapy, clinicians should consider benefits and risks of toxicology testing to assess for prescribed opioids and other prescription and nonprescribed substances that increase risk for overdose when combined with opioids, including nonprescribed and illicit opioids and benzodiazepines. Before ordering toxicology testing, clinicians should have a plan for responding to unexpected results. Clinicians should explain to patients that toxicology testing will not be used punitively  and is intended to improve their safety. Clinicians should also explain expected results . Clinicians should ask patients about use of prescribed medications and other substances and ask whether there might be unexpected results. This will provide an opportunity for patients to provide information about changes in their use of prescribed opioids or other drugs.In most situations, initial toxicology testing can be performed with a relatively inexpensive immunoassay panel that tests for opiates and benzodiazepines as classes and for multiple nonprescribed substances. Patients prescribed oxycodone or nonmorphine-based opioids  require specific testing for those agents. The use of confirmatory testing can add costs and should be used when toxicology results will inform decisions with major clinical or nonclinical implications for the patient, a need exists to detect a specific opioid that is prescribed or that cannot be identified on standard immunoassays, or to confirm unexpected toxicology screening results for which there is no other explanation. Clinicians and health systems can work to minimize inequitable cost burdens for patients and limit specific testing to situations when it is necessary. Clinicians should be familiar with the compounds included in toxicology testing panels used in their practice and should understand how to interpret results. For example, a positive opiate immunoassay test result detects morphine, which might reflect patient use of morphine, codeine, or heroin, but this immunoassay does not detect synthetic opioids  and might not detect semisynthetic opioids . Many laboratories use an oxycodone immunoassay that detects oxycodone and oxymorphone; however, these agents might need to be ordered or identified separately in a toxicology testing panel. In some cases, positive results for specific opioids might reflect metabolites from opioids the patient is taking and might not mean the patient is taking the specific opioid for which the test was positive. For example, hydromorphone is a metabolite of hydrocodone, and oxymorphone is a metabolite of oxycodone. Detailed considerations for interpretation of urine toxicology test results, including which tests to order and expected results, drug detection time in urine, and drug metabolism, have been published previously  might be warranted to clarify the situation.Clinicians should use unexpected results to improve patient safety . If tests for prescribed opioids are repeatedly negative, including confirmatory tests, and the clinician has verified that the patient is not taking the prescribed opioid, clinicians can discontinue the prescription without a taper and discuss options for safe disposal of unused opioids .Although in some circumstances it might be appropriate to prescribe opioids to a patient who is also prescribed benzodiazepines , clinicians should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently. In addition, clinicians should consider whether benefits outweigh risks for concurrent use of opioids with other central nervous system depressants .Buprenorphine or methadone for opioid use disorder should not be withheld from patients taking benzodiazepines or other medications that depress the central nervous system.Clinicians should check the PDMP for concurrent controlled medications prescribed by other clinicians (see Recommendation 9) and should consider involving pharmacists as part of the management team when opioids are coprescribed with other central nervous system depressants.In patients receiving opioids and benzodiazepines long term, clinicians should carefully weigh the benefits and risks of continuing therapy with opioids and benzodiazepines and discuss with patients and other members of the patient’s care team.Risks of concurrent opioid and benzodiazepine use are likely to be greater with unpredictable use of either medication, with use of higher-dosage opioids and higher-dosage benzodiazepines in combination, or with use with other substances including alcohol .In specific situations, benzodiazepines can be beneficial, and stopping benzodiazepines can be destabilizing.Clinicians should taper benzodiazepines gradually before discontinuation because abrupt withdrawal can be associated with rebound anxiety, hallucinations, seizures, delirium tremens, and, rarely, death. The rate of tapering should be individualized.If benzodiazepines prescribed for anxiety are tapered or discontinued, or if patients receiving opioids require treatment for anxiety, evidence-based psychotherapies , specific antidepressants or other nonbenzodiazepine medications approved for anxiety, or both, should be offered.Clinicians should communicate with other clinicians managing the patient to discuss the patient’s needs, prioritize patient goals, weigh risks of concurrent benzodiazepine and opioid exposure, and coordinate care.Benzodiazepines and opioids both cause central nervous system depression, and benzodiazepines can potentiate opioid-induced decreases in respiratory drive. Epidemiologic studies find concurrent benzodiazepine use in large proportions of opioid-related overdose deaths , clinicians should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently. In addition, because other central nervous system depressants   should be individualized and reevaluated over time. Considerations include patient priorities, the patient’s clinical considerations, the patient’s response to therapeutic changes, consultation with other clinicians managing the patient’s care, and, consultation with other specialists  if needed. Clinicians should taper benzodiazepines gradually before discontinuation because abrupt withdrawal can be associated with rebound anxiety, hallucinations, seizures, delirium tremens, and, rarely, death .Although stigma can reduce the willingness of persons with opioid use disorder to seek treatment, opioid use disorder is a chronic, treatable disease from which persons can recover and continue to lead healthy lives.If clinicians suspect opioid use disorder, they should discuss their concern with their patient in a nonjudgmental manner and provide an opportunity for the patient to disclose related concerns or problems.Clinicians should assess for the presence of opioid use disorder using DSM-5 criteria.For patients meeting criteria for opioid use disorder, particularly if moderate or severe, clinicians should offer or arrange for patients to receive evidence-based treatment with medications for opioid use disorder.Clinicians should not dismiss patients from their practice because of opioid use disorder because this can adversely affect patient safety.Medication treatment of opioid use disorder has been associated with reduced risk for overdose and overall deaths. Identification of opioid use disorder represents an opportunity for a clinician to initiate potentially life-saving interventions, and the clinician should collaborate with the patient regarding their safety to increase the likelihood of successful treatment.For pregnant persons with opioid use disorder, medication for opioid use disorder (buprenorphine or methadone) is the recommended therapy and should be offered as early as possible in pregnancy to prevent harms to both the patient and the fetus.Clinicians unable to provide treatment themselves should arrange for patients with opioid use disorder to receive care from a substance use disorder treatment specialist , or from an opioid treatment program certified by SAMHSA to provide methadone or buprenorphine for patients with opioid use disorder.All clinicians, and particularly clinicians prescribing opioids in communities without sufficient treatment capacity for opioid use disorder, should obtain a waiver to prescribe buprenorphine for opioid use disorder.Clinicians prescribing opioids should identify treatment resources for opioid use disorder in the community, establish a network of referral options that span the levels of care that patients might need to enable rapid collaboration and referral, when needed, and work together to ensure sufficient treatment capacity for opioid use disorder at the practice level.Although identification of an opioid use disorder can alter the expected benefits and risks of opioid therapy for pain, patients with co-occurring pain and opioid use disorder require ongoing pain management that maximizes benefits relative to risks.Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV])  are taken to relieve or avoid withdrawal symptoms.Criteria 10 and 11 are not considered to be met for those persons taking opioids solely under appropriate medical supervision , methadone (a full agonist opioid), and naltrexone (an opioid antagonist). Experts from OWG stated that partial agonist opioid, full agonist opioid, and opioid antagonist treatment should not be framed as equal options for opioid use disorder, noting that partial and full agonist opioid treatments have stronger evidence for better outcomes, do not require abstinence, have less challenges with initiation, and are much more widely used than opioid antagonist treatment. Clinical evidence reviews found evidence on the effectiveness of interventions  for opioid use disorder related to prescription opioids to be limited  or from toxicology testing (see Recommendation 10), they should discuss their concern with their patient and provide an opportunity for the patient to disclose related concerns or problems. Clinicians should assess for the presence of opioid use disorder using DSM-5 criteria  have been associated with improved maternal outcomes and should be offered as early as possible in pregnancy to prevent harms to both the patient and the fetus (see Recommendation 8)  methadone or buprenorphine to treat acute opioid withdrawal for up to 3 days, while working to refer the patient to opioid use disorder treatment  and SAMHSA’s Opioid Treatment Program Directory (https://dpt2.samhsa.gov/treatment/directory.aspx). Clinicians should assist patients in finding qualified treatment specialists, should arrange for patients to follow up with these specialists, and should coordinate continuing care with these specialists. Rapidly identifying appropriate care can be challenging. Treatment need in a community is often not met by capacity to provide buprenorphine or methadone therapy (https://pcssnow.org/) offers training, technical assistance, and mentors to assist clinicians in assessment for and treatment of substance use disorders, specifically opioid use disorder, and on the interface of pain and opioid misuse. Clinicians prescribing opioids should identify treatment resources for substance use disorders including opioid use disorders in the community, establish a network of referral options that span the levels of care that patients might need to enable rapid collaboration and referral, when needed, and work together to ensure sufficient treatment capacity at the practice level.Clinicians are strongly encouraged to provide medication treatment for their patients with opioid use disorder. Those unable to provide treatment themselves should arrange for patients with opioid use disorder to receive care from a colleague who is able to provide treatment, from a substance use disorder treatment specialist , or from an opioid treatment program certified by SAMHSA to provide methadone or buprenorphine for patients with opioid use disorder. Resources to help clinicians arrange for treatment include SAMHSA’s buprenorphine physician locator  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. In addition, five guiding principles were identified to inform implementation across recommendations. These guiding principles focus on 1) the appropriate treatment of pain; 2) flexibility to meet the care needs and clinical circumstances of each patient; 3) a multimodal and multidisciplinary approach to pain management; 4) avoiding misapplication of the clinical practice guideline beyond its intended use; and 5) vigilance in attending to health inequities and ensuring access to appropriate, affordable, diversified, coordinated, and effective nonpharmacologic and pharmacologic pain treatment for all persons.A central tenet of this clinical practice guideline is that acute, subacute, and chronic pain needs to be appropriately and effectively treated regardless of whether opioids are part of a treatment regimen. Clinicians should select nonpharmacologic or pharmacologic treatment modalities, or both, that maximize patient safety and optimize outcomes in pain, function, and quality of life. A multimodal and multidisciplinary approach to pain management that considers the biologic, psychological, and social characteristics of each person is critical  and decision support  can be used to facilitate and encourage evidence-based treatments as default treatments for pain  versus full agonist opioids for pain.Comparative effectiveness and risks of interventional procedures as part of a comprehensive pain management plan.Effects of therapies on nonpain outcomes.Treatment outcomes for specific pain conditions and how benefits and risks of therapies vary among subpopulations.Adapting evidence-based opioid prescribing and pain management strategies to meet the needs of special populations, including persons from some racial and ethnic groups, older adults, and persons living in rural communities.Effectiveness of clinician and health system strategies to promote equitable access to high-quality pain management.Improved diagnostics in measuring pain.Enhanced clinician and patient education about pain and the use of opioids, and the assessment of practice-level strategies in health systems to improve management and care coordination for patients on opioid therapy.Transition from acute to chronic pain and how to apply effective diagnostic, preventive, and therapeutic approaches.Effects of stigma as a barrier for treating pain and receiving treatment for an opioid use disorder, and effective ways to counter the effects of stigma on access to treatment for pain and opioid use disorder.The principal aim of this clinical practice guideline is to ensure persons have equitable access to safe and effective pain management that improves their function and quality of life while illuminating and reducing risks associated with prescription opioids. CDC will evaluate this clinical practice guideline to identify the effects of the recommendations on clinician and patient outcomes and on health disparities, including intended and unintended consequences. Communication between clinicians and patients about the benefits and risks of opioids should be central to treatment decisions for patients in pain. This clinical practice guideline can help inform those decisions and assist clinicians in meeting the unique needs of each person. CDC will revisit this clinical practice guideline when remaining evidence gaps have sufficiently been addressed and another update is warranted.