CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022

Recommendations

This clinical practice guideline includes 12 recommendations for clinicians who are prescribing opioids for outpatients aged ≥18 years with acute (duration of <1 month), 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 (Box 3). The recommendations are not intended to be implemented as absolute limits of policy or practice across populations by organizations, health care systems, or government entities. In accordance with the ACIP adapted GRADE method, CDC based the recommendations on consideration of clinical evidence, contextual evidence (e.g., benefits and harms, values and preferences, and resource allocation), and expert opinion. Expert input is reflected within the recommendation rationales. For each recommendation statement, CDC notes the recommendation category (A or B) and the type of evidence (1, 2, 3, or 4) supporting the statement (Box 3).

Category 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 (106,116) and GRADE method (103), category A recommendations were made, even with type 3 and 4 evidence, when there was broad agreement that the advantages of a clinical action greatly outweighed the disadvantages. Category B recommendations were made when there was broad agreement that the advantages and disadvantages of a clinical action were more balanced, but advantages were significant enough to warrant a recommendation. Recommendations were associated with a range of evidence types, from type 1 to type 4.

In summary, the categorization of recommendations was based on the following assessment:

A number of nonpharmacologic treatments and nonopioid medications are associated with improvements in pain, function, or both that are reportedly comparable to improvements associated with opioid use (7–11).
Evidence exists that multiple noninvasive nonpharmacologic interventions improve chronic pain and function, with small to moderate effects in specific pain conditions, and are not associated with serious harms. Compared with medication treatment, for which benefits are anticipated while patients are taking the medication but are not usually expected to persist after patients stop taking the medication, multiple noninvasive nonpharmacologic interventions are associated with improvements in pain, function, or both that are sustained after completion of treatment (9).
Nonopioid drugs, including serotonin and norepinephrine reuptake inhibitor (SNRI) 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 (8).
Opioid therapy is associated with similar or decreased effectiveness for pain and function versus NSAIDs across multiple common acute pain conditions (10). Opioid therapy is associated with small improvements in short-term (duration of 1 to <6 months) pain and function compared with placebo, with increased short-term harms compared with placebo, and with evidence of attenuated pain reduction over time (between 3 and 6 months versus between 1 and 3 months) (10). Evidence exists from observational studies of an association between opioid use for acute pain and long-term opioid use (10). Evidence on long-term effectiveness of opioids remains very limited (7); a long-term (12 months) randomized trial of stepped therapy for chronic musculoskeletal pain found no difference in function and higher pain intensity after starting with opioid therapy compared with starting with nonopioid therapy (74). Evidence exists of increased risk for serious harms (including opioid use disorder and overdose) with long-term opioid therapy that appears to rise with increase in opioid dosage, without a clear threshold below which there is no risk (7).
No validated, reliable way exists to predict which patients will experience serious harm from opioid therapy and which patients will benefit from opioid therapy (7).
Discontinuing opioids after extended periods of continuous opioid use can be challenging for clinicians and patients. Tapering or discontinuing opioids in patients who have taken them long term can be associated with clinically significant risks (68), particularly if opioids are tapered rapidly or patients do not receive effective support.
Patients, caregivers, and clinicians responded to CDC with invited input about their experiences and perspectives related to pain and pain management options. Themes included strained patient-clinician relationships and the need for patients and clinicians to make shared decisions, the effects of misapplication of the 2016 CDC Opioid Prescribing Guideline, inconsistent access to effective pain management solutions, and achieving reduced prescription opioid use through diverse approaches.
Members of the public responded to CDC with invited comments. Themes included experiences with pain or experiences in the aftermath of the overdose of a friend, family member, or significant other; barriers and access to pain care and to evidence-based treatment; concerns about the level of specificity of recommendations; and overall communication and implementation of the clinical practice guideline.

Each of the 12 recommendation statements is followed by considerations for implementation and a rationale for the recommendation. The implementation considerations offer practical insights, context, and specific examples meant to further inform clinician-patient decision-making for the respective recommendation and are not meant to be rigidly or inflexibly followed.

The recommendations are grouped into four areas:

Determining whether or not to initiate opioids for pain
Selecting opioids and determining dosages
Deciding duration of initial opioid prescription and conducting follow-up
Assessing risk and addressing potential harms of opioid use

In addition, these five guiding principles should broadly inform implementation across recommendations (Box 4):

Acute, subacute, and chronic pain needs to be appropriately assessed and treated independent of whether opioids are part of a treatment regimen.
Recommendations are voluntary and are intended to support, not supplant, individualized, person-centered care. Flexibility to meet the care needs and the clinical circumstances of a specific patient is paramount.
A multimodal and multidisciplinary approach to pain management attending to the physical health, behavioral health, long-term services and supports, and expected health outcomes and well-being of each person is critical.
Special attention should be given to avoid misapplying this clinical practice guideline beyond its intended use or implementing policies purportedly derived from it that might lead to unintended and potentially harmful consequences for patients.
Clinicians, practices, health systems, and payers should vigilantly attend to health inequities; provide culturally and linguistically appropriate communication (117), including communication that is accessible to persons with disabilities; and ensure access to an appropriate, affordable, diversified, coordinated, and effective nonpharmacologic and pharmacologic pain management regimen for all persons.

Determining Whether or Not to Initiate Opioids for Pain

All patients with pain should receive treatment that provides the greatest benefits relative to risks. (See Recommendation 1 for determining whether or not to initiate opioids for acute pain [i.e., pain lasting <1 month] and Recommendation 2 for determining whether or not to initiate opioids for subacute pain [i.e., pain lasting 1–3 months] or chronic pain [i.e., pain lasting >3 months].)

Recommendation 1

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 (recommendation category: B; evidence type: 3).

Implementation Considerations

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 (e.g., sprains, strains, tendonitis, and bursitis), pain related to minor surgeries typically associated with minimal tissue injury and mild postoperative pain (e.g., simple dental extraction), dental pain, kidney stone pain, and headaches including episodic migraine.
Clinicians should maximize use of nonopioid pharmacologic (e.g., topical or oral NSAIDs, acetaminophen) and nonpharmacologic (e.g., ice, heat, elevation, rest, immobilization, or exercise) 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 (e.g., hydrocodone 5 mg/acetaminophen 325 mg, one tablet not more frequently than every 4 hours as needed for moderate to severe pain) rather than on a scheduled basis (e.g., one tablet every 4 hours) 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 (e.g., for superimposed severe acute pain), 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.

Supporting Rationale

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 (e.g., surgical intervention to repair structure and function after certain traumatic injuries, bracing to prevent recurrence of acute ankle sprain, fracture immobilization, ice or elevation to reduce swelling, and early mobilization to maintain function) (118).

Noninvasive Nonpharmacologic Approaches to Acute Pain

Noninvasive nonpharmacologic approaches to acute pain have the potential to improve pain and function without risk for serious harms (10). Clinical evidence reviews found that some nonpharmacologic treatments were likely effective for acute pain, such as heat therapy for acute low back pain; several others might be effective for specific acute pain conditions, such as spinal manipulation for acute back pain with radiculopathy, a cervical collar or exercise for acute neck pain with radiculopathy, acupressure for acute musculoskeletal pain, massage for postoperative pain (10), and remote electrical neuromodulation for acute pain related to episodic migraine (11).

The American College of Physicians (ACP) recommends nonpharmacologic treatment with superficial heat, massage, acupuncture, or spinal manipulation as a cornerstone of treatment for acute low back pain (119). ACP and the American Academy of Family Physicians (AAFP) suggest acupressure to improve pain and function and transcutaneous electrical nerve stimulation to reduce pain in patients with acute musculoskeletal injuries (120).

Despite evidence supporting their use, noninvasive nonpharmacologic therapies are not always or fully covered by insurance (43), and access and cost can be barriers, particularly for persons who are uninsured, have limited income, have transportation challenges, or live in rural areas where treatments are not available (121). Experts from OWG expressed concern about limited access to nonopioid pain management modalities, in part because of lack of availability or lack of coverage by payers, and emphasized improving access to nonopioid pain management modalities as a priority. Health insurers and health systems can contribute to improved pain management and reduced medication use by increasing access to noninvasive nonpharmacologic therapies with evidence of effectiveness (9,43). Noninvasive nonpharmacologic approaches should be used as appropriate to alleviate acute pain, including ice and elevation to reduce swelling and discomfort from musculoskeletal injuries, heat to alleviate low back pain, and other modalities depending on the cause of the acute pain.

Nonopioid Medications for Acute Pain

Many acute pain conditions often can be managed most effectively with nonopioid medications (10,122). A systematic review found that for musculoskeletal injuries such as sprains, whiplash, and muscle strains, topical NSAIDs provided the greatest benefit-harm ratio, followed by oral NSAIDs or acetaminophen with or without diclofenac (122). NSAIDs have been found to be more effective than opioids for surgical dental pain and kidney stone pain and similarly effective to opioids for low back pain (10). Evidence is limited on comparative effectiveness of therapies for acute neuropathic pain, neck pain, and postoperative pain (10). For episodic migraine, triptans, NSAIDs, antiemetics, dihydroergotamine, calcitonin gene-related peptide antagonists (gepants), and lasmiditan are associated with improved pain and function with usually mild and transient adverse events (11).

ACP recommends NSAIDs or skeletal muscle relaxants if pharmacologic treatment is desired to treat low back pain (119). For acute musculoskeletal injuries other than low back pain, ACP and AAFP recommend topical NSAIDs with or without menthol gel as first-line therapy and suggest oral NSAIDs to relieve pain or improve function or oral acetaminophen to reduce pain (120). The American Dental Association (ADA) recommends NSAIDs as first-line treatment for acute dental pain management (123). For acute kidney stone pain, NSAIDs are at least as effective as opioids (124–127), can decrease the ureteral smooth muscle tone and ureteral spasm (128) causing kidney stone pain, and are preferred for kidney stone pain if not contraindicated. Triptans, NSAIDs, combined triptans with NSAIDs, antiemetics, dihydroergotamine, and acetaminophen are established acute treatments for migraine (11). Lasmiditan, an 5-HT1F receptor agonist, and ubrogepant, a gepant, were approved by FDA in 2019 for the treatment of migraine (129); another gepant, rimegepant, was approved in 2020. Lasmiditan and the gepants were more effective than placebo in providing pain relief at 2 hours, 1 day, and 1 week (11). Adverse events related to these newer medications require further study; however, their mechanisms of action are believed to be nonvasoconstrictive (130) and potentially carry lower risks than vasoactive medications in patients with cardiovascular risk factors (11).

When not contraindicated, NSAIDs should be used for low back pain, painful musculoskeletal injuries (including minor pain related to fractures), 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 (8), particularly in patients with cardiovascular or gastrointestinal comorbidities, and clinicians should weigh risks and benefits of use, dose, and duration of NSAIDs when treating older adults as well as patients with hypertension, renal insufficiency, heart failure, or those with risk for peptic ulcer disease or cardiovascular disease. Vasoactive effects of triptans and ergot alkaloids might preclude their use in patients with migraine who also have cardiovascular risk factors (11,131,132). Clinicians should review FDA-approved labeling, including boxed warnings, before initiating treatment with any pharmacologic therapy.

Pain Management for Pregnant and Postpartum Persons

For pain management in the postpartum period, the American College of Obstetricians and Gynecologists (ACOG) 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 (133). ACOG recommends counseling persons who are prescribed opioids about the risk for central nervous system depression in the postpartum person and in the breastfed infant (133), noting that if a codeine-containing medication is selected, duration of therapy and neonatal signs of toxicity should be reviewed with patients and their families (133).

Opioid Medication for Acute Pain

A systematic review found that for musculoskeletal injuries such as sprains, whiplash, and muscle strains, no opioid provided better benefit than NSAIDs, and opioid use caused the most harms (122). The evidence review (10) found that opioids might not be more effective than nonopioid therapies for some acute pain conditions (134–138), and use of opioids might negatively affect recovery and function (139,140). The review found that opioids were probably less effective than NSAIDs for surgical dental pain and kidney stone pain, less effective than acetaminophen for kidney stone pain, and similarly effective as NSAIDs for low back pain (10). For postoperative pain, effects of opioids on pain intensity were inconsistent, and opioids were associated with increased likelihood of repeat or rescue analgesic use (10). Evidence was insufficient for opioids in treatment of episodic migraine (11). Compared with NSAIDs or acetaminophen, opioids were associated with increased risk for short-term adverse events, including any adverse event, nausea, dizziness, and somnolence (10). Observational studies found that opioid use for acute low back pain or postoperative pain was associated with increased likelihood of long-term opioid use (10). Proportions of adults with new long-term opioid use at follow-up after initiation for short-term use for postoperative pain have ranged from <1% to 13% (141–146). Odds of long-term opioid use at follow-up after initiation for short-term use for acute pain might be greater with higher dosage and longer initial duration of exposure. For example, one study found that, compared with no early opioid use for acute low back pain, the adjusted odds ratio was 2.08 (95% CI: 1.55–2.78) for an early prescription totaling 1–140 MME and increased to 6.14 (95% CI: 4.92–7.66) for an early prescription totaling ≥450 MME (140). In episodic migraine, opioids as well as butalbital-containing medications were associated with a twofold higher risk for development of medication overuse headache compared with simple analgesics and triptans (11,147). Serious adverse events were uncommon for opioids and other medications; however, studies were not designed to assess risk for overdose, opioid use disorder, or long-term harms (10).

For acute low back pain, ACP found insufficient evidence for effectiveness of opioids and recommends nonopioid medications (see Nonopioid Medications for Acute Pain) if choosing pharmacologic treatment (119). ACP and AAFP suggest against treating patients with acute pain from musculoskeletal injuries with opioids, including tramadol (120). ADA recommends NSAIDs as the first-line therapy for acute pain management (see Nonopioid Medications for Acute Pain) (123). Multiple guidelines that address prescribing for postoperative pain include both nonopioid and opioid treatment options and have emphasized multimodal analgesia, incorporating around-the-clock nonopioid analgesics and nonpharmacologic therapies and noting that systemic opioids often are needed postoperatively but are not required in all patients (148–151). The American Headache Society recommends against prescribing opioid or butalbital-containing medications as first-line treatment for recurrent headache disorders (152), and the American Academy of Neurology also recommends against use of both of these classes of medications for treatment of migraine, except as a last resort (153).

Because of equivalent or lesser effectiveness for pain relief compared with NSAIDs and risks for long-term opioid use after using opioids for acute pain, opioids are not recommended as first-line therapy for many common acute pain conditions, including low back pain, neck pain, pain related to other musculoskeletal injuries (e.g., sprains, strains, tendonitis, and bursitis), pain related to minor surgeries typically associated with minimal tissue injury and only mild postoperative pain (e.g., simple dental extraction), 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 (e.g., NSAIDs, acetaminophen, or both) and nonpharmacologic (e.g., ice, heat, elevation, rest, immobilization, or exercise) 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 (e.g., hydrocodone 5 mg/acetaminophen 325 mg, one tablet not more frequently than every 4 hours as needed for moderate to severe pain) rather than on a scheduled basis (e.g., one tablet every 4 hours), 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 (see Recommendation 12 and the ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update) (96).

Although findings regarding risks for new long-term opioid use after use for acute pain (10) relate specifically to patients who were previously opioid naïve, risks also might be associated with dosage escalation (see Recommendation 4) if patients already treated with long-term opioids are prescribed additional opioid medication for new acute pain superimposed on chronic pain. Therefore, strategies that minimize opioid use should be implemented for both opioid-naïve and opioid-tolerant patients with acute pain when possible. If patients receiving long-term opioid therapy require additional medication for acute pain, nonopioid medications should be used when possible. If additional opioids are required (e.g., for superimposed severe acute pain), 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 an appropriate taper to baseline dosage if additional opioids were used around the clock for more than a few days (see Recommendation 6).

Patient education and discussion before starting outpatient opioid therapy are critical so that patient preferences and values can be understood and used to inform clinical decisions. 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. Essential elements for communication and discussion with patients before prescribing outpatient opioid therapy for acute pain include the following:

Advise patients that short-term opioid use can lead to unintended long-term opioid use and of the importance of working toward planned discontinuation of opioid use as soon as feasible, including a plan to appropriately taper opioids as pain resolves if opioids have been used around the clock for more than a few days (see Recommendation 6).
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 (e.g., a stimulant laxative such as senna, with or without a stool softener) 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 (e.g., taking the opioid only when needed if needed less frequently than every 4 hours and the prescription is written for every 4 hours as needed for 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 (e.g., 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 (i.e., not taking more opioids than prescribed or taking them more often).
Review increased risks for respiratory depression when opioids are taken with benzodiazepines, other sedatives, alcohol, nonprescribed or illicit drugs (e.g., heroin), 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 (154), and the value of having naloxone available.
Discuss planned use of precautions to reduce risks, including naloxone for overdose reversal (see Recommendation 8) and clinician use of PDMP information (see Recommendation 9).

Recommendation 2

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 (recommendation category: A; evidence type: 2).

Implementation Considerations

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 (e.g., aerobic, aquatic, or resistance exercises) or exercise therapy (a prominent modality in physical 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 (e.g., yoga, tai chi, or qigong), 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 (e.g., knee). 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 (e.g., pregabalin, gabapentin enacarbil, oxcarbazepine); 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 (e.g., amitriptyline) and SNRI antidepressants (e.g., duloxetine, milnacipran), NSAIDs (e.g., topical diclofenac), and specific anticonvulsants (i.e., pregabalin and gabapentin) 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 (e.g., serious illness in a patient with poor prognosis for return to previous level of function, contraindications to other therapies, and clinician and patient agreement that the overriding goal is patient comfort), opioids might be appropriate regardless of previous therapies used. In other situations (e.g., headache or fibromyalgia), 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.

Supporting Rationale

To guide patient-specific selection of therapy, clinicians should evaluate patients and establish or confirm the diagnosis (155). Detailed recommendations on diagnosis are provided in other guidelines (156–159). Evaluation should include a focused history, including history and characteristics of pain and potential contributing factors (e.g., function, work history and current work demands, psychosocial stressors, and sleep), and physical examination, with imaging or other diagnostic testing only if indicated (e.g., if severe or progressive neurologic deficits are present or if serious underlying conditions are suspected) (158,159). For complex pain syndromes, consultation with a pain specialist can be considered to assist with diagnosis and management.

Diagnosis can help identify disease-specific interventions to reverse, ameliorate, or prevent worsening of pain and improve function (e.g., improving glucose control to prevent progression of diabetic neuropathy; immune-modulating agents for rheumatoid arthritis; physical or occupational therapy to address posture, muscle weakness, or repetitive occupational motions that contribute to musculoskeletal pain; or surgical intervention to relieve severe mechanical or compressive pain) (159). The underlying mechanism for most pain syndromes has traditionally been categorized as neuropathic (e.g., diabetic neuropathy and postherpetic neuralgia) or nociceptive (e.g., osteoarthritis and muscular back pain). More recently, nociplastic pain has been suggested as a third, distinct category of pain with augmented central nervous system pain and sensory processing and altered pain modulation as experienced in conditions such as fibromyalgia (160). The diagnosis and pathophysiologic mechanism of pain have implications for symptomatic pain treatment with medication. For example, evidence is limited for improved pain or function, or evidence exists of worse outcomes, with long-term use of opioids for several chronic pain conditions for which opioids are commonly prescribed, such as osteoarthritis (161), nonspecific low back pain (119,162), headache (152), and fibromyalgia (163,164). For moderate to severe chronic back pain or hip or knee osteoarthritis pain, a nonopioid strategy starting with acetaminophen or NSAIDs results in improved pain intensity with fewer side effects compared with a strategy starting with opioids (74). Tricyclic antidepressants, SNRI antidepressants, selected anticonvulsants, or transdermal lidocaine are recommended for neuropathic pain syndromes (e.g., diabetic neuropathy or postherpetic neuralgia) (156).

Review of the patient's history and context beyond the presenting pain syndrome is helpful in selection of pain treatments. In particular, medications should be used only after assessment and determination that expected benefits outweigh risks, considering patient-specific factors. For example, clinicians should consider fall risk when selecting and dosing potentially sedating medications (e.g., tricyclic antidepressants, anticonvulsants, and opioids) 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 (165). Some guidelines recommend topical NSAIDs for localized osteoarthritis (e.g., knee osteoarthritis) over oral NSAIDs in patients aged ≥75 years to minimize systemic effects (166). (See Recommendation 8 for additional considerations for assessing risks of opioid therapy.)

Noninvasive Nonpharmacologic Approaches to Subacute and Chronic Pain

Many noninvasive nonpharmacologic approaches, including physical therapy, weight loss for knee osteoarthritis, and behavioral therapies (e.g., cognitive behavioral therapy and mindfulness-based stress reduction), can improve pain and function without risk for serious harms (9). High-quality evidence exists that exercise therapy (a prominent modality in physical therapy) for back pain, fibromyalgia, and hip or knee osteoarthritis reduces pain and improves function immediately after treatment and that the improvements are sustained for at least 2–6 months (9,167–170). Previous guidelines have recommended aerobic, aquatic, or resistance exercises for persons with chronic pain, including osteoarthritis of the knee or hip, back pain, and fibromyalgia (119,156,166,171). Other noninvasive nonpharmacologic therapies that improve pain, function, or both for at least 1 month after delivery without apparent risk for serious harm include cognitive behavioral therapy 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 (e.g., yoga, tai chi, and qigong), 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 (9). For temporomandibular disorder pain, patient education and self-care can be effective, as can occlusal splints for some patients and biobehavioral therapy for prevention of disabling symptoms (172,173). Exercise, mind-body interventions, and behavioral treatments (including cognitive behavioral therapy and mindfulness practices) can encourage active patient participation in the care plan and help address the effects of pain in the patient's life; these active therapies have somewhat more robust evidence for sustained improvements in pain and function than more passive treatments (e.g., massage), particularly at longer-term follow-up (9). In addition, physical activity can provide additional health benefits, such as preventing or reducing symptoms of depression (174). Active approaches that engage the patient should be used when possible, with a supplementary role for more passive approaches, to reduce pain and improve function.

Despite their favorable benefit-to-risk profile, noninvasive nonpharmacologic therapies are not always covered or fully covered by insurance (43). Access and cost can be barriers for patients, particularly persons who have low incomes, do not have health insurance or have inadequate insurance, have transportation challenges, or live in rural areas where services might not be available (121). 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 (9,43). In addition, for many patients, aspects of these approaches can be used even when access to specialty care is limited. For example, previous guidelines have strongly recommended aerobic, aquatic, or resistance exercises for patients with osteoarthritis of the knee or hip (166) and maintenance of physical activity, including normal daily activities, for patients with low back pain (158). A randomized trial found no difference in reduced chronic low back pain intensity, frequency, or disability between patients assigned to relatively low-cost group aerobics and those assigned to individual physiotherapy or muscle reconditioning sessions (175). 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. A randomized trial found a stepped exercise program, in which patients were initially offered an Internet-based exercise program and progressively advanced to biweekly coaching calls and then to in-person physical therapy if not improved at previous steps, successfully improved symptomatic knee osteoarthritis, with 35% of patients ultimately requiring in-person physical therapy (176). In addition, primary care clinicians can integrate elements of psychosocial therapies such as cognitive behavioral therapy, which addresses psychosocial contributors to pain and improves function (177), by encouraging patients to take an active role in the care plan, supporting patients in engaging in activities such as exercise that are typically beneficial but that might initially be associated with fear of exacerbating pain (159), or providing education in relaxation techniques and coping strategies. In many locations, free or low-cost patient support, self-help, and educational community-based or employer-sponsored programs are available that can provide stress reduction and other mental health benefits. Clinicians should become familiar with such options within their communities so they can refer patients to low-cost services. Patients with higher levels of anxiety or fear related to pain or other clinically significant psychological distress can be referred for treatment with a mental health specialist (e.g., psychologist, psychiatrist, or clinical social worker).

Nonopioid Medications for Subacute and Chronic Pain

Several nonopioid pharmacologic therapies (including acetaminophen, NSAIDs, and selected antidepressants and anticonvulsants) are used for painful symptoms in chronic pain conditions. Nonopioid pharmacologic therapies are associated with risks, particularly in older adults, pregnant patients, and patient...

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