Guidelines

Guideline for Prescribing Opioids

 

Determining When to Initiate or Continue Opioids for Chronic Pain

 

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

 

Patients with pain should receive treatment that provides the greatest benefits relative to risks.  Many nonpharmacologic therapies, including physical therapy, weight loss for knee osteoarthritis, psychological therapies such as Cognitive Behavior Therapy (CBT), and certain interventional procedures can ameliorate chronic pain.  Exercise therapy (a prominent modality in physical therapy) for hip or knee osteoarthritis reduces pain and improves function immediately after treatment and the improvements are sustained.  Previous guidelines have strongly recommended aerobic, aquatic, and/or resistance exercises for patients with osteoarthritis of the knee or hip.  Exercise therapy also can help reduce pain and improve function in low back pain and can improve global well-being and physical function in fibromyalgia.  Interventional approaches such as arthrocentesis and intraarticular glucocorticoid injection for pain associated with rheumatoid arthritis or osteoarthritis and subacromial corticosteroid injection for rotator cuff disease can provide short-term improvement in pain and function. 

 

Several nonopioid pharmacologic therapies (including acetaminophen, NSAIDs, and selected antidepressants and anticonvulsants) are effective for chronic pain.  In particular, acetaminophen and NSAIDs can be useful for arthritis and low back pain.  Selected anticonvulsants such as pregabalin (Lyrica) and gabapentin can improve pain in diabetic neuropathy and post-herpetic neuralgia.  Pregabalin, gabapentin, and carbamazepine (Tegretol) are approved for treatment of certain neuropathic pain conditions, and pregabalin is approved for fibromyalgia management.  In patients with or without depression, tricyclic antidepressants and SNRIs provide effective analgesia for neuropathic pain conditions including diabetic neuropathy and post-herpetic neuralgia, often at lower dosages and with a shorter time to onset of effect than for treatment of depression.  Tricyclics and SNRIs can also relieve fibromyalgia symptoms.  The SNRI duloxetine (Cymbalta) is approved for the treatment of diabetic neuropathy and fibromyalgia. 

 

Because patients with chronic pain often suffer from concurrent depression, and depression can exacerbate physical symptoms including pain, patients with co-occurring pain and depression are especially likely to benefit from antidepressant medication.  Nonopioid pharmacologic therapies are not generally associated with substance use disorder, and the numbers of fatal overdoses associated with nonopioid medications are a fraction of those associated with opioid medications.  However, nonopioid pharmacologic therapies are associated with certain risks, particularly in older patients, pregnant patients, and patients with certain co-morbidities such as cardiovascular, renal, gastrointestinal, and liver disease.

 

Although opioids can reduce pain during short-term use, there is insufficient evidence to determine whether pain relief is sustained and whether function or quality of life improves with long-term opioid therapy.  Long-term opioid use for chronic pain is associated with serious risks including increased risk for opioid use disorder, overdose, myocardial infarction, and motor vehicle injury.    

 

Integrated pain management requires coordination of medical, psychological, and social aspects of health care and includes primary care, mental health care, and specialist services when needed.  Low-cost options to integrate exercise include brisk walking in public spaces or use of public recreation facilities for group exercise.  CBT addresses psychosocial contributors to pain and improves function.  Primary care clinicians can integrate elements of a cognitive behavioral approach into their practice by encouraging patients to take an active role in the care plan, by supporting patients in engaging in beneficial but potentially anxiety-provoking activities, such as exercise, or by providing education in relaxation techniques and coping strategies.

 

Diagnosis can help identify disease-specific interventions to reverse or ameliorate pain; for example, 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 mechanical/compression pain.

 

Opioids should not be considered first-line or routine therapy for chronic pain (i.e., pain continuing or expected to continue >3 months or more past the time of normal tissue healing) outside of active cancer, palliative, and end-of-life care.  This does not mean that patients should be required to sequentially “fail” nonpharmacologic and nonopioid pharmacologic therapy before proceeding to opioid therapy.  Rather, expected benefits specific to the clinical context should be weighed against risks before initiating therapy.  In addition, when opioid pain medication is used, it is more likely to be effective if integrated with nonpharmacologic therapy. 


 

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

 

Studies of opioid therapy for chronic pain have found that although many patients discontinue opioid therapy for chronic noncancer pain due to adverse effects or insufficient pain relief, there is weak evidence that patients who are able to continue opioid therapy for at least 6 months can experience clinically significant pain relief and insufficient evidence that function or quality of life improves.  These findings suggest that it is very difficult for clinicians to predict whether benefits of opioids for chronic pain will outweigh risks of ongoing treatment for individual patients.  Opioid therapy should not be initiated without consideration of an “exit strategy” to be used if the therapy is unsuccessful.

 

Before opioid therapy is initiated for chronic pain outside of active cancer, palliative, and end-of-life care, clinicians should determine how effectiveness will be evaluated and should establish treatment goals with patients.  Clinicians seeing new patients already receiving opioids should establish treatment goals for continued opioid therapy.  Clinicians and patients who set a plan in advance will clarify expectations regarding how opioids will be prescribed and monitored, as well as situations in which opioids will be discontinued or doses tapered (e.g., if treatment goals are not met, opioids are no longer needed, or adverse events put the patient at risk) to improve patient safety.

 

Goals should include improvement in both pain relief and function (and therefore in quality of life).  Clinicians may use validated instruments such as the three-item “Pain average, interference with Enjoyment of life, and interference with General activity” (PEG) Assessment Scale to track patient outcomes.  Clinically meaningful improvement has been defined as a 30% improvement in scores for both pain and function.  Monitoring progress toward patient-centered functional goals (e.g., walking the dog or walking around the block, returning to part-time work, attending family sports or recreational activities) can also contribute to the assessment of functional improvement.  Because depression, anxiety, and other psychological co-morbidities often coexist with and can interfere with resolution of pain, clinicians should use validated instruments to assess for these conditions and ensure that treatment for these conditions is optimized.  If patients receiving opioid therapy for chronic pain do not experience meaningful improvements in both pain and function compared with prior to initiation of opioid therapy, clinicians should consider working with patients to taper and discontinue opioids and should use nonpharmacologic and nonopioid pharmacologic approaches to pain management.

PEG: A Three-Item Scale Assessing Pain Intensity and Interference with Enjoyment of Life and General Activity

1.What number best describes your pain on average in the past week?

     0        1       2       3       4       5       6       7       8       9       10

No pain                                                                              Pain as bad as you can imagine

2.  What number best describes how, during the past week, pain has interfered with your enjoyment of life?

     0        1       2       3       4       5       6       7       8       9       10

No pain                                                                              Pain as bad as you can imagine

3.  What number best describes how, during the past week, pain has interfered with your general activity?

     0        1       2       3       4       5       6       7       8       9       10

No pain                                                                              Pain as bad as you can imagine

 

3.  Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy.

 

Many patients lack information about opioids and some clinicians miss opportunities to effectively communicate about safety.  Essential elements to communicate to patients before starting and periodically during opioid therapy include realistic expected benefits, common and serious harms, and expectations for clinician and patient responsibilities to mitigate risks of opioid therapy.

 

Clinicians should involve patients in decisions about whether to start or continue opioid therapy.  Given potentially serious risks of long-term opioid therapy, clinicians should ensure that patients are aware of potential benefits of, harms of, and alternatives to opioids before starting or continuing opioid therapy.  Clinicians are encouraged to have open and honest discussions with patients to inform mutual decisions about whether to start or continue opioid therapy. 

 

Important considerations include the following: 

 

 

 

 

 

Given the possibility that benefits of opioid therapy might diminish or that risks might become more prominent over time, it is important that clinicians review expected benefits and risks of continued opioid therapy with patients periodically, at least every 3 months.

  

Opioid Selection, Dosage, Duration, Follow-Up, and Discontinuation

 

4.  When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids.

 

ER/LA opioids include methadone, transdermal fentanyl, and extended-release versions of opioids such as oxycodone (OxyContin), oxymorphone, hydrocodone, and morphine.  There is a higher risk for overdose among patients initiating treatment with ER/LA opioids than among those initiating treatment with immediate-release opioids.  There is no evidence that continuous, time-scheduled use of ER/LA opioids is more effective or safer than intermittent use of immediate-release opioids or that time-scheduled use of ER/LA opioids reduces risks for opioid misuse or addiction.

 

ER/LA opioids should be reserved for “management of pain severe enough to require daily, around-the-clock, long-term opioid treatment” when “alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain” and not used as “as needed” pain relievers.  Some ER/LA opioids are only appropriate for opioid-tolerant patients, defined as patients who have received certain dosages of opioids (e.g., 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids) for at least 1 week.  Time-scheduled opioid use can be associated with greater total average daily opioid dosage compared with intermittent, as-needed opioid use.  There is not enough evidence to determine the safety of using immediate-release opioids for breakthrough pain when ER/LA opioids are used for chronic pain outside of active cancer pain, palliative care, or end-of-life care, and that this practice might be associated with dose escalation.

 

Although abuse-deterrent technologies are expected to make manipulation of opioids more difficult or less rewarding, they do not prevent opioid abuse through oral intake, the most common route of opioid abuse, and can still be abused by nonoral routes.  The “abuse-deterrent” label does not indicate that there is no risk for abuse. 

 

For patients not already receiving opioids, clinicians should not initiate opioid treatment with ER/LA opioids and should not prescribe ER/LA opioids for intermittent use.  ER/LA opioids should be reserved for severe, continuous pain and should be considered only for patients who have received immediate-release opioids daily for at least 1 week. 

 

When an ER/LA opioid is prescribed, using one with predictable pharmacokinetics and pharmacodynamics is preferred to minimize unintentional overdose risk.  In particular, unusual characteristics of methadone and of transdermal fentanyl make safe prescribing of these medications for pain especially challenging.

 

 

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

Morphine milligram equivalent (MME) doses for commonly prescribed opioids

Opioid                                        Conversion factor

Codeine                                                         0.15

Fentanyl transdermal (in mcg/hr)              2.4

Hydrocodone                                               1

Hydromorphone                                          4

Methadone            

  1–20 mg/day                                               4

  21–40 mg/day                                             8

  41–60 mg/day                                             10

  ≥61–80 mg/day                                         12

Morphine                                                      1

Oxycodone                                                    1.5

Oxymorphone                                               3

 

Benefits of high-dose opioids for chronic pain are not established.  A randomized trial found no difference in pain or function between a more liberal opioid dose escalation strategy and maintenance of current dosage.  At the same time, risks for serious harms related to opioid therapy increase at higher opioid dosage. 

 

Although there is not a single dosage threshold below which overdose risk is eliminated, holding dosages <50 MME/day would likely reduce risk among a large proportion of patients who would experience fatal overdose at higher prescribed dosages.

 

When opioids are used for chronic pain outside of active cancer, palliative, and end-of-life care, clinicians should start opioids at the lowest possible effective dosage, with special caution for patients over 65 and those with impaired renal and hepatic function.  Clinicians should use caution when increasing opioid dosages and increase dosage by the smallest practical amount.  Clinicians should re-evaluate patients after increasing dosage for changes in pain, function, and risk for harm.  Before increasing total opioid dosage to ≥50 MME/day, clinicians should reassess whether opioid treatment is meeting the patient’s treatment goals.  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.  If patients do not experience improvement in pain and function at ≥90 MME/day, or if there are escalating dosage requirements, clinicians should discuss other approaches to pain management with the patient, consider working with patients to taper opioids to a lower dosage or to taper and discontinue opioids, and consider consulting a pain specialist. 

 

Established patients already taking high dosages of opioids, as well as patients transferring from other clinicians, might consider the possibility of opioid dosage reduction to be anxiety-provoking, and tapering opioids can be especially challenging after years on high dosages because of physical and psychological dependence.  However, these patients should be offered the opportunity to re-evaluate their continued use of opioids at high dosages in light of recent evidence regarding the association of opioid dosage and overdose risk.  Clinicians should explain in a nonjudgmental manner to patients already taking high opioid dosages (≥90 MME/day) that there is now an established body of scientific evidence showing that overdose risk is increased at higher opioid dosages.  Clinicians should empathically review benefits and risks of continued high-dosage opioid therapy and should offer to work with the patient to taper opioids to safer dosages.

 

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

 

Opioid use for acute pain (i.e., pain with abrupt onset and caused by an injury or other process that is not ongoing) is associated with long-term opioid use, and a greater amount of early opioid exposure is associated with greater risk for long-term use.  More than a few days of exposure to opioids significantly increases hazards, each day of unnecessary opioid use increases likelihood of physical dependence without adding benefit, and prescriptions with fewer days’ supply will minimize the number of pills available for unintentional or intentional diversion.

 

Acute pain can often be managed without opioids.  It is important to evaluate the patient for reversible causes of pain, for underlying etiologies with potentially serious sequelae, and to determine appropriate treatment.  When the diagnosis and severity of nontraumatic, nonsurgical acute pain are reasonably assumed to warrant the use of opioids, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids, often 3 days or less, unless circumstances clearly warrant additional opioid therapy.  More than 7 days will rarely be needed.  Clinicians should not prescribe additional opioids to patients “just in case” pain continues longer than expected.  Clinicians should re-evaluate the subset of patients who experience severe acute pain that continues longer than the expected duration to confirm or revise the initial diagnosis and to adjust management accordingly.  Given longer half-lives and longer duration of effects (e.g., respiratory depression) with ER/LA opioids such as methadone, fentanyl patches, or extended release versions of opioids such as oxycodone, oxymorphone, or morphine, clinicians should not prescribe ER/LA opioids for the treatment of acute pain.


 

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

 

Continuing opioid therapy for 3 months substantially increases risk for opioid use disorder ; therefore, follow-up earlier than 3 months might be necessary to provide the greatest opportunity to prevent the development of opioid use disorder.  In addition, risk for overdose associated with ER/LA opioids might be particularly high during the first 2 weeks of treatment .  Patients who do not have pain relief with opioids at 1 month are unlikely to experience pain relief with opioids at 6 months.  Reassessment of pain and function within 1 month of initiating opioids provides an opportunity to minimize risks of long-term opioid use by discontinuing opioids among patients not receiving a clear benefit from these medications.  Risks for opioid overdose are greatest during the first 3–7 days after opioid initiation or increase in dosage, particularly when methadone or transdermal fentanyl are prescribed.  Follow-up within 3 days is appropriate when initiating or increasing the dosage of methadone; and follow-up within 1 week might be appropriate when initiating or increasing the dosage of other ER/LA opioids.

 

Clinicians should evaluate patients to assess benefits and harms of opioids within 1 to 4 weeks of starting long-term opioid therapy or of dose escalation.  Clinicians should consider follow-up intervals within the lower end of this range when ER/LA opioids are started or increased or when total daily opioid dosage is ≥50 MME/day.  Shorter follow-up intervals (within 3 days) should be strongly considered when starting or increasing the dosage of methadone.  At follow up, clinicians should assess benefits in function, pain control, and quality of life using tools such as the three-item “Pain average, interference with Enjoyment of life, and interference with General activity” (PEG) Assessment Scale and/or asking patients about progress toward functional goals that have meaning for them.  Clinicians should also ask patients about common adverse effects such as constipation and drowsiness, as well as asking about and assessing for effects that might be early warning signs for more serious problems such as overdose (e.g., sedation or slurred speech) or opioid use disorder (e.g., craving, wanting to take opioids in greater quantities or more frequently than prescribed, or difficulty controlling use).  Clinicians should ask patients about their preferences for continuing opioids, given their effects on pain and function relative to any adverse effects experienced.

 

Clinicians should re-evaluate patients who are exposed to greater risk of opioid use disorder or overdose (e.g., patients with depression or other mental health conditions, a history of substance use disorder, a history of overdose, taking ≥50 MME/day, or taking other central nervous system depressants with opioids) more frequently than every 3 months.

Assessing Risk and Addressing Harms of Opioid Use

 

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

 

Certain risk factors are likely to increase susceptibility to opioid-associated harms and warrant incorporation of additional strategies into the management plan to mitigate risk.

 

9.  Clinicians should review the patient’s history of controlled substance prescriptions using the Prescription Monitoring Program (PMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose.  Clinicians should review PMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

 

Most fatal overdoses were associated with patients receiving opioids from multiple prescribers and/or with patients receiving high total daily opioid dosages.  Ideally, PMP data should be reviewed before every opioid prescription. 

 

If patients are found to have high opioid dosages, dangerous combinations of medications, or multiple controlled substance prescriptions written by different clinicians, several actions can be taken to augment clinicians’ abilities to improve patient safety: 

 

Clinicians should not dismiss patients from their practice solely on the basis of PMP information. 

 

10.  When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.

 

Concurrent use of opioid pain medications with other opioid pain medications, benzodiazepines, or heroin can increase patients’ risk for overdose.  Urine drug tests can provide information about drug use that is not reported by the patient.  In addition, urine drug tests can assist clinicians in identifying when patients are not taking opioids prescribed for them, which might in some cases indicate diversion or other clinically important issues such as difficulties with adverse effects.  However, routine toxicology screening will not provide definitive evidence of diversion.  To confirm such specific testing must be requested.

 

11.  Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.

 

Benzodiazepines and opioids both cause central nervous system depression and can decrease respiratory drive.  Concurrent use is likely to put patients at greater risk by quadrupling the risk for overdose death compared with opioid prescription alone.  Although there are circumstances when it might be appropriate to prescribe opioids to a patient receiving benzodiazepines (e.g., severe acute pain in a patient taking long-term, stable low-dose benzodiazepine therapy), clinicians should avoid prescribing opioids and benzodiazepines concurrently whenever possible.   Because of greater risks of benzodiazepine withdrawal relative to opioid withdrawal, and because tapering opioids can be associated with anxiety, when patients receiving both benzodiazepines and opioids require tapering to reduce risk for fatal respiratory depression, it might be safer and more practical to taper opioids first.  A commonly used tapering schedule that has been used safely and with moderate success is a reduction of the benzodiazepine dose by 25% every 1–2 weeks.

 

12.  Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

 

Opioid use disorder is defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) as a problematic pattern of opioid use leading to clinically significant impairment or distress. 

 

The prevalence of opioid dependence in primary care settings among patients with chronic pain on opioid therapy can be 3%–26% .  Opioid agonist or partial agonist treatment with methadone maintenance therapy or buprenorphine has been shown to be more effective in preventing relapse among patients with opioid use disorder. 

 

For patients meeting criteria for opioid use disorder, clinicians should offer or arrange for patients to receive evidence-based treatment, usually medication-assisted treatment with buprenorphine or methadone maintenance therapy in combination with behavioral therapies.

Abridged and modified from CDC Guideline for prescribing Opioids for Chronic Pain—United States 2016.