The use of opioid therapy for chronic non-cancer pain has increased substantially. Chronic opioid therapy is controversial, however, because of the potential for adverse effects and abuse. The American Pain Society and American Academy of Pain Medicine recently released a guideline for the use of opioids in patients with chronic noncancer pain. The multidisciplinary panel of experts graded the recommendations as strong or weak. A strong recommendation indicates that the benefits clearly outweigh the risks, whereas a weak recommendation indicates a closer balance of benefits to risks or weaker evidence. Decisions to follow weak recommendations should consider individual clinical circumstance, as well as patient preferences and values. The quality of evidence for each recommendation is graded as high, moderate, or low, depending on type, size, and number of studies; strength of associations or effects; and consistency of results among studies.

Recommendations

PATIENT SELECTION AND RISK STRATIFICATION

A history, physical examination, and appropriate testing should be performed before the initiation of therapy; benefits versus risks should be assessed before and during therapy. A trial of opioid therapy may be considered if pain is moderate or severe and affects the patient's quality of life, and if potential therapeutic benefits are likely to outweigh potential harms (Grade: strong recommendation, low-quality evidence).

Proper patient selection using benefit-to-risk assessment is crucial. Risk stratification should evaluate the potential for opioid abuse and risk of adverse effects. Reliable evidence supporting methods of predicting the benefits of chronic opioid therapy is limited. However, randomized trials show that opioid therapy is most beneficial in patients with moderate to severe pain who have not benefited from nonopioid therapy. Useful risk stratification tools are listed in Table 1. Patients with poorly defined pain conditions, a likely somatoform disorder, or unresolved compensation or legal issues may be less likely to benefit from therapy.

INFORMED CONSENT AND OPIOID MANAGEMENT PLANS

Informed consent should be obtained from patients before the initiation of therapy, and an ongoing discussion should include goals, expectations, potential risks, and alternative therapies (Grade: strong recommendation, low-quality evidence). Physicians may consider creating a written plan (Grade: weak recommendation, low-quality evidence).

Physicians and patients should discuss the risks and benefits of chronic opioid therapy before treatment and periodically during treatment. An informed consent process assists patients in making appropriate decisions that are consistent with their preferences and values. It is important for physicians to discuss the management plan with patients on an ongoing basis so that patients clearly understand the goals of treatment and have realistic expectations of treatment outcomes. A written plan can be helpful, especially in patients with a higher risk of abuse.

INITIATION AND TITRATION OF THERAPY

Initial treatment should be regarded as a therapeutic trial to determine whether chronic opioid therapy is appropriate. Opioid selection, initial dosing, and titration should be individualized based on the patient's health status, previous opioid use, therapeutic goals, and risk of adverse effects (Grade: strong recommendation, low-quality evidence).

An initial therapeutic trial should be administered for several weeks to months, guiding the decision to proceed with chronic therapy. Dosing is individualized and usually determined by incremental dosage escalation, as long as no serious adverse effects occur. Evidence is insufficient to recommend one opioid over another; however, short-acting opioids are probably safer for initial therapy because there is less risk of inadvertent overdose. Transitioning to around-the-clock dosing of long-acting opioids may lead to more consistent pain control, improved adherence, and lower risk of abuse.

METHADONE

If methadone is used, it should be initiated and titrated cautiously by a physician familiar with its use and risks (Grade: strong recommendation, moderate-quality evidence).

The use of methadone for chronic noncancer pain has increased; however, few trials have evaluated its risks and benefits. In addition, several epidemiologic studies suggest an increase in methadone-related deaths in the United States. Prescribing physicians should be familiar with its complicated and variable pharmacodynamics, and potential risks. Methadone dosing relative to other opioids is variable, and conversion to methadone should be performed cautiously.

MONITORING

Patients should be reassessed periodically and when warranted by changing circumstances (Grade: strong recommendation, low-quality evidence). Urine drug testing or other methods to determine adherence should be performed in patients at high risk of aberrant drug-related behaviors (Grade: strong recommendation, low-quality evidence), and considered in patients at low risk (Grade: weak recommendation, low-quality evidence).

Regular monitoring of all patients undergoing chronic opioid therapy is important in determining whether the treatment is benefiting the patient, assessing whether restructuring the treatment plan or adding additional services would be helpful, and reevaluating the benefits versus risks. Risk stratification is useful in guiding the intensity and frequency of monitoring. Regular, repeated assessments that address a variety of factors are likely to be most effective. Because self-report may be unreliable for determining adherence, other methods (e.g., urine drug screening, pill counts, caregiver interviews) may be considered.

HIGH-RISK PATIENTS

Chronic opioid therapy may be used in patients with a history of drug abuse, psychiatric issues, or serious aberrant drug-related behaviors only if more stringent monitoring is implemented. However, consultation with a mental health or addiction subspecialist should be strongly considered. If a patient undergoing chronic opioid therapy engages in aberrant drug-related behavior, use of the therapy should be reevaluated (Grade: strong recommendation, low-quality evidence).

Chronic noncancer pain is common in patients with a history of drug abuse, psychiatric issues, or serious aberrant drug-related behaviors. Although the use of chronic opioid therapy is challenging in these patients, it may be beneficial to some. Potential risks may be minimized with more frequent and intense monitoring, limited prescription quantities, prescription monitoring programs, and physician consultation with a mental health or addiction subspecialist. If aberrant behavior occurs, reevaluation of the use of chronic opioid therapy is required. However, the physician's response should consider the seriousness of the behavior, the cause of the behavior, the likelihood that the behavior will recur, and the clinical context.

HIGHER DOSAGES AND DISCONTINUATION OF THERAPY

When repeated dosage escalations occur, physicians should evaluate potential causes and reassess benefits versus harms (Grade: strong recommendation, low-quality evidence). In patients who require relatively high dosages of therapy, physicians should regularly evaluate for unique opioid-related adverse effects, changes in health status, and adherence; more frequent follow-up should be considered (Grade: strong recommendation, low-quality evidence.) Opioid rotation should be considered if intolerable adverse effects occur or if treatment benefit is inadequate (Grade: weak recommendation, low-quality evidence). Chronic opioid therapy should be tapered or weaned in patients who engage in aberrant drug-related behavior, have no progress toward therapeutic goals, or experience intolerable adverse effects (Grade: strong recommendation, low-quality evidence).

Progressively higher opioid dosages may improve pain control in some patients, but repeated escalations may have limited usefulness and may be a marker for substance use disorder or diversion. There is little evidence to guide opioid prescribing at higher dosages. However, when dosages reach 200 mg of morphine daily, or the equivalent, increased monitoring may be appropriate. Rotating different opioids is an option for some patients who have intolerable adverse effects or inadequate benefit of treatment despite dosage increases. Tapering or weaning of therapy often can be achieved in an outpatient setting. A slower dosage reduction may reduce withdrawal effects, and referral to a detoxification program may be beneficial.

ADVERSE EFFECTS

Physicians should anticipate, identify, and treat common opioid-related adverse effects (Grade: strong recommendation, moderate-quality evidence).

Anticipation and treatment of adverse effects help maintain a favorable balance of benefits to harms, decrease the risk of discontinuation, and may allow for the use of higher opioid dosages if needed. Constipation and nausea/vomiting are common adverse effects associated with opioid use. Sedation, pruritus, and myoclonus are also possible.

PSYCHOTHERAPEUTIC COINTERVENTIONS

Adjunctive nonopioid therapy, such as psychotherapeutic interventions, functional restoration, and interdisciplinary therapy, should be routinely added to chronic opioid therapy in patients with chronic noncancer pain (Grade: strong recommendation, moderate-quality evidence).

When chronic noncancer pain is accompanied by comorbidities, impaired function, or psychological disturbances, chronic opioid therapy is most effective when part of a multimodality treatment strategy. Cognitive behavior therapy has consistently been shown to be effective in patients with chronic noncancer pain. Other adjunctive treatment strategies include progressive relaxation, biofeedback, functional restoration, and inter- or multidisciplinary pain management approaches.

OPIOID-RELATED COGNITIVE IMPAIRMENT

Physicians should counsel patients about transient or lasting cognitive impairment from chronic opioid therapy that may affect driving and work safety (Grade: strong recommendation, low-quality evidence).

Opioid use may cause somnolence, clouded mentation, decreased concentration, and slower reflexes. Patients should be counseled not to drive or engage in potentially dangerous activities when impaired, and that the risk of impairment is higher with treatment initiation, with dosage increases, and when combining opioids with other drugs or substances that effect the central nervous system (e.g., alcohol).

MEDICAL HOME AND CONSULTATION

Patients should identify a physician to coordinate consultation and communication among all health care professionals involved in the patient's care (Grade: strong recommendation, low-quality evidence). Consultation, including interdisciplinary pain management, should be pursued if the patient may benefit from additional skills or resources (Grade: strong recommendation, moderate-quality evidence).

Studies have shown that patients have better outcomes when they have a physician who accepts primary responsibility for most of their care and coordinates the care from other physicians when needed. This medical home model does not require the primary physician to prescribe and monitor the patient's chronic opioid therapy, although the physician's coordination of other resources (e.g., pain centers) is crucial.

BREAKTHROUGH PAIN

If patients undergoing around-the-clock chronic opioid therapy have breakthrough pain, physicians may consider as-needed administration based on the initial and ongoing assessment of benefits versus risks (Grade: weak recommendation, low-quality evidence).

Breakthrough pain may not be related to the underlying condition; therefore, its assessment, including diagnostic testing, follow-up, and possible referral, should be separate from that of baseline pain. Additional as-needed opioid therapy is an option for breakthrough pain; however, the therapeutic benefits should be weighed carefully against the potential harms, and nonpharmacologic and nonopioid therapies should be considered.