Chronic Pain and Opioids

Caring for patients with chronic non-cancer-related pain is a clinical challenge. In many regions of the United States, increased rates of opioid misuse and overdose have led to opioid-prescribing restrictions. Health care providers (including resident physicians) should understand and utilize evidence-based treatments when caring for patients with chronic pain, reducing opioid prescriptions whenever possible and ensuring safer prescribing, when indicated.

• Key Principles for Assessing Chronic Pain

• Key Principles for Managing Chronic Pain

• Opioid Therapy

• Fibromyalgia

In 2016, the Centers for Disease Control and Prevention (CDC) released an important guideline for prescribing opioids for chronic noncancer and nonpalliative pain.

Key Principles for Assessing Chronic Pain

• Begin with a thorough physical examination and history. Key portions of the history include previous therapies; exacerbating and alleviating features; duration and severity; location; mechanism of any previous injuries; and presence of alarm features, including but not limited to neurologic deficits, fevers, and weight loss.

• Review the patient’s functional status, including activities of daily living and instrumental activities of daily living.

• Screen for comorbid mood disorders and substance use disorders in all patients.

Key Principles for Managing Chronic Pain

• A multimodal treatment strategy is the foundation of chronic pain management. Nonpharmacologic therapy (physical therapy, exercise therapy, weight loss, and cognitive behavioral techniques), nonopioid pharmacologic therapy (acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], certain antidepressants, and anticonvulsants), and interventional approaches (injections) are preferred first-line options for chronic pain.

• Treatment goals and expectations should be discussed and agreed upon between the physician and the patient.

• Consider a trial of opioids if the benefits of treating a patient’s pain and function are anticipated to outweigh the risks.

• When prescribing opioids:

  • Where appropriate, combine nonpharmacologic therapy and nonopioid pharmacologic therapy.

  • Start with immediate-release opioids at the lowest effective dosage (“start low, go slow”).

  • Avoid prescribing opioids with concomitant benzodiazepines, which increases risk for respiratory depression.

  • Establish treatment goals, including realistic goals for what pain control can be achieved and an anticipated timeline for weaning opioids, in a structured patient-provider agreement.

  • Schedule frequent face-to-face visits to assess the risks and benefits of therapy, do random urine drug testing and pill counts to evaluate for misuse or diversion, and use a structured assessment of adverse effects and functional improvements at each visit.

  • Review state prescription-drug-monitoring programs.

  • Offer naloxone to individuals at increased risk for overdose, especially those taking higher daily doses of opioid medications.

  • Ensure the patient is placed on a daily bowel regimen and monitored for opioid-induced constipation.

Opioid Therapy

Opioids are a mainstay of treatment for severe cancer pain and can help achieve pain control in 70% to 90% of patients. Opioids are also beneficial for symptom control in palliative and end-of-life care.

Opioids are not first-line therapy for chronic non-cancer-related pain because of potential risks, lack of evidence of long-term efficacy, and the possibility of tolerance or hyperalgesia. However, opioids may be appropriate on a trial basis for patients with chronic pain if the following conditions are met:

• The pain is severe and has a significant effect on function and quality of life.

• The patient has not had a favorable response to other appropriate interventions, or the other available interventions represent higher risk (e.g., NSAIDs in a patient with chronic kidney disease).

• The benefits of opioid therapy are expected to outweigh the risks.

When initiating opioid therapy, consider the following steps:

• Determine whether there is an indication for opioid therapy.

• Establish clear functional goals with the patient. Goals should be SMART:

  • Specific about what the patient will set out to do

  • Measurable, so that you and the patient can determine whether the goal has been met

  • Action-oriented (rather than passive)

  • Realistic with respect to the patient’s current condition

  • Time-bound, so that the goal is being measured within a specific time frame

• Plan to continue nonopioid medications for complementary and synergistic effects.

• Assess the potential risks of opioid therapy, including:

  • risk of misuse

  • medical risks, such as sleep apnea, obesity hypoventilation syndrome, renal or hepatic dysfunction, or use of other central nervous system (CNS) depressants

• Consider referral to an appropriate specialist, if you identify a high risk of misuse or a need for interventional pain management

• Institute a patient-provider agreement. Such agreements typically outline the following:

  • the planned frequency of follow-up visits to assess pain, function, adverse effects, and progress toward established goals; follow-up is typically at least every 4 weeks initially, progressing to at least every 3 months

  • review of all medications in the planned regimen, including name, dose, frequency, and instructions for taking the medication

  • review of risky medication-associated behaviors, such as requesting early refills or obtaining refills for controlled substances from other providers

  • tools to be used for risk monitoring, such as urine drug testing, pill counts, and reports from the prescription drug monitoring program (PDMP)

• Provide an at-home naloxone rescue kit.

• For opioid-naive patients, start with a short-acting agent:

  • In general, initiate these agents at a low dose and keep at the lowest dose possible.

  • Exercise caution with dosing in patients with risks, including obstructive sleep apnea, hepatic or renal dysfunction, or concomitant use of other CNS depressants.

    • Once a patient has been taking a short-acting opioid for at least one week, he or she may transition to an extended-release/long-acting opioid, as indicated. Opioids should only be continued in patients who have documented benefit after a trial of these medications.

Drug-Drug Interactions

Clinicians should be aware of potential drug-drug interactions prior to initiating opioid therapy. Certain opioids, such as fentanyl, codeine, oxycodone, methadone, and tramadol, are metabolized by the liver’s cytochrome P-450 (CYP450) enzymes. Medications that inhibit the CYP450 pathway have the potential to reduce the clearance of these opioids and lead to dangerous dose accumulation, thus placing the patient at risk for unintentional opioid overdose.

Several types of medications, including those listed below, should be avoided in the setting of opioid therapy because of potentiating effects on sedation and respiratory depression:

• benzodiazepines

• sedative hypnotics

• tricyclic antidepressants

• monoamine oxidase inhibitors

Monitoring Response

The patient’s response to therapy should be assessed at each follow-up appointment. A validated pain-assessment scale should be used to assist in response to treatment assessment. One example is the PEG scale, which assesses pain across three dimensions:

• Pain intensity

• Enjoyment of life

• General activity level

Adverse effects:

Patients should be monitored for adverse effects of opioid therapy including:

• constipation

• urinary retention

• psychomotor impairment or falls

• cognitive impairment

• pruritus, nausea, and vomiting

If an adverse effect persists, general management approaches include:

• reducing the opioid dose

• switching to an alternative opioid (known as opioid rotation)

• treating the adverse effect with medication, if unable to tolerate adverse effects or unable to rotate opioids

Rotating Opioids

When patients rotate opioids, they generally take a lower dose and often experience fewer adverse effects with an equivalent analgesic response. In addition, because of unpredictable cross-tolerance, patients may develop sedation and overdose (or pain and withdrawal) on the new opioid. Therefore, caution and careful monitoring are advised when rotating opioid medications.

Fibromyalgia

Fibromyalgia is a well-defined chronic pain syndrome with a prevalence of 2% to 4%. It is characterized by widespread musculoskeletal pain for at least 3 months in the absence of any inflammatory or metabolic cause and remains a clinical diagnosis of exclusion. It also often involves a combination of chronic fatigue, sleep disturbances, cognitive difficulties, depressed mood, anxiety, headaches, and digestive problems, such as irritable bowel syndrome.

The American College of Rheumatology (ACR) established diagnostic criteria in 1990 and 2010, with a slight revision in 2016 to include a generalized pain criterion.

• 1990 ACR diagnostic criteria: at least 11 out of 18 positive tender points

• 2016 ACR diagnostic criteria: a widespread pain index ≥7 and a symptom severity scale score ≥5 or a widespread pain index 4-6 and a symptom severity scale score ≥9; patients must have pain symptoms in ≥4 of 5 regions

Treatment of fibromyalgia involves both pharmacologic and nonpharmacologic therapy (e.g., graded activity, meditation, and cognitive behavioral techniques). The three FDA-approved medications for fibromyalgia are duloxetine, milnacipran, and pregabalin. Gabapentin and tricyclic antidepressants are also frequently used but may carry a higher risk of adverse effects. Opioids are not recommended.

See an NEJM Knowledge+ infographic on diagnosis and treatment of fibromyalgia.