Pain Management and Opioids

TOPIC 3 SUMMARY

Basics of Opioid
Prescribing — Part I

INTRODUCTION AND GENERAL PRINCIPLES

Prescription opioids are medications that work as agonists at the opioid receptors, which
are distributed throughout the brain, spinal cord, peripheral nerves, and digestive track.
These medications can be classified as follows:

DESCRIPTION EXAMPLES
Natural opiates Derived from the opium Codeine, morphine
poppy
Semisynthetic opioids Directly derived from natural Hydrocodone, hydromorphone,
opiates oxycodone, oxymorphone, and
buprenorphine
Synthetic opioids Created in the laboratory Methadone, meperidine, and fentanyl

Opioids are powerful analgesic medications that can be effective in treating chronic
pain. They work by directly affecting ascending and descending pain signals in the cen-
tral nervous system and preventing activation of peripheral nociceptors. All opioids also
activate the reward system in the brain and, with chronic exposure, cause physiologic
adaptations, namely tolerance and physical dependence.

Opioids also have the potential to cause severe adverse effects, and opioid misuse can
be fatal. The challenge for the clinician then is to reduce opioid prescriptions where
possible while ensuring safer prescribing when indicated.

WHEN TO CONSIDER OPIOID THERAPY FOR CHRONIC PAIN

Nonpharmacologic therapies and nonopioid therapies are preferred for management
of chronic non–cancer-related pain and can also be effective in patients with cancer-

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related pain. These therapies include acetaminophen, nonsteroidal antiinflammatory
drugs (NSAIDs), medications with proven benefit for neuropathic pain (serotonin–
norepinephrine reuptake inhibitors, tricyclic antidepressants, gabapentinoids), and top-
ical agents such as lidocaine or capsaicin. Engagement in self-management is important
in chronic pain as in all chronic illnesses.

Opioids are not first-line therapy for chronic non–cancer-related pain because of their
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 pain has not responded favorably 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.

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

STEPS FOR INITIATING OPIOID THERAPY

Opioid therapy should only be initiated after careful considerations of the risks and
benefits of treatment, and every effort should be made to reduce the risks. The steps are
as follows:

1. Determine whether there is an indication for opioid therapy.

2. 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 very specific time frame

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

as helpful.

4. Assess the potential risks of opioid therapy, including:

• Risk of misuse (discussed below)
• Medical risks, such as sleep apnea, renal or hepatic dysfunction, or use of other
central nervous system (CNS) depressants

5. Consider referral to an appropriate specialist if you identify a high risk of misuse or

a need for interventional pain management.
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6. 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)

7. Ensure that the patient has naloxone at home.

8. For opioid-naive patients, start with a short-acting agent.

• In general, these agents should be initiated at a low dose and kept at the lowest
dose possible.
• Exercise caution with dosing in patients with risks such as 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, they may
transition to an extended-release/long-acting (ER/LA) opioid. The main reason to do
this is the longer duration of analgesia; studies have not demonstrated any substantial
benefit otherwise. Of note, there is a higher risk of harm with misuse of ER/LA opioids
because of the concentrated doses. Patients must be instructed to never disrupt (e.g.,
break or crush) the ER/LA opioid formulation.
Risk of Opioid Misuse and Opioid Use Disorder
One of the major risks of opioid therapy is the potential for misuse. Medication misuse
is defined as use contrary to the prescribed use, regardless of the presence or absence of
harm or adverse effects. Opioid use disorder (OUD) is defined as a pattern of continued
opioid use with experience of, or potential for, harm. All patients should be evaluated for
risk of opioid misuse before being prescribed opioids; this includes patients receiving
opioid analgesics for cancer-related pain.

A multifaceted approach is needed to help identify patients at risk. The first step is a
patient interview and medical record review to identify risk factors for the development
of OUD. These include:

• Longer duration of opioid use

• Higher-dose opioid use
• Personal history of OUD
• Personal or family history of any substance use disorder (tobacco, alcohol,
cannabis, or other substances)
• Personal history of major depressive disorder
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 • Use of psychotropic medications
• Age <40 years
• History of sexual trauma
• Lack of employment

Other important steps in this approach include:

• Communication with past prescribers

• Review of old medical records
• Focused physical examination for signs of opioid use (e.g., injection sites, signs
of intoxication or withdrawal)
• Review of the state’s PDMP
• Urine drug testing

Formal screening tools can be used to help identify patients at risk for misuse (see Tools
for Clinical Practice below), but they do not reliably predict misuse and should therefore
be used only with other clinical information, including longitudinal monitoring.

Importantly, even individuals who are initially deemed to be at low risk for misuse are
still at some risk. Furthermore, the risk of misuse can change over time. All patients
should therefore be monitored for misuse or risk of misuse with:

• Face-to-face evaluations (interview and examination)

• Intermittent urine drug testing
• Intermittent pill counts
• PDMP checks
• Communication with co–care providers and significant others as indicated

Moderate- and higher-risk patients may be candidates for opioid therapy but should be
monitored with greater frequency and provided more support; in these cases, comanage-
ment with an addiction medicine, psychiatric, or pain specialist should be considered as
appropriate.
If misuse of a medication is identified, the patient should be assessed for a substance
use disorder, and there should be either tightening of prescribing to assure safety or
tapering and cessation of opioids.

ASSESSING RESPONSE TO OPIOID THERAPY

The general goals of opioid therapy are to reduce pain, improve quality or enjoyment of
life, and enhance function or activity level.

Response to treatment should be assessed at each visit; therapy can be continued if there
is good analgesia, improved function and quality of life, no or manageable adverse
effects, and no misuse or risk behaviors.

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Several scales are available to assess response to treatment. Unidimensional pain scales
(numerical rating scales) assess only the intensity of pain, whereas multidimensional
pain scales assess the intensity of pain as well as its effect on function and quality of
life. An example is PEG, a short, validated assessment scale with a 0-to-10 rating for
each of three dimensions: Pain intensity, Enjoyment of life, and General activity level. A
30% improvement is considered clinically meaningful. Achieving complete relief of pain
may not be possible in some cases.
Worsening Pain
If a patient reports worsening pain after previous control on a stable opioid regimen, a
variety of causes and corresponding interventions should be considered:

CAUSE INTERVENTION
Disease progression • Rule out disease progression as appropriate.
Co-occurring distress, such as increased • Advise lifestyle changes, medical interventions,
stress, depression, anxiety, poor sleep, or counseling, or referrals as indicated.
changes in physical activity
Opioid tolerance • If doses are low and tolerance is suspected: Consider
increasing the dose. Of note, it can take 5 half-lives
(2–3 days for most opioids) before the full effect of
the increased dose is apparent.

• If doses are higher and tolerance is suspected:

Consider rotating to an alternative opioid.
Withdrawal-mediated pain (due to • If frequent doses of a short-acting opioid are being
fluctuating blood opioid levels) used, consider a change to long-acting.
Opioid-induced hyperalgesia (increasing • Consider tapering (as the pain may improve off
diffuse pain worsened with increased opioids or with lower doses) or rotating to an
opioids and lessened with reduced alternative opioid.
opioids)
Opioid misuse or OUD (signaled by loss • Evaluate for OUD or refer for assessment.
of control, compulsive use, continued use
• Control opioids for safety, or transition to opioid
despite adverse consequences, craving)
agonist therapy for OUD (buprenorphine by qualified
prescribers or methadone treatment in a licensed
opioid treatment program).
Diversion • Discontinue opioids if there is evidence or strong
suspicion of diversion.

Breakthrough Pain
In patients taking ER/LA opioids, breakthrough pain can occur. This happens most
commonly with physical activity, stressors, or other triggers but can also occur sponta-
neously in some conditions (e.g., cancer, certain neuropathies).

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Management options for breakthrough pain include:

• Lifestyle adjustments to limit triggers as reasonable

• Self-management interventions when effective, including cold, heat, stretching,
transcutaneous electrical nerve stimulation (TENS), meditation, breathing, mild
exercise, and change of focus
• Use of nonopioids, including NSAIDs or acetaminophen, as helpful

Judicious, occasional use of short-acting opioids may be appropriate in some patients.

Common Adverse Effects
Opioids have a range of adverse effects, and patients should be assessed for these at each
visit. Many adverse effects are transient, except for constipation, which is the most com-
mon adverse effect from chronic opioid use and often persists. The table on page 7 lists
some of the most common adverse effects of opioids, along with specific management
strategies.

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 needed

OPIOID ROTATION
Opioid rotation may be beneficial not only in the setting of persistent adverse effects but
also in other situations, such as:

• Poor analgesic response

• Progressive tolerance to initial analgesia
• Opioid-induced hyperalgesia
• Risks associated with high-dose opioids

When patients rotate opioids, they generally end up taking a lower dose (as measured in
morphine milligram equivalents [MMEs]), so there are often fewer adverse effects but at
least an equivalent analgesic response. However, there are limited data on the effective-
ness of opioid rotation.

In addition, because of unpredictable cross-tolerance, patients may develop sedation and

overdose (or pain and withdrawal) on the new opioid, so caution and careful monitoring
are advised.

(continued on page 17)

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 ADVERSE EFFECTS OF OPIOIDS MANAGEMENT STRATEGIES
Constipation (due to opioid • Advise preventive measures, including using the lowest effective
receptor binding in the gut) doses of opioids, increasing fluid and fiber intake, and increasing
physical activity.

• Recommend a bowel stimulant (e.g., senna) in combination with

either a stool softener (e.g., docusate) or bulking agent (e.g.,
psyllium) for prevention and/or treatment.

• If the constipation is persistent, consider a peripherally acting

mu opioid antagonist (PAMORA), such as methylnaltrexone or
naloxegol.
Sedation/psychomotor and • Advise patient not to drive, operate heavy machinery, or engage in
cognitive impairment (most work requiring close attention until they are without sedation or
common with initial use, cognitive blurring, which often requires at least one week on the new
intermittent use, an increased dose, opioid regimen.
or rotation to a new opioid; usually
• Consider discontinuing other sedative medications if possible.
resolves as tolerance develops)
• If sedation persists, consider reducing the opioid dose or rotation to
a different opioid.
Urinary retention (usually mild) • If persistent, reduce the opioid dose, rotate to an alternative opioid,
or both.
Pruritus (usually mild) • If persistent, reduce the opioid dose, rotate to an alternative opioid,
or both.

• Consider short-term antihistamine therapy.

Nausea and vomiting (usually • Consider short-term antiemetic therapy.
resolve quickly)
Male hypogonadism or abnormal • Measure appropriate hormone levels if indicated based on
menstrual cycles, with reduced symptoms, and consider sex hormone replacement.
bone density (due to suppression
• Consider obtaining dual-energy x-ray absorptiometry in patients with
of hypothalamic–pituitary–gonadal
confirmed hypogonadism.
function)
Low cortisol or adrenocorticotropic • Consider evaluation for adrenal insufficiency and glucocorticoid
hormone (ACTH) levels/adrenal replacement therapy in select patients.
insufficiency (due to suppression
of hypothalamic–pituitary–adrenal
function)

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Steps to Rotating Opioids
A complete opioid rotation involves the following steps:

1. Determine the total usual dose of each opioid per 24 hours.

2. C
 onvert the 24-hour intake of each opioid to MMEs using equivalency charts or
conversion factors, and determine the current total daily MME.
• Although opioid equivalency charts are useful, they are based on single studies in
non–opioid-tolerant, healthy volunteers and do not reflect individual differences
in genetics, comorbidities, or polypharmacy.

3. Calculate the equivalent 24-hour MME dose of the new opioid.

4. R
 educe the calculated daily dose by 25% to 75% to account for incomplete
cross-tolerance. (Greater reductions may be required for methadone.)
5. P
 rescribe the new opioid at the reduced calculated dose in appropriately divided
doses (once or twice daily for most ER/LA opioids). Consider making immediate-
release opioids available to the patient in case of increased pain.

6. Monitor carefully and adjust for sedation, adverse effects, or unrelieved pain.

TOOLS FOR CLINICAL PRACTICE

Screening for Risk of Opioid Misuse
• Opioid Risk Tool (ORT) (9-item scale)
• Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R)
(24-item scale)
• Diagnosis, Intractability, Risk, and Efficacy Inventory (DIRE) (8-item scale)
Counseling Patients About Opioid Therapy
• Prescription Opioids: What You Need to Know: A 2-page document for patients
(from the U.S. Centers for Disease Control and Prevention) that lists the risks
and adverse effects of opioids as well as safety-related steps that patients can
take
Sample Patient–Provider Agreements from:
• Boston Medical Center
• U.S. Food and Drug Administration
Assessing Pain Intensity and Interference
• Brief Pain Inventory (15-item scale)
• PEG assessment tool (3-item scale derived from the Brief Pain Inventory)
• Roland Morris Disability Questionnaire (24-item scale to assess low back pain
specifically)

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MME Charts and Calculators
• Calculating Total Daily Dose of Opioids for Safer Dosage (from the U.S. Centers
for Disease Control and Prevention)
• Opioid Conversion Calculator (from Oregon Pain Guidance)
• Opioid Conversion Calculator Morphine Equivalents — Advanced (from Global RPh)

LEARNING RESOURCES
• Opioid Efficacy for Chronic Pain: A slide (from Boston University School of
Medicine) summarizing the available evidence on the use of opioids for chronic
pain
• Minimum Level of Monitoring Based on Risk: A chart (from Boston University
School of Medicine) showing how frequently various tools should be used to
monitor opioid safety depending on the patient’s risk for opioid misuse
• Rotating Opioids to Manage Chronic Pain: An infographic from NEJM
Knowledge+ that describes why opioid rotations work, when to consider opioid
rotation, what to consider when selecting a new drug and the dose of the new
drug, how to counsel patients during a rotation, and the steps involved in one
rotation method.
• The Role of the Pain Psychologist in Managing Chronic Pain: An infographic
from NEJM Knowledge+ on the biopsychosocial model of pain, referring a
patient to a pain psychologist, the pain psychology assessment, and common
pain psychology interventions

Last reviewed Oct 2023. Last modified Oct 2023. The information included here is provided
for educational purposes only. It is not intended as a sole source on the subject matter or as
a substitute for the professional judgment of qualified health care professionals. Users are
advised, whenever possible, to confirm the information through additional sources.

© 2023 Massachusetts Medical Society. All rights reserved.

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