Pain Management and Opioids

TOPIC 4 SUMMARY

Basics of Opioid
Prescribing — Part II

INTRODUCTION AND GENERAL PRINCIPLES

Managing opioid therapy in a patient with chronic pain comes with a host of clinical
considerations, including making decisions about short-acting versus long-acting opi-
oids; mitigating and managing the risk for misuse, including addiction and overdose;
and deciding when and how to taper the opioid, if necessary.

SHORT-ACTING VS. EXTENDED-RELEASE/LONG-ACTING OPIOIDS

Opioid analgesics can be divided into two groups: short-acting opioids and extended-
release/long-acting (ER/LA) opioids. Overall, the two types of medications have similar
efficacy and are associated with a similar risk for developing misuse. Thus, the decision
of which type to use depends on the individual clinical scenario, with a goal of meeting
the patient’s specific needs and preferences. Indications for these medications as well as
their features and risks are shown in the table on page 2.
Switching from a Short-Acting Opioid to an ER/LA Opioid
Switching from short-acting to ER/LA opioids is simplest if the same opioid molecule
is used, because there is no concern about lack of cross-tolerance, and thus the patient
can transition to the same total daily dose. Often, patients are even able to transi-
tion to a somewhat lower total daily dose, because the extended-release opioid largely
avoids peaks and troughs in drug levels and, as a result, may provide more-stable and
improved analgesia.

If a patient is switched from a short-acting opioid to a different, ER/LA opioid molecule,

the process is the same as when a patient rotates from one ER/LA opioid to another,
given uncertainty about individual responses to the new opioid in terms of both anal-
gesia and adverse effects. For more details about opioid rotation, see Topic 3: Basics of
Opioid Prescribing — Part I.

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 SHORT-ACTING OPIOIDS
Indications • Intermittent or occasional pain
• Severe pain in opioid-naive patients
Features • Analgesia typically lasts 3 to 6 hours
• Easier to safely titrate for symptom control
• Provide intermittent relief for (a) pain that
is intermittent and for (b) pain that is
persistent but from which a patient seeks
only intermittent relief
• Can provide around-the-clock pain relief
when dosed at appropriately spaced
intervals
Risks • May lead to end-of-dose lapses in pain
control, including waking during the night
with pain
• Frequent dosing for around-the-clock
analgesia may be disruptive
• Fluctuations in blood levels may result
in withdrawal-mediated symptoms in
physically dependent patients, including
increased pain, distress, irritability, or
other symptoms
Examples • Codeine
• Immediate-release formulations of
morphine, hydrocodone, hydromorphone,
oxycodone, oxymorphone, tramadol,
tapentadol, and fentanyl
Topic 4: Basics of Opioid Prescribing — Part II
ER/LA OPIOIDS
• Severe pain requiring around-the-clock,
long-term relief when other interventions
have not provided adequate symptom
control
• Should only be used in patients who have
developed opioid tolerance (defined as
taking at least 60 morphine milligram
equivalents [MMEs] daily of a short-acting
opioid for at least one week)
• More-stable blood levels, resulting in less
fluctuation in analgesia
• Reduce risk for opioid withdrawal–
mediated pain
• May have increased risk of overdose
compared with short-acting opioids,
especially when the dose is initiated or
increased. Should therefore be used with
particular caution in patients with hepatic
or renal dysfunction, sleep apnea, or
concomitant use of benzodiazepines or
other sedative hypnotics
• Higher risk of overdose if a patient
disrupts the extended-release mechanism,
leading to rapid absorption of a high dose
of opioid
• Fentanyl and buprenorphine patches
• Methadone
• Extended-release formulations of the
short-acting opioids listed to the left
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RISK OF RESPIRATORY DEPRESSION, SEDATION, AND OVERDOSE
One of the major risks associated with opioid use is opioid overdose, characterized
by sedation, respiratory depression, and potentially death. Opioids cause respiratory
depression by depressing the medullary respiratory center, resulting in reductions in
tidal volume, minute ventilation, and responsiveness to carbon dioxide. Therefore,
patients and family should be educated about manifestations of opioid overdose, ways
to prevent overdose, and use of naloxone if overdose is suspected.

Some of the major risk factors for opioid overdose are:

• Concurrent use of sedative medications, including benzodiazepines

• Coexisting mental health or substance use disorder
• Higher doses of opioids (especially >100 MMEs daily)
• Prior opioid overdose
• Use of ER/LA opioid formulations
• Older age (>65)
• Sleep-disordered breathing

In addition, patients are more likely to overdose during initiation of treatment (espe-
cially the first 2 weeks of treatment with ER/LA opioids), with dose increases, and after
incarceration or rehabilitation (because their opioid tolerance has diminished).
Calculating and Managing Risk
The revised Risk Index for Overdose or Severe Opioid-Induced Respiratory Depression
(RIOSORD) is a validated instrument that uses the risk factors above to estimate the risk
for overdose in opioid-treated patients. When an opioid prescription is necessary in a
patient at high calculated risk for respiratory depression, clinicians should:

• Put interventions in place to reduce risk factors

• Prescribe naloxone
• Consider buprenorphine (a partial opioid agonist) as the best opioid option,
given its ceiling effect and therefore lower risk of respiratory depression

Concurrent use of benzodiazepines is seen in 30% of opioid overdoses nationally.

Therefore, when managing anxiety and related disorders in patients taking opioids,
clinicians should consider approaches other than benzodiazepines, such as psycholog-
ical therapies (e.g., cognitive behavioral therapy, acceptance and commitment ther-
apy, mindfulness-based stress reduction) or a carefully dosed nonsedative medication,
such as a selective serotonin-reuptake inhibitor (SSRI) or a serotonin–norepinephrine
reuptake inhibitor (SNRI).

If a benzodiazepine must be added or continued when an opioid is part of a patient’s

therapy, the patient should be counseled on the added risk and instructed to hold medi-
cation doses if sedated and not increase the dose of either medication without consulting
the prescriber.

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Sleep-Disordered Breathing
Opioid-induced changes in respiratory function are also seen during sleep. Sleep-
disordered breathing affects up to 70% of patients on chronic opioid therapy and is
often unrecognized. The two types of sleep apnea, described below, may occur together
and compound patient risk.

• Central sleep apnea can occur because opioids reduce the ventilatory response to
carbon dioxide and hypoxemia, which leads to slowing of one’s breathing and
potential apnea. Risk increases with the opioid dose and with concurrent use of
benzodiazepines, alcohol, or other sedative hypnotics.
• Obstructive sleep apnea can occur because of soft-tissue obstruction in the airway
and is more common with but not limited to higher BMIs.

Common signs and symptoms of sleep apnea include poor concentration, daytime
sleepiness, morning headaches, insomnia, nightmares, snoring, depression, irritability,
mood swings, and difficult-to-control pain related to poor sleep quality.

When sleep apnea is suspected, a sleep study should be performed and medications
adjusted to improve safety.

MONITORING AND MANAGING PSYCHIATRIC COMORBIDITIES IN

CHRONIC PAIN
Chronic pain often leads to increased stress, depression, and anxiety, and preexisting
depression and anxiety are risk factors for the development of chronic pain. Thus, cli-
nicians should screen all patients with chronic pain for psychiatric comorbidities using
a brief, validated assessment tool (see Tools for Clinical Practice below). Effectively
addressing such comorbidities can often reduce the experience of pain.
If a mood disorder is present:

• Engage the patient in counseling aimed at both mood management and self-
management of pain.
• Consider antidepressant therapy, but be aware of drug–drug interactions.
– Serotonin syndrome may occur when opioids are combined with monoamine
oxidase inhibitors, tricyclic antidepressants, or SNRIs. The risk is greater
with opioids such as tramadol and tapentadol that have nonopioid analgesic
mechanisms involving serotonin or norepinephrine reuptake inhibition.
– Some antidepressants inhibit metabolism through certain cytochrome P-450
pathways, thus increasing blood levels of opioids that utilize these pathways
for elimination.

MONITORING FOR UNSAFE OPIOID USE

When opioid therapy is prescribed, a strict plan should be put into place to monitor for
unsafe opioid use, including misuse and diversion. Key monitoring tools include pill

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counts, urine drug testing, and reports from the state’s prescription drug monitoring
program (PDMP). Pill counts involve asking the patient to bring their opioid into the
office, and the number of pills is counted and compared with the expected number of
pills based on the prescribed amount. Urine drug testing is discussed in further detail
in Topic 5: Complex Situations in Opioid Prescribing.
Prescription Drug Monitoring Programs
PDMPs are online systems of searchable information about controlled-substance pre-
scription fills, including the location and date of the fill, the names of the prescriber
and recipient, and the dose and quantity of medications.

States vary in whether they require clinicians to consult PDMPs before prescribing and
at what interval. In addition, some states require reporting of buprenorphine for treat-
ment of opioid use disorder (OUD) within an opioid treatment program and some do
not; methadone used in an opioid treatment program is not reported to PDMPs.

Information of potential concern in a PDMP report may include:

• Multiple concurrent opioid prescriptions

• Prescriptions from different prescribers
• Early refills
• Potentially dangerous drug combinations (e.g., involving opioids,
benzodiazepines, stimulants, and muscle relaxants)
• Filling of opioid prescriptions at unexpected or multiple pharmacies
• Payment for opioid prescriptions with cash rather than through insurance
coverage (if insured)
Next Steps Following Signs of Potential Misuse
When worrisome behavior is noted, clinicians sometimes respond by abruptly discon-
tinuing opioids for that patient, but this may in turn be associated with a transition to
illicit opioids and an increased risk of overdose. Therefore, it is preferable to discuss
findings suggestive of misuse with the patient and, if concerns persist, with other care
providers or significant others who may be able to shed light on the concerns.

The clinician should also assess whether the patient has OUD. The care plan should
be revised as appropriate to both meet the patient’s clinical needs and assure safety; if
OUD is diagnosed, this may include offering or facilitating appropriate treatment and
tapering of opioids.

TAPERING OF OPIOIDS
Tapering of opioids allows a patient to either stop the opioid altogether or to continue
it but at a lower dose. In a patient with physical dependence on opioids, any reduction
in the opioid dose should be done gradually, with a slow taper, to avoid withdrawal
symptoms.

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When to Consider a Taper
Tapering may be considered for a variety of reasons:

• Lack of adequate benefit

– Declining function despite pain control
• Presence of opioid-related harms
– Evolution of medical comorbidities that increase opioid-related risks
– Persistent adverse effects from the opioid
– Worrisome opioid-related behaviors; these patients should be assessed for
OUD and considered for transition to opioid agonist treatment for OUD
• Patient desire for a trial off opioids
• Resolution of pain but persistent physical dependence on the opioid
• To determine if a patient with good pain control on stable opioid doses still
requires the opioid
• Suspicion of opioid-induced hyperalgesia
• Unrelenting opioid tolerance without resolution on rotation

Note that many of the reasons to consider a taper of opioids are the same as those for
which clinicians may consider rotation of opioids (i.e., presence of adverse effects or
lack of adequate benefit); thus, clinical judgment must be used to determine the best
course of action for an individual patient. Sometimes initial tapering is appropriate,
but then rotation becomes necessary if elimination of opioids is not successful due to
recurrent pain that is not controlled with other means.
Approaches to Tapering
The best approach to opioid tapering depends on many variables, including the reason
for the taper (i.e., possible harm vs. lack of adequate benefit), opioid doses used, dura-
tion of opioid use, type of pain, and patient preferences.

The ideal taper allows time for the body to adjust to

declining doses of opioid and thus avoid signs and SIGNS AND SYMPTOMS OF
symptoms of withdrawal, which can be associated WITHDRAWAL:
with increased pain and inability to continue the taper
• Increased heart rate
(see box).
• Increased pupil size
Although withdrawal is most common when there is a • Yawning
sudden, >25% drop in the opioid dose, its occurrence • Rhinorrhea or tears in the eyes
is highly variable. In clinical practice, a taper of 10% • Sweating
per month is often used for patients who have been • Restlessness
taking opioid therapy long-term (for many years) for • Arthralgia
chronic pain; a taper of 10% per week is used for • Gastrointestinal disturbances
patients who have been taking opioids for weeks to • Tremor
months. This pacing is consistent with recommenda- • Irritability or anxiety
tions from the U.S. Centers for Disease Control and • Piloerection
Prevention and is generally well tolerated by patients.

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In some cases, withdrawal symptoms still occur, and these are often managed with an
alpha2-adrenergic agonist such as lofexidine, clonidine, or tizanidine.

If a more rapid taper is necessary, many patients appear to tolerate an initial reduction
of 20%, followed every 3 to 5 days by a reduction of 10% to 20% of the remaining dose.
Whatever taper schedule is planned, revision should be made as indicated based on
patient response.

Ultra-rapid tapers have been described, some using sedation or anesthesia, but stud-
ies do not support long-term advantages of these tapers compared with more-gradual
tapers, and they engender both risks of withdrawal and complications of sedation when
used.

Of note, tapers are not necessary when diversion is identified by a non–physically depen-
dent person.
Tapering During Pregnancy
Tapering of opioids is generally best avoided during pregnancy given the risk of preg-
nancy loss; however, if tapering must be pursued, the risk of pregnancy loss is lowest
in the second trimester.
Pain Management During a Taper
Some patients with chronic pain may experience a reduction in pain as opioids are
tapered (presumably due to lessening of opioid-induced hyperalgesia); however, many
patients require intensified pain management with nonopioid therapies while tapering.
Approaches may include:

• Physical approaches, such as exercise, physical therapy, massage, thermal

modalities, and movement therapies (yoga, qi gong, stretching)
• Psychological interventions, such as mindfulness, meditation, and therapies such
as cognitive behavioral therapy, acceptance and commitment, and dialectical
behavioral therapies as indicated
• Nonopioid medications as indicated, including acetaminophen or nonsteroidal
anti­inflammatory drugs, SNRIs or tricyclic antibiotics, anticonvulsants, or muscle
relaxants such as tizanidine
• Carefully targeted interventionalist procedures

TOOLS FOR CLINICAL PRACTICE

Assessing Depression and Anxiety
• Patient Health Questionnaire (PHQ)-2: A 2-item questionnaire used to screen for
depression; to be followed by the PHQ-9 if positive
• Generalized Anxiety Disorder (GAD)-2: A 2-item questionnaire used to screen for
anxiety

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Assessing Withdrawal
• Clinical Opiate Withdrawal Scale (COWS): An 11-item scale scoring the
frequency and severity of withdrawal symptoms
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 Taper Decision Tool: A 3-page guide from the U.S. Department of
Veterans Affairs that outlines sample taper plans and treatments for specific
withdrawal symptoms
• BRAVO! A Collaborative Approach to Opioid Tapering: A 15-page document
(from Oregon Pain Guidance and Dr. Anna Lembke) outlining a safe and
compassionate strategy to approaching opioid tapering with patients
• BRAVO Overview: A one-page overview of the BRAVO approach to opioid
tapering
• DSM-5 OUD Criteria: A complete list of diagnostic criteria for opioid use
disorder

Last reviewed Mar 2020. Last modified Mar 2020. 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.

© 2020 Massachusetts Medical Society. All rights reserved.

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