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CDC Guidelines for Prescribing Opioids for Chronic Pain

2 Contact Hours - 2 Pharmacology Hours
This course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Registered Nurse (RN)
This course will be updated or discontinued on or before Tuesday, February 1, 2022
Course Description
This course is meant to provide two contact hours to meet the State of Iowa’s continuing education requirement based on the Centers for Disease Control and Prevention guidelines for prescribing opioids for chronic pain.
CEUFast Inc. did not endorse any product, or receive any commercial support or sponsorship for this course. The Planning Committee and Authors do not have any conflict of interest.

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To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
  2. Reflect on practice impact by completing self-reflection, self-assessment and course evaluation.
    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Raymond Lengel (MSN, FNP-BC, RN)

Outcomes

This course is meant to provide two contact hours to meet the State of Iowa’s continuing education requirement based on the Centers for Disease Control and Prevention guidelines for prescribing opioids for chronic pain.

Objectives

After completing this course, the participant will be able to meet the following objectives:

  1. Compare and contrast acute versus chronic pain.
  2. Discuss the Center for Disease Control and Prevention’s guideline for prescribing opiates.
  3. Discuss recommendations on limitations on dosages and the length of prescriptions for opiates.
  4. List five risk factors for opiate abuse and misuse.
  5. Discuss treatment options for chronic pain including opioids, nonopioids, and nonpharmacologic therapy options.
  6. List ten steps to safe and effective prescribing control substances including opiates.

Overview

The Iowa Administrative Code (IAC) 655, chapter 7, sets out certain standards for controlled substances regarding the advanced registered nurse practitioner (ARNP)1. According to the IAC, two contact hours of continuing education should be completed by the ARNP regarding the Center for Disease Control and Prevention guidelines2 for prescribing opioids for chronic pain every three years.

IAC 655 chapter 7.6 discusses eight key points regarding the standards of practice for ARNPs surrounding controlled substances.1 First, the health history taken by the provider should assess for a personal and family history of substance abuse risk. If this assessment does not occur, the provider should document the reason the assessment was not performed. Second, the assessment should also include written documentation of at least one indication for using a controlled substance. Third, the ARNP should use a treatment agreement if they continue to prescribe at least one controlled substance.

Fourth, while prescribing a controlled substance, the ARNP should educate and document this education to include, at minimum, the risks of the medication and information regarding tolerance, abuse, physical dependence, and addiction. If education not provided, the ARNP must document the reason. Fifth, the ARNP must maintain an active Drug Enforcement Administration registration and an active-controlled substance Act registration to prescribe, administer, or dispense controlled substances.

Sixth, the ARNP should generally not prescribe controlled substances to oneself or any family members. The only exception to this is if there is an emergency, and there are no other qualified providers available. Seventh, the ARNP may be disciplined if found opioids prescribed in dosages that would not be prescribed by another reasonably prudent ARNP in a similar practice.

Eighth, the ARNP who prescribes opioids must complete a minimum of two contact hours of continuing education about prescribing opioids based on the Center for Disease Control and Prevention’s guidelines for prescribing opioids for chronic pain.

Also, IAC 655, chapter 7.71, states that the ARNP should utilize the prescription monitoring program before prescribing or dispensing an opioid. The exceptions to this rule include when treating a patient who is getting inpatient hospice services or those in long-term residential care. It also does not apply to the ARNP who issues a medication order for an opioid to be given in a clinic or hospital, as the ARNP is not dispensing or prescribing.

Introduction

In 2016, the Center for Disease Control (CDC) published a guideline for prescribing opioids in those with chronic pain who are not active cancer patients, end-of-life care patients, or palliative care patients.

This guideline serves to provide recommendations to the primary care provider. It specifically looks at when to start and or continue to use opioids for chronic pain. It discusses dosage, drug selection, follow up, and when to stop the medication. It also looks at assessing the risks and harms of opioid therapy.2

Prescription opioid abuse takes a heavy toll on the patient, healthcare provider, and society. Abuse and misuse of controlled substances occur for multiple reasons, including self-medication, use for reward, diversion for-profit, and compulsive use. Opioid use has increased in recent times leading to an increase in abuse and opioid overdoses. Proper screening lowers the risk of iatrogenic addiction. Unfortunately, no currently available screening method accurately predicts who is at high risk of abuse or misuse opiates.3

Using prescribed medications, not as directed, describes potentially aberrant drug-taking behaviors. In a study of 202 patients, only 44.1% were screened for potential aberrant drug-taking behaviors. The study concluded that screening for abuse or misuse of opioids does not frequently occur in large family medicine training programs. More training and set policies for risk evaluation and monitoring for opioid abuse are needed.4

Health care providers tend to misdiagnose patients at risk for opioid-related aberrant behaviors. One study showed that providers assessed the risk of misuse, abuse or diversion at less than 2%, when in reality, 10.4% of patients had prior illicit drug use, 23.4% and abnormal urine drug tests, almost 11% reported crushing or chewing opioids in the past and 60% of patients self-reported abuse, misuse or diversion.5

Prescriber lack of training and inexperience can have a profound impact on the misuse of medications. One study showed that resident physicians (when compared to attending physicians) more often prescribed opioids for more than three months, were more likely to have their patients report that their prescriptions were lost/stolen, were more likely to have patients who exhibited substance misuse and were more likely to have their patients get opioids prescribed by a different prescriber in addition to them.6

Prescribers receive little training in how to prescribe scheduled substances, how to screen for substance abuse, and how to refer patients who need treatment for substance abuse. Proper continuing education is one way to address this problem.7

Opiate Abuse and Misuse

Opioids have the potential to provide analgesia and improve function. These benefits must be weighed against the potential risks, including misuse, addiction, physical dependence, tolerance, overdose, abuse by others, drug-to-drug, and drug-to-disease interactions.

Prevalence

  • In 2016, 48.5 million individuals in the United States misused prescription drugs or used illicit drugs. Sixty-six percent of the 630,000 drug overdose deaths were due to illicit or prescription opioids. The number of opioid overdoses to the emergency department increased by 30 percent from July 2016 to September 2017.8
  • Opioid misuse affects 34.2 million Americans over the age of 12.9 According to the Center for Disease Control and Prevention (CDC), 46 people die each day in the United States from an overdose of prescription painkillers.
  • In 2012, healthcare providers wrote 259 million prescriptions for painkillers.10 Two times as many painkiller prescriptions are written in the United States as in Canada.
  • Overdoses from synthetic opioids increased from 3.1 per 100,000 people in 2015 to 6.2 people per 100,000 people in 2016.11
  • Between the years of 1999 and 2015, drug overdose deaths have tripled.12
  • 12.2% of 12th graders reported ever abusing opioids, and 7.9% reported past-year use.13
  • The number of individuals who sought treatment for non-heroin opioid substance abuse increased from 1.0% in 1995 to 8.7% in 2010.14
  • Of overdose deaths from opioid analgesia, 30% also involved benzodiazepines.15

Opioid dependence costs the United States health care system one billion dollars annually.16 In addition, opioid dependence leads to decreased work productivity, increased legal costs, and lasting psychological effects experienced by the victims of the crimes caused by opioid abuse. Opioid misuse may lead to other diseases such as HIV, hepatitis, and sexually transmitted diseases.

Pain

Definitions

  • Pain – “An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”
  • Acute pain – Pain that has an abrupt onset and offers a warning of a disease process or a threat to the body.
  • Chronic pain – Pain that lasts beyond the usual duration of time that an insult or injury to the body needs to heal (typically at least three months). Chronic pain is without apparent biologic value. Some define chronic pain as pain that continues for at least six months.17
  • Maladaptive pain – Pain that is not useful and is out of proportion to tissue damage. This type of pain tends to last long after tissue healing and is often due to changes in the central nervous system.
  • Adaptive pain – Pain that protects the individual from injury and aids with healing after an injury.
  • Allodynia — Pain from a stimulus that typically does not cause pain.
  • Hyperesthesia – Increased sensitivity to stimulation.
  • Paresthesia — An unusual sensation that is often described as burning or prickling and commonly affects the extremities.
  • Visceral pain – Pain from the viscera mediated by stretch receptors. This pain is commonly described as deep, dull, poorly localized, and cramping.
  • Nociceptive pain – Pain from threatened or real tissue damage to non-neural tissue that is caused by the activation of nociceptors.
  • Neuropathic pain – Pain from an abnormal neural activity from an injury, disease process, or dysfunction of the nervous system.
  • Mononeuropathy – A Neuropathy affecting one nerve.
  • Polyneuropathy – A Neuropathy affecting several nerves.

Acute Pain

Acute pain is defined as, “Pain that has an abrupt onset and offers a warning of a disease process or a threat to the body.”28 Management of acute pain may include opioids. While good pain control is important in patient care, the use of opioids for acute pain increases the risk of long-term opioid use. Use of caution is imperative because long-term opioid use often begins with the treatment of acute, self-limiting afflictions. Ideally, opioids should be prescribed only when necessary, with the lowest effective dose and for the shortest duration possible.

Acute painful conditions may include post-operative pain and other conditions commonly encountered in the primary care setting or emergency department. Recent guidelines have considered this and have re-examined the best way to manage acute pain.

The Center for Disease Control suggests that opioids should only be used when necessary and at the lowest effective dose. Less than three days of opioid medication is appropriate for nontraumatic nonsurgical pain.19 Immediate-release opioids are recommended for short term use, although in some instances of acute pain may require more than three days.

New York City published guidelines for the use of opioids. They recommend that most patients require three or fewer days of therapy, giving patients short-acting medication, patients should be evaluated for addiction or misuse, avoid administered benzodiazepines and opiates together, and use extreme caution with stolen, lost, or destroyed prescriptions.20

When too many pills are prescribed, there are “left-over pills.” These left-over pills may have use for diversion or abuse. Nonetheless, it is often difficult to predict how much acute pain each patient will have and how many pills to prescribe.

One study showed that persistent opioid use occurred after surgery between 5.9 and 6.5% of the time.21 Some factors increase the risk of persistent opioid use. These risks include the history of alcohol or drug abuse, lower socioeconomic status, multiple medical comorbidities, depression, use of benzodiazepines or antidepressants, and preoperative pain.

Chronic Pain

Chronic pain affects approximately 76.2 million Americans.22 Pain is a common problem seen in primary care, with about 20% of outpatient visits being for pain issues. Chronic pain affects about one in two long-term care residents.24

Persistent pain is often associated with anxiety, depression, functional impairment, sleep disturbances, disability, and impairment in activities of daily living. Every year, chronic pain leads to more than 50 million lost workdays in the United States and costs the American taxpayer over 100 billion dollars.25

Chronic pain is defined as pain lasting more than three months and may affect any part of the body. Chronic pain is most frequently caused by back pain (10%), leg/foot pain (7%), arm/hand pain (4.1%), headache (3.5%), and widespread pain (3.6%). Many individuals affected by chronic pain have more than one type of pain.26

The definition reads, “An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”27

The definition of chronic reads, “Pain that lasts beyond the usual duration of time that an insult or injury to the body needs to heal.”28 Chronic pain can also be viewed as pain without apparent biologic value that has lasted beyond the usual tissue healing time (typically at least three months). Some define chronic pain as pain that continues for at least six months.27

An expert panel concluded that chronic opioid therapy might be effective for some individuals with chronic non-cancer pain that have been thoughtfully selected.28 The use of high dose long-acting opioids are used only in specific circumstances with severe, intractable pain that has not responded to short-acting or moderate doses of long-acting opioids. No evidence exists as to who responds better between long-acting and short-acting opioids concerning pain relief and side effects.29

A recent survey showed that individuals might go to extreme lengths to obtain certain prescription medications. Opioids were the most obtained medications, followed by the sedative-hypnotics and amphetamines. Individuals who seek these medications are more likely to use more than one physician and more than one pharmacy. This survey showed that seventy-five patients feigned symptoms to get prescriptions, two of thirty-six used falsified MRI images, three patients paid the prescribers, and three harmed themselves to get the prescriptions.30

Management of Acute and Chronic Pain with Opioids

A comprehensive medical history is the first step in the workup of an individual experiencing pain. Many healthcare providers believe pain is the fifth vital sign. A comprehensive medical history should include an evaluation of the patient’s medical and surgical history and a review of the medication list.

The comprehensive medical history must include a detailed description of the pain. The pneumonic: OLD CARTS has been used to evaluate pain.

  • Onset
    • When did the pain start?
    • Describe the mechanism of injury?
    • What was the causative factor?
  • Location
    • Where is the pain?
  • Duration
    • How long has the pain persisted?
    • Is the pain intermittent or constant?
  • Characteristics
    • Describe the pain (dull, sharp, lancing, burning, throbbing, or squeezing).
  • Associated symptoms
    • Are there any other symptoms associated with the pain such as spasms, reduced range of motion, edema, diaphoresis, weakness, or changes in skin, nails, or hair?
  • Radiation
    • Does the pain radiate? If so, where?
  • Temporal
    • What are the aggravating/causative factors?
    • What factors alleviate or diminish pain?
  • Severity
    • Rate the severity of the pain?

Document the impact the pain is having on the patient’s quality of life. Ask:

  • Does the pain affect activities of daily living or instrumental activities of daily living?
  • Does the pain limit exercise or activity?
  • Does the pain affect your mood?
  • Is there a reduction in your energy?
  • Does the pain lead to a strain on relationships?
  • Does the pain affect your sleep?
  • Does the pain lead to mood alterations?
  • Does the pain affect your social life?

Measuring the intensity of pain is often done on scales to compare the intensity of the patient’s pain at different points in time, not to compare one person’s pain to another. The use of pain scales helps the prescriber assess the effectiveness of pain treatment.

The best scales are brief, valid, require minimal training to use, and use both behavioral and descriptive measures of pain.25 A scale commonly used rates pain from 0 to 10. Another scale allows the patient to rate their pain as no pain, mild pain, moderate pain, severe pain, or unbearable pain. Other scales have the patient select the degree of pain on a pictorial scale with facial expressions. Pain maps are helpful in individuals who have a difficult time speaking. Pain maps have a front and rear view of the body on a piece of paper, and the patient marks the location of the pain and rates the severity of the pain.

Review the patient’s perception of the pain:

  • What is the patient’s treatment goals?
  • Why does the patient think they have persistent pain?
  • Does the patient feel there was enough workup done on their condition?

Assess the psychological factors that contribute to the pain. Patients need to have reasonable expectations about the pain and its management.

All patients with chronic pain should have a complete physical examination. It is important to have a baseline physical examination, so ensuing evaluations will permit the healthcare team to establish progress in the pain management plan.

Other key features assessed before treatment include:

  • Current and past treatments
  • History of substance abuse
  • Underlying conditions

The physical examination should include:

  • Hygiene, dress, and appearance - those in severe pain will often have poor hygiene and be unkempt
  • A detailed neurological examination
  • Assessment of skin and joints for redness, swelling or deformities which may help determine the location and etiology of pain
  • Assessing for joint range of motion
  • Inspecting for any splinting
  • Looking for signs of chronic liver disease
  • Performing an abdominal examination for any tenderness, mass or distention
  • Performing a skin examination that looks for any track marks
  • Evaluating for any signs of acute intoxication, withdrawal signs, or over sedation
  • Assess for infection, particularly among individuals administering by self-injection
  • Looking for a productive cough, as there is a high rate of tuberculosis and community-acquired pneumonia
  • Assessing for respiratory problems, from smoking or snorting substances
  • Evaluation for a sudden exacerbation of a previously well-controlled disease state, such as hypertension or diabetes
  • Looking for unexplained weight loss
  • Assessing for sleep disturbances

Goals of Treatment

An important role of the practitioner is prescribing controlled substances. Establishing treatment goals is an important aspect of opioid therapy. Goals should focus on pain relief and improvement in functioning. Prescribing controlled substances is laced with risks, and it is important for the prescriber to realize that a primary goal of prescribing opioids should be to maintain patient safety. A responsible prescriber should follow multiple steps to ensure the safe and effective care of their patients.

Therapeutic goals should be established regarding pain control and improvement in function. Pain goals typically involve a reduction in pain, not necessarily an elimination of pain. Functional goals may include improved sleeping, increased ability to perform activities of daily living, progress in physical therapy, increased social interactions, returning to work, and improved regular exercise. In addition, goals should also include limiting side effects and minimizing adverse drug events.

Treatment of Pain

Pain typically classifies as nociceptive, neuropathic, or other. Nociceptive pain comes from tissue damage or inflammation and may originate from the muscles, joints, skin, organs, bones, or tendons. It may include burns, tumors, muscle strain, joint pain, arthritic pain, or post-surgical pain.

Neuropathic pain comes from damage to the nervous system. It may result from anything that damages neurons. The damage may include pinching of the sciatic nerve, damage from chemotherapy, phantom limb pain, multiple sclerosis, diabetic neuropathy, postherpetic neuralgia, or post-stroke central pain. This pain usually describes as burning, tingling, stabbing, or electrical. The pain type of neuropathic pain is more likely to lead to chronic pain as nerves do not heal as well.

Examples of other pain that cannot classify into these two categories include fibromyalgia, complex regional pain syndrome, or nonspecific chronic low back pain.

The management of pain may include medications, behavioral interventions, physical medicine, neuromodulation, medical interventions, or surgery. The use of a multidisciplinary approach is typically used in the management of chronic pain.

Non-pharmacological therapy

Numerous non-pharmacologic therapies have use in the management of pain. Methods used other than medications include physical therapy, exercise, massage, ultrasound therapy, heat/cold application, chiropractic manipulation, biofeedback, psychotherapy, relaxation therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS), injections, neuromodulation, spinal cord stimulation, deep brain stimulation, and radiofrequency ablation of nerve tissue.

Pharmacologic Interventions

The World Health Organization (WHO) analgesic ladder was created for the management of cancer pain and published in the 1980s.31 Key points of the analgesic ladder include:

  1. Medications are given through the most comfortable route (preferably orally).
  2. A stepwise approach should start with non-opioid medications with or without adjuvant medications.
  3. Managing mild to moderate enduring or progressive pain with opioids, with or without adjuvant medications, with or without non-opioids.
  4. Considering the use of more potent opioids such as morphine with or without adjuvant medications with or without non-opioids for persistent pain or pain that is increasing, notwithstanding the previous step 3 above.
  5. Administering analgesic pain medication used for moderate to severe chronic pain on a fixed schedule (not as needed).

This approach is 80-90 percent effective.

What are adjunctive medications? Adjunctive medications are medications used to enhance the analgesic effect, reduce side effects, and assist with co-existent symptoms. Different patients will respond distinctively to different treatments regarding efficacy and side effects. Trial and error are often used in the treatment of chronic pain.

When starting therapy for chronic pain, the dose should be initiated at a low dose and titrated to obtain pain control and minimize side effects. Tolerance often develops as a patient gets used to the medication.

Classes of medications include non-opioid analgesic agents, antidepressants, muscle relaxants, antiepileptic medications, topical agents, and opioids. Some get effective relief from one medication, but some get better pain relief from a combination of medications that work on different pathways. Unfortunately, research is sparse on combination medication in the management of pain.

While the patient is under treatment for the pain, the clinician should assess and document the effect on functional status, pain control, the intensity of pain, and side effects.

Analgesic agents are often given orally as this is convenient and allows a relatively steady blood concentration of the drug. Pain medication may be administered on an as-needed basis for episodic pain, or it may be given routinely for chronic pain. The use of routine, around-the-clock medication sustains a steady state in the blood and offers better pain relief for those with persistent pain.

Considering all co-morbidities is an important step in the management of pain. For example, when a patient suffers from chronic pain and depression, some medications may help effectively manage both conditions (for example, duloxetine is approved to treat chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain in addition to depression). It is also important to establish the pathophysiology of the pain syndrome, evaluate the medication list, and consider the side effects of the medications prescribed.

The clinician should distinguish between neuropathic pain and nociceptive pain. The etiology of neuropathic pain must be established, and if the etiology is reversible, manage the underlying problem. For example, if a medication (e. g., metronidazole, nitrofurantoin, isoniazid, or many cancer agents) is the etiology of the neuropathy – stop that medication.

Medications used in the treatment of neuropathic pain include calcium channel alpha 2-delta ligands (gabapentin and pregabalin), tricyclic antidepressants, serotonin-norepinephrine uptake inhibitors (SNRIs), the lidocaine patch, and narcotic analgesics.

Nociceptive pain is typically treated with non-narcotic and opioid analgesia. Acetaminophen is often used as a first-line agent in the management of nociceptive pain. Doses can be hepatotoxic at doses greater than three to four grams a day. Non-steroidal anti-inflammatory agents (NSAIDs), which are more effective than acetaminophen, are used as alternative options to acetaminophen and are indicated for mild to moderate pain, while some for severe pain. Like acetaminophen, they act synergistically with opioids.

Opioids

NSAIDs present with risks, and some patients are unable to tolerate NSAIDs due to side effects and co-morbid conditions. The risk associated with NSAIDs is one reason many clinicians choose an opioid to manage pain. Opioid therapy is effective in the management of many chronic pain conditions, including osteoarthritis, low back pain, neuropathic pain, and postherpetic neuralgia.

A position paper from the American Academy of Neurology suggested that there is evidence for good short-term pain relief with opioids, but no good evidence exists for continuation of pain relief or improved function for extended periods without sustaining serious risk of dependence, overdose, or addiction.32

When non-opioid therapy is ineffective, or there is severe nociceptive pain, opioid therapy may be considered. In chronic back pain, opioids do not improve pain scores any more than non-opioid therapy.33 Opioid therapy is often used to manage neuropathic pain but is thought to be the second line to antidepressants and anticonvulsants. The recommendations section below will provide guidelines on the proper use of opioid medications.

When opioids are used for chronic pain, treatment is typically started with short-acting medication, and the medication titrated upwards to control pain while side effects monitored. After determining the dose of the medication required to provide adequate pain relief with minimal side effects, the medication can then be converted to a sustained release form with administration once or twice a day. When long-acting medication in use, breakthrough medication can be given.

Side Effects

Opioid medications are associated with multiple side effects, including constipation, nausea, vomiting, pruritus, abdominal cramping, sedation, and mental status changes. Multiple interventions are available to reduce side effects.

  • Constipation is a frequent issue in those who use opioids. Risk factors for constipation include older age, those with intra-abdominal pathology, and those who eat a low fiber diet. Those on opiates should be encouraged to increase fiber intake, drink plenty of fluids, and be encouraged to exercise. Stool softeners (e.g., docusate sodium) and stimulants (e.g., bisacodyl) may be needed to manage constipation. An osmotic laxative such as polyethylene glycol or lactulose may also be considered, which may be added to stools softeners/stimulants for resistant constipation.
  • Antiemetic medication can help treat nausea.
  • Antihistamines can treat pruritus.
  • Opioids are associated with somnolence and other mental status changes. Patients do develop tolerance to these symptoms over weeks. Reducing the dose may lessen the mental status changes. An adjunctive medication may allow a lower dose of opioids to manage the pain. Rarely, the use of a stimulant is used to manage sedation due to opioid use.
  • Respiratory depression may occur, but it is uncommon when opioids used carefully. Starting low and slowly titrating the dose will reduce the risk of respiratory depression. Problems arise with rapid titration, the addition of another drug that may suppress the respiratory drive (benzodiazepine, alcohol, or a barbiturate) or the patient overdoses. Sedation precedes respiratory depression, so when starting a patient on opioid therapy, encourage them to take the first dose in the office to be monitored or in the presence of a responsible adult who can help monitor the patient. The level of consciousness should be assessed 30-60 minutes after the opioid given. The next dose should be held, and the prescriber should be contacted immediately if there is a reduced level of consciousness, hypoxia occurs, or the patient has a respiratory rate of less than 10 per minute.25

Individual Medications

Table 1: Key Terms
  • Opioid naïve - those who have not had opioids in the last 30 days
  • Opioid tolerant - someone who has taken 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids for at minimum one week.34

Morphine

While there are many opioids, morphine is considered by many as a standard comparator for other drugs. Morphine can be given orally, rectally, intravenously, subcutaneously, or intramuscularly.

Morphine has a use for moderate to severe acute pain and chronic severe pain. It comes in multiple formulations. For acute pain, its oral and rectal formulation is dosed at 5-30 mg every 4 hours. It is available as a tablet, solution, suppository, and parenteral solution. Morphine also comes in a controlled release form, a sustained-release form, and an extended-release form.

Longer-acting formulations include:

Arymo ER and MorphaBond ER are extended-release tablets. The initial dose is 15 mg every 8 to 12 hours in those who are not opioid-tolerant or as the first opioid used. It can be titrated every 1-2 days.

Do not give Kadian for initial opioid analgesia. For non-opioid tolerant patients, 10-30 mg once a day is recommended. Higher doses are indicted for opioid-tolerant patients. Titration may be done every 1- 2 days. When converting from other forms of morphine, it may be given once or twice a day.

MS Contin is started at 15 mg every 8-12 hours, with the dosage adjusted every 1-2 days.

Morphine should not be used in those with a hypersensitivity to morphine, those with toxin-mediated diarrheal disease, and those with severe/acute asthma, paralytic ileus, or severe respiratory depression. The extended-release form should not be used in those with GI obstruction.

The extended-release forms of morphine are not interchangeable. Changing from one medication to another should be done only by those experienced in how to do this. Extreme caution should be used when using a highly concentrated solution, so overdoses do not occur.

Fentanyl

Fentanyl can be given as an injection, transdermal patch (Duragesic®), an oral transmucosal lozenge (Actiq®), a sublingual tablet (Abstral®), a sublingual spray (Subsys®), a buccal tablet (Fentora®), a buccal film (Onsolis®) and a nasal spray (Lazanda®). The transdermal patch is used in opioid-tolerant patients with moderate to severe pain and is often started at 25 mcg per hour and changed every 72 hours.

Fentanyl can be used for multiple reasons, including premedication for surgery, general anesthesia, as an adjunct to general and regional anesthesia, and chronic pain management. The transdermal patch is indicated for around the clock pain management in those with chronic severe pain. Fentanyl transmucosal and intranasal is indicated for cancer pain.

While no official dosage adjustment recommendations exist with those with renal or hepatic impairment, those with mild to moderate renal or hepatic impairment should likely have the dose reduced by 50 percent with the patch with fentanyl use not recommended in severe renal or hepatic impairment. Transmucosal and nasal spray have no specific recommendations for dose reduction in renal or hepatic impairment.

As with most opioids, contraindications include hypersensitivity, toxin-mediated diarrheal disease, and paralytic ileus. It should not be used for short-term pain, post-operative pain, or for those who have severe respiratory disease. The transmucosal and nasal form of fentanyl are typically only used by specialists for opioid-tolerant cancer patients.

The patch form should not be exposed to external heat, as this may increase the absorption of the medication. Also, patients with a fever may notice an increase in the absorption of the medication. The patch should only be applied to intact skin, and it contains aluminum and must be removed before an MRI.

Oxycodone

Oxycodone is a schedule II-controlled substance and is available in multiple forms.

  • Immediate release is dosed 5-20 mg every 4-6 hours (lower range for opioid-naive patients).
  • The controlled release tablet is indicated for those who require around the clock pain control. It is dosed 10 mg every 12 hours to start and titrated carefully. There is also an extended-release capsule, which is started at 9 mg every 12 hours.
  • It also comes as an oral concentrate and oral solution.
  • Oxycodone is often combined with other analgesic agents such as acetaminophen, aspirin, and ibuprofen.

Those with a creatinine clearance less than 60 mL/min should have the dose adjusted down as serum concentration of oxycodone will increase in renal insufficiency. Those with hepatic impairment should have doses reduced. The starting dose should be lowered one-third to one-half and slowly titrated up to effect.

Oxycodone is contraindicated in those with paralytic ileus, significant respiratory depression, hypercarbia, acute or severe bronchial asthma, and GI obstruction.

Caution should be used in those with biliary tract impairment, such as acute pancreatitis, as it may lead to constriction of the sphincter of Oddi. It may lead to an elevation of intracranial pressure (ICP) and should be used carefully for those with intracranial lesions, elevated ICP, or a head injury.

Hydrocodone

Hydrocodone, classified as a Schedule II Controlled Substance in October of 2014, is available as a combination pill with a non-narcotic analgesic and by itself in an extended-release form. The combination pill has a short-acting version of hydrocodone and is dosed 2.5 to 10 mg of hydrocodone every 4-6 hours as needed for moderate to severe pain.

Hydrocodone extended-release (Zohydro ER®) is typically dosed 10 mg every 12 hours in opioid-naive patients. It is used for severe pain requiring around the clock dosing of hydrocodone. The dose may be increased every 3-7 days in 10 mg increments. Hysingla ER® is dosed 20 mg once a day while increased the dose of 10-20 mg every three to five days. Vantrela ER® is also available and is initially dosed at 15 mg every 12 hours.

Those with severe hepatic impairment should start at the lowest dose and titrate up very slowly while monitoring for side effects. Caution should be used with renal impairment as plasma concentration may rise.

Contraindications to hydrocodone include paralytic ileus, severe asthma, severe respiratory depression, and hypercarbia.

Tramadol

As of August 18, 2014, the DEA placed tramadol into a Schedule IV of the Controlled Substance Act. It is indicated for chronic moderate-to-severe pain. For those who do not need a rapid onset of pain relief nor affected by side effects, it may be dosed at 25 mg/day and titrated up every three days to 50-100 mg every 4-6 hours to a maximum of 400 mg a day.

Tramadol also comes in an extended-release form, which is dosed 100 mg once a day and titrated by 100 mg every five days to a maximum dose of 300 mg a day.

When prescribing tramadol to older adults, use the lower end of the dosage range and titrate slowly. In those over 75 years old, 300 mg a day should not be exceeded and utilize extreme caution with the extended-release form.

In those with a creatinine clearance less than 30 mL/min, only the immediate release formulation should be used with doses of 25-100 mg split every 12 hours (maximum dose of 200 mg a day). In those with severe liver impairment, the immediate release form should not exceed a maximum of 50 mg every 12 hours.

Patients may experience withdrawal symptoms from tramadol that may include nausea, diarrhea, anxiety, pain, sweating, tremor, and rigors. Extended use of tramadol may lead to dependence, and these medications should be tapered slowly to reduce the risk of withdrawal symptoms.

Evidence shows tramadol may increase the risk of seizures. This risk increases in those who take serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, other opioids, or other drugs that lower the seizure threshold. The risk may also increase in those who have seizures or are at risk for seizures, such as those who have a CNS infection, cancer, history of head trauma, or while patients are going through drug or alcohol withdrawal.

Other Medications

Oxymorphone, a schedule II medication, can be given intravenously, subcutaneously, intramuscularly or orally. For acute pain, the immediate-release tablet (Opana®) is used at 5-20 mg every 4-6 hours as needed for opioid naïve patients. For those with chronic severe pain, the extended-release tablet is used (Opana ER®) and is started at 5 mg every 12 hours and may be titrated up at 5-10 mg increments every three to seven days. Caution should be used in those with a creatinine clearance less than 50 mL/minute, and the medication should not be used in moderate to severe hepatic impairment.

Hydromorphone can be given orally, rectally, subcutaneously, intramuscularly, or intravenously. The oral medication comes in standard and extended-release forms. The standard form is used for moderate to severe pain and is often dosed 2 to 4 mg tablets every 4-6 hours. The oral liquid is typically dosed 2.5 to 10 mg every 3 to 6 hours. Parental and oral doses are not equivalent. The parenteral dose is five times more potent than the oral dose. The long-acting form (Exalgo®) is used for opioid-tolerant patients who have chronic severe pain. It is dosed 8-64 mg once a day.

Methadone can be given intravenously, subcutaneously, intramuscularly, or orally. The oral dose is started in the opioid naïve patient at 2.5 every 8-12 hours. Methadone is a high-risk drug that can lead to overdose. It has a half-life of up to five days and may accumulate in the body. Methadone may also prolong the QT interval leading to cardiac arrhythmias, especially at doses higher than 120 mg a day. Methadone should be used for severe pain that has not been responsive to other agents and only by clinicians with specific training in the use of methadone. Methadone has use in the detoxification process.

Tapentadol (Nucynta®, Nucynta ER®) is used for acute moderate to severe pain and started at 50-100 mg every six hours for the immediate-release formulation. The starting dose for the extended-release tablet is 50 mg every 12 hours. For chronic pain, it is typically dosed 100-250 mg two times a day as needed. This medication is not recommended for those with severe liver or renal insufficiency. It is also indicated for diabetic peripheral neuropathy.

Propoxyphene has been taken off the US market due to a connection with fatal cardiac arrhythmias. Meperidine is not recommended as a first-line agent for chronic pain as it is associated with high rates of central nervous system toxicity.

U.S. Centers for Disease Control and Prevention Guideline for Prescribing Opioids

The Center for Disease Control (CDC) and Prevention developed guidelines for prescribing opioids in chronic pain. It offers guidance to the clinician regarding safe and effective prescribing of opioids and assistance in the management of chronic pain. This guideline focuses on patients over the age of 18 who seen in the primary care setting. The guideline focuses on chronic pain that does not involve end-of-life care, active cancer treatment, or palliative care.

This guideline is meant to help primary care clinicians deal with the 11 percent of adult patients that deal with daily pain.2 It was developed because primary care clinicians reported insufficient training in opioid prescribing and concern regarding addiction.

The guideline focuses on three main areas2

  1. Determining when to start/continue opioids for chronic pain and includes looking at treatment goals, discussing benefits/risks of therapy, and the utilization of not only opioid therapy but nonopioid therapy and nonpharmacological therapy.
  2. The selection, duration, dosage, follow-up, and discontinuation of opioids.
  3. Assessing the risk and addressing the harms of opioid use, which includes the use of methods to evaluate risks and reduce risk. It discusses the use of urine drug testing, the prescription drug monitoring program (PDMP), treatment of opioid use disorder, and precautions regarding co-prescriptions of benzodiazepines.

Recommendation 1

The first recommendation suggests that chronic pain should be managed primarily with nonpharmacologic therapies and nonopioid pharmacologic therapies. Opioid therapy should be considered only when consideration given to both the potential benefit in pain control and functional improvement versus the risks. When opiates are used, they should be combined with nonopioid and nonpharmacological therapy.

Appropriate non-pharmacological therapies include weight loss, physical therapy, exercise, psychological therapies, and selected intervention procedures (joint injections). Nonopioid pharmacotherapy may include NSAIDs, acetaminophen, cyclo-oxygenase (COX)-2 Inhibitors, some anticonvulsants, and some antidepressants. The use of nonopioid pharmacotherapy is associated with a significantly reduced risk of overdose.

Recommendation 2

The second recommendation suggests that before initiating opioid therapy in chronic pain patients, it is important to establish realistic goals for pain and function. Also, patient education given that opioid therapy would discontinue if risks of therapy deemed greater than the benefits. Opioid prescriptions should only continue when there is a meaningful improvement in function and pain, and the benefit outweighs the risk to patient safety.

Research suggests that long-term use of opioids is associated with serious risks, and that risk is dose-dependent. Research shows weak evidence that opioid therapy beyond six months results in clinically significant pain relief or clinically significant improvements in quality of life.35 Many patients who use long-term opiate therapy discontinue therapy due to adverse effects or inadequate pain control. Because of these facts, it is hard to predict which patient will have benefits greater than harm when receiving chronic opiate therapy.

When opioid therapy initiated, the prescriber should determine the assessment protocol of the effectiveness of therapy. Also, treatment goals should be established with the patient before starting therapy. Goals should include relief in both pain and improvement in function. Conditions that lead to progressive functional impairment or injuries such as spinal cord trauma may have a primary goal of pain relief as opposed to improvements in physical function. In addition, the consideration of the social and emotional well-being of patients should impact that assessment as well.

Functional goals may include returning to work, attending specific recreational activities, walking around the block, or taking the dog for a walk. Assessing for depression and anxiety as well as other psychological conditions is an important aspect of managing the whole patient. Generally, if pain and function are not improved on opioid therapy, tapering or discontinuing the opioid should be strongly considered.

A written agreement should also be used that discusses how opioids will be prescribed and monitored and how they will be tapered or discontinued. Situations, where opioids should be tapered or discontinued, including when opioids are not needed, side effects become too severe, or treatment goals not being met.2

Recommendation 3

The third recommendation suggests that providers should discuss the risks and benefits of opioid therapy both before and during treatment. Also, the responsibilities of both patient and clinician merit mandatory discussion before and during therapy.

Key teaching points:

  • Functionally improvement is the main goal, even if pain still is present.
  • The use of opioids generally does not improve pain and function in the long-term, but opioids may reduce pain in the short-term.
  • Discuss common side effects include nausea, vomiting, mental status changes, constipation, dry mouth, drowsiness, tolerance, physical and psychologic dependence, and withdrawal symptoms upon ceasing opioids.
  • Discuss potentially fatal respiratory depression, especially with higher doses or when used with other depressants such as benzodiazepines.
  • Chronic opioid use may lead to a lifelong opioid use disorder.
  • Increase fluid intake and fiber to reduce the risk of constipation.
  • Opioids reduce the ability to operate motor vehicles safely.
  • Discuss that the need for periodic review with consideration given to reducing or discontinuing the opioid.
  • Discuss the importance of not sharing prescriptions among family or friends.
  • Discuss safe storage, such as in a locked location.
  • Discuss safe disposal of controlled substances.
  • Discuss monitoring that will include the use of urine drug testing and the use of the prescription drug monitoring program.
  • Consider discussing the use of naloxone.

Recommendation 4

Recommendation number 4 suggests that when starting opiates for chronic pain, immediate-release opioids are recommended over longer-acting medications. Longer-acting opioids are associated with a higher risk of overdose when compared to immediate acting opioids.

The Food and Drug Administration (FDA) reported in 2014 that extended-release or long-acting opioid pain medications should be used when pain is severe enough to necessitate daily, around the clock long-term opiate treatment when other options are not effective, not tolerated or would not offer adequate pain management. They should not have use on an as needed basis.

Other key points under this recommendation include:

  • Certain medications are only appropriate for opioid-tolerant patients. An opioid-tolerant patient is defined as someone who has taken 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids for at minimum one week.36
  • There is not enough evidence to determine if taking immediate-release opioids for breakthrough pain when using ER/LA opioids is safe outside of palliative care, end of life care, and active cancer.2
  • The use of abuse-deterrent technologies makes it more difficult and less rewarding to manipulate the opioids. While they still can be abused, it is more difficult to do so. The abuse-deterrent technology does not prevent unintentional overdose, and the document from the Center for Disease Control does not make recommendations regarding abuse-deterrent formulations.
  • Research suggests Methadone having the highest number of overdose deaths when compared to other opioids when prescribed for chronic pain. Methadone also has cardiac complications such as QT prolongation and cardiac arrhythmias. In addition, methadone has a variable and long half-life, which can complicate when peak respiratory depression occurs. There is more interindividual variability in the pharmacodynamics of methadone when compared to other opioids. Methadone should only be used by prescribers that are very familiar with the unique pharmacodynamics and are willing to monitor patients on it closely.
  • The pharmacodynamics of transdermal fentanyl is also complex. A gradual increase in serum concentration can occur over the first 72 hours. Absorption can be variable based on factors such as external heat.
  • Initiation of Opioid treatment should not occur with ER/LA dosing, and this type of medication should not be used for intermittent use. They should be considered only in those who have severe pain and have used intermediate release opioids daily for at least seven days.

Recommendation 5

Recommendation five suggests that when starting opiates, the lowest effective dosage should take precedence. Extreme caution should be used when prescribing opiates. The risks versus benefits should be reevaluated with dosages above 50 morphine milligram equivalents (MME)/day used. If dosages above 90 MME/day used careful documentation of its justification should be accomplished.

Benefits of high dose opioids are not well established, and higher doses are associated with more harm such as opioid use disorder, overdose, and motor vehicle accidents.

While lower doses of opiates reduce the risk, there is no dose threshold eliminating the risk of overdose. Dosage above 90 MME/day is linked to a high risk of overdose with lower dosages associated with less risk. According to the CDC document2, when dosages pushed to over 50 MME/day, the risk of overdose increases without improving pain control or functional benefit.

When increasing the dosages of opioids, the increase should occur in the smallest amount possible to reduce the risk of overdose. There is no firm evidence on how long to wait before increasing dosages, but waiting at least five half-lives before increasing the dosage has been recommended.2 In addition, extreme caution should be used in individuals over the age of 65 or those with kidney or liver insufficiency.

When dosages are increased above 50 MME/day, the prescriber should:

  • Assess if the opiate is helping to meet the treatment goals
  • Increase the frequency of follow-ups
  • Consider providing naloxone
  • Provide overdose education

Even patients who have been on high doses for many years, the offer to wean their dosage should occur. The patient should have education regarding recent clinical evidence suggesting that patients on high doses of opiates are at higher risk for overdose, and the provider should offer the patient an opportunity to wean dosage slowly if indicated.

Recommendation 6

Recommendation 6 suggests that when using an opioid for acute pain, the provider should use the lowest dose of immediate-release opioids and provide a quantity that is no more than the expected duration that the patient needs. Three days or less is often enough, and more than seven days rarely indicated.

Some research suggests that for back pain managed in a primary care setting, the use of opioid medications results in a large reduction in pain until the fourth day of treatment, and after that, smaller pain reductions are noted. Opioids should not be prescribed “just in case.”2

Recommendation 7

Recommendation number 7 suggests that patients using opioids for chronic pain should have the benefits and harms evaluated within one to four weeks of beginning therapy or when there is a dose increase. After that, the benefits and harms should be evaluated at least every three months. If benefits do not outweigh the harms, the provider should consider tapering opioids to a lower dosage or discontinuing opioids.

Individuals who continue opioid therapy for three months or more are at increased risk of developing opioid use disorder.2 Therefore, frequent follow-up in the first three months may help reduce the risk of opioid use disorder. Another argument for close follow-up is that the risk of overdose is high during the first two weeks of treatment with ER/LA opioid use. The risk is especially high with methadone or fentanyl.

Research suggests that individuals who do not have pain relief from opioids at one month will likely not have pain relief at six months. Therefore, assessment within the first month is important to determine who will likely benefit from opioid therapy. Frequent assessments should reduce the risk of complications of long-term opioid use such as overdose, opioid use disorder, and other injuries.

Certain individuals are at higher risk for opioid use disorder or overdose, and this includes individuals with a history of a substance use disorder, individuals with depression or another mental health condition, patients taking greater than 50 MME/day, those with a history of overdose, and those taking other central nervous system depressant medications. These individuals should be evaluated more frequently. If found to be without benefit from the opiate, strong consideration should occur in reducing the dose or discontinuing the opiate.

When tapering opioids, the dose should be reduced weekly by 10-50%. In individuals who had a severe adverse event, such as an overdose, rapid discontinuation of 2-3 weeks could be utilized.2 For individuals who have utilized opioids for extended periods reducing dosages slowly may be appropriate. Reducing as slowly as 10% a month may be utilized in individuals who have been taking opioids for years.

A slow reduction in opioid doses reduces the signs of opioid withdrawal such as anxiety, nausea, vomiting, diarrhea, tremor, increased heart rate, insomnia, drug craving, and abdominal pain.

Recommendation 8

Recommendation number 8 suggests that risk factors for opioid-related harms should be assessed before starting therapy and during opioid therapy. In addition, clinicians should implement strategies to reduce risk in individuals at high risk. The strategies would include individuals on greater than 50 MME per day, those with a history of an overdose, a history of a substance use disorder, or those on concurrent benzodiazepines.

One strategy to reduce the risk of overdose death includes prescribing naloxone. Naloxone can reverse the opioid when there is severe respiratory depression. Naloxone has the potential to bring on acute withdrawal symptoms in patients who are physically dependent on opioids.

Other factors that place patients at high risk for overdose including those with sleep-related breathing disorders such as sleep apnea or congestive heart failure, pregnancy, mental health issues, those with renal or liver insufficiency, and those greater than age 65.

Pregnancy puts both mother and fetus at risk because it can increase the risk of poor fetal growth, congenital disabilities, stillbirth, and preterm delivery. It can also lead to neonatal opioid withdrawal. When prescribing opioids for anyone of childbearing age, it is important to discuss a possible consequence of opioids during pregnancy.

Prescribing medication, including opioids, can be challenging in older adults. Some of the concerns include reduced renal or hepatic function, higher risk of respiratory depression, increased risk of side effects including cognitive impairment, more comorbid medical problems, polypharmacy, higher risk of falls, and constipation.

Extra caution should be utilized in individuals with mental health problems when prescribing opioids. This group of individuals is at higher risk for opioid use disorder and increased risk for drug overdose (especially in those with depression).2 For individuals with significant psychiatric instability or high suicide risk, opioid therapy should not be initiated. Also, individuals who have been prescribed benzodiazepines should very cautiously be prescribed opiates, if at all.

The Patient should be asked about drug and alcohol use. In addition, the prescriber should use the prescription drug monitoring program (PDMP) database before prescribing. For individuals with a substance use disorder obtaining outside consultation with a substance use disorder specialist or pain specialist regarding the management of pain is recommended.

Recommendation 9

Recommendation number 9 suggests that the clinician should review the PDMP database to determine previous/current opioid prescriptions as well as other medications that may interact and place the patient at higher risk for overdose. The clinician should review this data at a minimum of every three months, but as often as every prescription written.

Research is limited on the benefits of PDMPs, but evidence suggests that individuals who received opioid prescriptions from multiple prescribers and at high doses are at the highest risk for overdose. The PDMP can help detect these situations.

Providers should not dismiss patients from their practice based on data received from these databases. Doing so has the potential to have negative health outcomes. The PDMP provides the provider and opportunity to intervene to reduce the risk of overdose by providing interventions as providing education, considering alternative therapies, or prescribing naloxone.

Recommendation 10

Recommendation number 10 suggests that when prescribing opioids for chronic pain, the use of urine drug testing should be used before the start of therapy, and at least once a year. The use of urine drug testing will ensure the patient is taking the medications as prescribed and that there are no illicit drugs in the patient’s system.

The use of other controlled substances increases the risk of overdose. Urine drug testing has the potential to identify these patients and reduce risk. Urine drug testing also can determine when patients are not utilizing prescriptions as prescribed, which may point to diversion or side effects that limit compliance.

While urine drug testing should be done before starting opioid therapy, there is disagreement with how frequently testing should be done during long-term therapy. It should be done at least once a year. In high-risk individuals, more frequent testing should ensue.

Patients should have educated regarding the purpose of drug testing; to improve patient safety. Before testing, the provider should ask about the use of other drugs or other medications, and if there might be any unexpected results. The clinician should be prepared for any unanticipated results and should have a plan for dealing with them. Unexpected results should be discussed with the patient to determine if there is a logical explanation. If the unexpected results (for example, negative for a prescribed drug or positive for an unexpected drug) are not explained, then confirmatory testing should occur.

Confirmed unexpected results can lead to one of the following outcomes.

  • Modification of the pain management strategy
  • More frequent evaluations
  • Tapering/stopping the opioids. When testing for expected medications is repeatedly negative, then abrupt discontinuation is appropriate (as the patient is not taking the medication)
  • More frequent re-evaluation
  • Giving naloxone
  • Referral for substance use disorder treatment
  • Clinicians should not remove the patient from care due to an unexpected urine drug test. The abrupt removal from treatment is a safety measure as the patient could have withdrawal or obtain medication from another source or even start heroin. It could also be construed as patient abandonment. Lastly, it may miss a chance to get the patient into treatment for substance abuse disorder.

Recommendation 11

Recommendation 11 suggests avoiding prescribing an opioid and benzodiazepine together. This combination reduces respiratory drive and significantly increases the risk of overdose. The recommendation is not an ultimatum to never prescribe these two agents together but should be done rarely and with extreme consideration. For example, a patient who has been on a long-term, low dose benzodiazepine and develops severe acute pain may be a candidate for a low dose opiate medication.

Other medications that suppress the central nervous system should be avoided in those on opiates. These may include sedatives, hypnotics, muscle relaxants, some antidepressants, and sedating antihistamines.

Recommendation 12

Recommendation number 12 recommends using an evidence-based treatment in those with opioid use disorder, which may include medication-assisted treatment (MAT) with behavioral therapy.

Points discussed under this recommendation include:

  • Opioid dependence is estimated to be present in between 3-26 percent of primary care patients on opioids for chronic pain. The use of MAT is effective in preventing relapse in those with opioid use disorder.2
  • MAT can occur with buprenorphine or methadone and, in some cases, naltrexone. Naltrexone blocks opioids effects and can be given as daily oral therapy or as monthly injections.
  • Providers should be aware of community resources available to help patients get treatment for opioid use disorder.
  • The use of MAT in pregnant women with opioid use disorder improves maternal outcomes. Treatment should be with buprenorphine or methadone, not naltrexone.

The CDC guideline aims to enhance the communication between patient and provider regarding the risks and benefits of opioid treatment in chronic pain. It also looks to reduce the risks of long-term opioid therapy and improve effectiveness and safety.

Risk Factors for Opiate Abuse

The health care industry should shoulder some of the burdens of the opioid epidemic. The 1990s were a time when pharmaceutical companies aggressively marketed pain medications. Healthcare providers, encouraged by the Joint Commission, were encouraged to assess pain and manage it appropriately. The combination of intense assessment and pharmaceutical companies marketing pain medication was partially responsible for the increased use of opioid pain medications. Also, support was given to multiple medical organizations, including the American Pain Society, the Federation of State Medical Boards, and the American Academy of Pain Medicine that lobbied for aggressive identification and management of pain.38

Research from 2015 showed that six times more opioids were dispensed in counties with high prescribing rates versus counties with low prescribing rates. Certain characteristics make prescribing controlled substances more likely. The CDC reported risk factors for counties at higher risk for prescribing more controlled substance including a higher percentage of white people, more patients with diabetes, arthritis, or disability, when a higher percentage of people were unemployed or uninsured, counties with more dentists or primary care physicians, and counties with small cities or large towns.39

There are many known risk factors for opioid abuse, misuse, diversion, addiction, and overdoses.40 Evaluating these risk factors remain an important aspect of the evaluation of a patient. Factors that increase the risk of problematic opioid use include:

  • A prior history of misuse or abuse
  • Younger age
  • Untreated psychiatric disorder
  • Living in a social and/or family environment that encourages misuse
  • Genetics
  • Physical, sexual or emotional abuse
  • Using nicotine, alcohol or other drugs at an early age
  • Substance use/abuse in the family or among friends
  • Stress
  • Access to addictive substances
  • Highly impulsive personality
  • Family or personal history of drug/alcohol abuse and mental health issues including depression, anxiety, eating disorders, or personality disorders
  • History of legal trouble/incarceration
  • White race

Prescription drug misuse is the use of prescription medication in a method or intent inconsistent with its prescription. This includes using medication to get high, selling or sharing it with other (diversion), overuse, having multiple prescribers, and concurrent use of alcohol or other illicit substances. Misuse is necessary but not solely enough of a criterion for a substance use disorder.

Susceptible individuals are at risk in the misuse of medications that stimulate the reward center of the brain, which may include opioid analgesics, stimulants, benzodiazepines, or tranquilizers.

Prevention of Misuse

To prevent prescription drug abuse, the clinician needs to assure:

  • Patients are assessed and reassessed
  • Treatment agreements in use
  • Prescription monitoring occurs
  • The practice of safe prescription methods

Patients' risk should be assessed, with contraindications immediately identified. Contraindications to opioid treatment include those who have erratic follow up, suffer from current untreated addiction, or have poorly controlled mental illness.41

Assessment

When taking a patient history document, the opioid currently prescribed, its dose, the frequency of use, and the duration of use. It is important to query the state prescription drug monitoring program to confirm the patient’s report of prescription use. In addition, it is important to contact past providers to obtain medical records.

A history of illegal substances use, alcohol use, tobacco use, prescription drugs use, psychiatric history, family history of substance abuse and psychiatric disorders, history of sexual abuse, legal history, behavioral problems, employment history, marital history, social network, and cultural background should be assessed in all patients who are being considered for controlled substances. History of substance abuse does not prohibit treatment with opioids but may necessitate more intensive monitoring or referral to an addiction specialist.

Multiple tools are available to evaluate opioid risk. The Opioid Risk Tool is a tool that is used in primary care to screen adults for the risk of aberrant behaviors when prescribed opioids for chronic pain. It is a copyrighted tool, encompasses five questions, and takes about one minute to use. It classifies a patient as low, moderate, or high risk to abuse opioids. Those who are high risk have a high likelihood of aberrant drug-related behavior. The five questions include asking about family and personal history of substance abuse (alcohol, prescription drugs or illegal drugs), age (risk is 16-45 years old), psychological disease, and history of preadolescence sexual abuse. The questions are scored with different points assigned for each question, which is variable between men and women, and a total score is tallied. The patient is placed in low, moderate, or high risk.

Follow Up

Regular follow up is important and should occur at a minimum of every three months. When assessing the pain patient, include the five A’s, which are: analgesia, addiction, activities of daily living, adherence, and adverse effects. Part of follow up should be urine drug testing to detect medication adherence as well as illicit and non-prescription drug use. It is critical the clinician adequately document any and all interactions with patients, assessments, results of testing, and treatment plans.

Written treatment agreements, which should be used between prescribers and patients when controlled substances prescribed. The agreement helps guide the conversation between the patient and the prescriber. It discusses expectations, the risks, and the monitoring that will occur to limit the complications of controlled substances (Table 2).

Table 2: Points Commonly Seen in Opioid Agreements
  • Early refills will generally not be given
  • Patient will not seek controlled substances from another provider
  • Patient will use only one pharmacy
  • Permission for the prescriber to speak freely with other health care providers, pharmacists and family members regarding opioid use
  • Patient will submit to urine drug test
  • The patient will safeguard the medications
  • Discuss the common side effects of the medication

Clinician Response

How should the clinician respond when abuse or misuse detected? If it is a singular, minor deviation, then counseling, along with more intensive monitoring may suffice. Tapering controlled substances to reduce the risk of withdrawal is appropriate in more severe or persistent cases of misuse. When diversion is the cause of misuse, immediate removal of the prescription is likely the best course. If a substance abuse disorder is suspected, recommend a referral to an addiction specialist.

Safe prescription methods are listed below in the section on prescribing controlled substances.

Prescribing Controlled Substances

Steps a prescriber can take include31:

  1. Assessment and documentation of a comprehensive history including medical history, substance abuse history, current medications including dosages, route and time, psychiatric and psychosocial history.
  2. Establishing a physical and psychological diagnosis and establish medical necessity before starting or maintaining controlled substances. Those with mental illness are at higher risk for medication abuse.
  3. Screening for substance abuse history because substance abusers are at increased risk to misuse controlled substances.
  4. Establish goals in therapy regarding pain control and functional goals.
  5. Using prescription monitoring programs to help determine patterns of prescription use and reducing abuse of medications. These are state-run databases that track controlled substance prescriptions and help find issues with overprescribing and misuse patterns.
  6. Use urine drug testing to identify noncompliance or aberrant drug use.
  7. Consider contraindications before prescribing opioids such as acute psychiatric instability, uncontrolled suicide risk, opioid allergy, respiratory instability, history or current abuse of substances or alcohol, current use of benzodiazepines, current use of heavy doses of other central nervous system depressants, current use of other medications that have severe drug interactions or those who practice diversion of controlled substances.
  8. Judicious utilization of imaging tests and other evaluations as some testing may increase fear, foster activity restriction, encourage maladaptive behaviors and encourage requests for more opioids.
  9. A written agreement between the prescriber and patient when controlled substances are used that reduce the risk of abuse, diversion, misuse, and overuse.
  10. Discuss the risks and benefits of the medications.
  11. Obtain informed consent before prescribing controlled substances.
  12. In general, start opioid therapy at low doses with short-acting medications.
  13. Use long-acting opioids in high doses only for severe, intractable pain that cannot be adequately managed with short-acting opioids or moderate doses of long-acting opioids.
  14. Use caution when titrating with long-acting opioids and considering the potential for overdose and misuse.
  15. Consider consultation for those who require high-dose opioid therapy.
  16. Ensuring only one prescriber of all opioids for a given patient.
  17. Monitoring for and managing constipation.
  18. Prescribing the lowest effective dose and the smallest quantity needed based on the expected length of the symptoms.
  19. Review the treatment plan regularly to include any new information about the patient, their condition, and their pain and progress toward their goals.
  20. Keep accurate records.
  21. Ensure compliance with all laws and regulations related to controlled substances.
  22. Individualize treatment based on the patient’s prior exposure to the controlled substance, response to treatment, and adverse events.
  23. Monitoring for aberrant drug-related behaviors.
  24. Discontinuing chronic controlled substance therapy in those who repeatedly engage in aberrant drug-related behaviors, do not progress toward established goals or those who experience significant side effects. Patients who have been taking the opioid for an extended time should have the medication tapered slowly. A 10% taper per week will minimize the symptoms of withdrawal. Some recommend a faster taper such as 20 – 50% per week for those who are not addicted.42

Tips to Reduce Iatrogenic Harm

  • Have an upper dosing threshold. The risk of accidental overdose increases with higher doses of opioids. Risk increases at 50 MME/day. Prescribers should generally avoid doses of morphine or morphine equivalents more than 90 - 200 MME/day.43
  • Use caution with certain medications. For example, methadone should only be used by a prescriber who is extremely comfortable with the medication. Fentanyl is another medication that requires extreme caution as there is unpredictable absorption – especially with the patch.
  • With opioid use, respiratory depression is more likely in the older population and those who are cachectic or debilitated. Monitor patients at high risk more closely, and do give opioids in combination with other respiratory depressants. The dose of opioids should be started at one-third to one-half of the typical starting dose in at-risk patients. Titration opioids carefully. Constipation is more likely, and a bowel regime should be prescribed when opioids in use.
  • The greatest risk of opioid use is respiratory arrest and death, and this risk is greatest when therapy started or the dose increased. Opioid-induced respiratory depression manifests by the reduced desire to breathe and reduced respiratory rates. The patient will be breathing shallow, and CO2 retention can exacerbate the sedating effects of opioids. If respiratory depression noted, the family should call 911.
  • Opioids should not be used in those with respiratory depression. Titration must occur slowly, and when changing formulations, do not overestimate the converting dosage.
  • Avoid combinations of opioids and benzodiazepines. When these two classes are combined, particularly if more than 100 mg of morphine or morphine equivalents per day is used, the risk of accidental overdose is high.
  • Pay attention to drug-to-drug and drug-to-disease interactions.

Recommendations on Limitations of the Length of Prescriptions

Opioid overdose is a continuing public health crisis, and states have taken steps attempting to reduce the overuse of these medications in hopes of reducing overdose and other negative outcomes. Organizations, including the CDC, have made recommendations regarding the amount or duration that opioids should be prescribed.

The goal of pain management should be tolerable pain levels with good function. Here are some guidelines for how long medications are prescribed to those with acute pain.19

  • Mild pain syndrome should generally be treated with acetaminophen and/or nonsteroidal anti-inflammatories along with nonpharmacological therapy.
  • Individuals who suffer from moderate pain, such as after minimally invasive surgery, simple fractures, and soft tissue surgery, a 3 to 5-day course of oxycodone may be appropriate.
  • For individuals who suffer from severe pain such as those from a major surgical procedure, total joint replacement, compound fracture, higher doses of opioids may be used for up to one week.
  • One study looked at the number of pills prescribed after procedures for 80% of patients and showed that those after laparoscopic cholecystectomy, laparoscopic inguinal hernia repair, or an open inguinal hernia repair required 15 pills of oxycodone 5 mg. In contrast, partial mastectomy patients required five pills.44
  • Predicting the number of medications patients will need after discharge from their procedure can be ascertained from the number of pills the patient took the day before discharge. One study showed that patients who took 1 to 3 pills on the day before discharge from the hospital took a mean of 7.6 pills after discharge from the hospital. Individuals who took four pills on the day before discharge took a mean of 21.2 pills after being released from the hospital.45

The Iowa Department of Public Health evaluates the number of prescribers enrolled in the Board of pharmacy’s prescription drug monitoring program. Factors that are evaluated by the Iowa Department of Public Health include the average MMEs prescribed per day, the total number of days for the prescription written, and the total number of opioid prescriptions written. Recent data suggests that over the last few years, the strength of the dosing is not decreasing, and the number of days of prescribing is increasing.46

The state of Iowa has implemented administrative codes regarding opiate use. According to Iowa Administrative Code (IAC) 657-10.29(124), “[a]n individual prescriber may issue multiple prescriptions authorizing the patient to receive a total of up to a [ninety]-day supply of a Schedule II controlled substance according to the provisions and limitations of this rule.”, Refills are prohibited. IAC 657-10.25(3) states, “Each separate prescription, other than the first prescription if that prescription is intended to be filled immediately, shall contain written instructions indicating the earliest date on which a pharmacist may fill each prescription.”47

According to IAC 657-10.29(6), “Nothing in this rule shall be construed as requiring or encouraging an individual prescriber to issue multiple prescriptions according to this rule or to see the prescriber’s patients once every 90 days when prescribing Schedule II controlled substances. An individual prescriber shall determine, based on sound medical judgment and in accordance with established medical standards, how often to see patients, and whether it is appropriate to issue multiple prescriptions under this rule.”47

According to IAC 657—10.32(124), “No prescription for a controlled substance listed in Schedule III, IV, or V shall be filled or refilled more than six months after the date on which it was issued nor be refilled more than five times. Beginning January 1, 2020, all prescriptions for controlled substances shall be transmitted electronically to a pharmacy according to rule 657—21.6(124,155A), except as provided in rule 657—21.8(124,155A). 10.32(1).”47

The board may discipline an ARNP for prescribing opioids in dosage amounts that exceed what would be prescribed by a reasonably prudent ARNP in a similar practice.49

Patient Education on Opioid Medications

Patient education is important as it will reduce the risks associated with these medications and result in improved pain management. Patients need education in the safe use, storage, and disposal of opioid medications. Safe use of opioids requires the patient to know about adverse events, as well as risks of abuse, misuse, and addiction.

An overdose occurs when someone takes a higher dose than the body can tolerate leading to a significant adverse effect. Respiratory depression is the primary risk. This risk is highest in those who are not tolerant to opioids, take other respiratory depressants, have multiple health conditions, or have debilitated health and/or an impaired respiratory function.

Medications associated with a high risk of respiratory depression are schedule II opioids. Fentanyl, a synthetic opioid pain reliever, is 50 to 100 times more potent than morphine and has been implicated in many cases of overdose death. Medications that are altered for administration also increase the risk of overdose. Snorting, injecting, inhaling, chewing, or dissolving medications that should be swallowed whole (particularly extended-release opioids) increases the risk. Other methods that may lead to overdose include rapid titration of opioids and overestimation of the dose when converting from one opioid to another. Medication overdoses also occur when taken by someone it was not prescribed for, especially children. Therefore, safe storage and disposal are critical.

Patient education should include information on abuse. Many patients, who end up abusing opioid medications, usually got a valid initial prescription. Most patients who abuse medications get them either by buying or stealing from an acquaintance (most typically a friend or relative).50

Patient education should also include information on misuse. Many patients will misuse medications because they are seeking to improve function, have uncontrolled pain, or are using them to manage stress or mental disease. Aberrant behavior may manifest in those who are undertreated for pain. In the absence of addiction, these behaviors cease when pain is adequately controlled.

The patient's teaching must include zero tolerance for drug diversion and that it will result in immediate termination of the prescription with referral to a substance abuse program and possible legal action.

Patients should be taught about addiction. Addiction is a chronic disease with psychological, social, genetic, and environmental factors influencing its presentation and development. Addiction presents with the drug craving, compulsive use, impaired control, and persistent use despite harm.

Drug Take-Back Programs provide a convenient way for patients to dispose of unneeded, expired, or unused controlled substances. If no program is available, the patient must use extreme caution when disposing of controlled substances. Improper disposal may lead to environmental complications or drug diversion. Controlled substances can be mixed with cat litter or coffee grounds then sealed in a non-leaking container.

Key points in patient education include:

  • Goals of treatment.
  • Alternative treatment options.
  • Patients should be encouraged to read their medication guide and/or the package insert every time they get a new prescription.
  • Teach about abuse, addiction, misuse, and diversion.
  • Risks of overdose and/or death if dose not taken exactly as prescribed or someone else takes the medication.
  • Pain medications may impair breathing.
  • Do not give the medication to anyone else.
  • If anyone else takes the medication, to contact emergency services.
  • Swallow pills whole that are meant to be swallowed – do not crush, snort, chew, inhale, or take by any other means other than the method prescribed.
  • Maintain contact with the prescriber for monitoring and titration.
  • Teach about drug-to-drug interactions. Medications that should be avoided in combination with opioids include alcohol or any medication that the patient does not have a prescription. Medications that should only be taken after a careful review and counseling by a prescriber include sedatives, hypnotics, anxiolytics, antidepressants, and antihistamines.
  • Opioids may lead to cognitive impairment and may affect driving ability or safety at work, especially if operating heavy equipment.
  • Opioids should be stored safely and away from family members, acquaintances, and friends.
  • Medications should be locked up in a drawer, cabinet, or safe so no one else will get them.
  • Educate patients that it is illegal and dangerous to give away or sell their medications to others.
  • Patients should keep track of the number of pills, capsules, etc. - so it can be determined if any are missing.
  • Do not store them in a pill reminder container.
  • Teach about common side effects: sedation, drowsiness, respiratory problems, dizziness, mental status changes, nausea, vomiting, constipation, anxiety, tremors, and diaphoresis.
  • Monitoring will take place in the form of pill counts, urine drug screens, and the use of the prescription drug monitoring program. Unfavorable results may lead to termination of treatment or alteration in the treatment plan.

Termination Strategies for Chronic Therapy

Discontinuation of opioid therapy may be considered if problematic patterns are noticed, opioid therapy is not effective, or goals are not being achieved. The prescriber and patient must agree upon reasons to terminate therapy before initially prescribing the medications and should be part of the initial agreement.

The clinician should have a method for addressing prescription drug misuse. Minor infractions may result in patient counseling and intensifying monitoring activities. More severe behaviors may require the clinician to discontinue prescribing controlled substances. If patients are found to be diverting prescription medication, immediate cessation of the prescriptions is appropriate. In most other cases, it is appropriate to taper the controlled substances to reduce the risk of inducing a withdrawal syndrome.

When stopping the medication, the patient and the prescriber must agree to stop the medication. For patients who decide to continue treatment with another prescriber, the prescriber may consider maintaining the current dose for four weeks.

When appropriate, implement a tapering schedule to avoid withdrawal. A reduction of 10% every 7 to 14 days until the patient gets to a lower dose, at which time a 5% reduction every 2-4 weeks may be done.

Offer Individuals who have shown aberrant behavior other non-opioid options. For patients who have engaged in criminal activity (such as diverting drugs or altering prescriptions), should be referred to a substance abuse treatment program and may be discharged from the practice.

Case Study 1

Jack C is a 38-year-old male with chronic back pain due to three herniated discs and spinal stenosis, which was first diagnosed after a motor vehicle accident three years ago. He currently rates the severity of his back pain as a 9/10 and has been unable to work as a plumber due to his pain. He describes the pain as dull and constant with occasional sharp exacerbation in the low back with the pain increasing with bending, prolonged standing, and walking. The patient denies any loss or change of bowel/bladder control, history of IV drug use, recent infection, progressive neurological complaints, night pain, night sweats, weight loss, or fever. The pain radiates into the right leg to the knee, and he describes this pain as burning and tingling. The patient can do all his activities of daily living but does report poor sleep at night.

He has a past medical history of hyperlipidemia. His only current medication is atorvastatin to control his cholesterol.

He has had multiple treatment modalities, including four rounds of physical therapy, chiropractic treatment, and multiple medications. He tried to control his back pain on acetaminophen, ibuprofen, and topical non-steroidal anti-inflammatory agents without relief. The patient experienced significant tremors and an increase in blood pressure while on tramadol. A series of epidural injections did not help. The patient refused surgery as an option when discussed.

Jack is married and has one daughter who lives over 500 miles away with her biological mother. He has limited financial means and lives paycheck to paycheck. He has a prior history of alcohol abuse but has not had a drink in five years. He is currently a smoker. He denies any history of substance abuse, and there is no family history of alcohol or substance abuse.

Physical exam showed a patient with a slow, deliberate gait, a limited range of motion in the spine with no obvious deformity, swelling, or erythema. There is mild tenderness on the right side of the spine from the area of L4 to S1 as well as tenderness in the right sacroiliac joint. Normal reflexes, normal sensation, normal strength, and no atrophy noted in the lower extremities. The straight leg raise test is normal.

An MRI performed one year ago showed a herniated disc at the L5/S1 level and mild spinal stenosis.

The Opioid Risk Tool was administered and determined the patient is at moderate risk for opioid abuse. He signs a written opioid treatment agreement that outlines the conditions of opioid therapy. His past medical records were verified, suggesting he is not lying.

After the state’s PDMP was accessed, it was determined that he had not gotten any controlled substances for the last two years. The patient is prescribed hydrocodone/acetaminophen 5 mg/500 mg, two tablets every six hours as needed (56 tablets) for one week.

He returned to his primary provider, who was uncomfortable prescribing him long-term opiates, so he was referred to a pain specialist. The pain specialist continued the hydrocodone/acetaminophen two tablets every six hours as needed for pain. At the same time, he was started on gabapentin 100 mg three times a day, and then after one week, the dose was increased to 300 mg three times a day to manage the neuropathic pain. He is also started on a lidocaine patch. The patient was told to follow up in two weeks to assess effectiveness. After two weeks, the patient reports he is more functional, and the pain is improved. The dose of the gabapentin was increased to 600 mg three times a day. After two more weeks, he reports he is feeling better and wants to stop the hydrocodone/acetaminophen. He continues the gabapentin and lidocaine patch and uses a combination of acetaminophen and naproxen for breakthrough pain.

Case Study 2

Ms. L is a 46-year-old female with a history of bilateral knee pain; she currently rates the pain as an 8/10 in her right knee and 5/10 in her left knee. She takes MS Contin 60 mg every 12 hours with immediate-release tablet of morphine dosed 15 mg every 8 hours as needed (she averages one dose a day) and been using this regime for the past six months, but over the last month, she has not been getting adequate relief from her pain and has been progressively disabled and has stopped exercising.

The pain is attributed to osteoarthritis and has been progressively worsening over the last 1-2 years. She has a past medical history of anxiety and depression but does not take any medication for these conditions. She has a past-surgical history of a hysterectomy approximately three years ago and takes no other medications. She has no known allergies.

She has no history of alcohol, drug, or substance abuse. She has a strong family network, including a supportive husband of 25 years and two sons who live within twenty miles of her home.

The physical exam is significant for obesity (BMI of 34). She has crepitus to both of her knees and is unable to reach full extension of the right knee due to pain.

An x-ray demonstrates moderate arthritic changes in both knees. The patient is unwilling to consider surgery of her knees.

After the state’s PMPD was accessed, it was determined that he had not gotten any controlled substances other than the morphine for the last two years. A urine drug screen was positive for morphine, but no other substances.

The prescriber offers meloxicam and a knee injection in her right knee. She is agreeable to a follow up in two weeks, which at that point, there is a noted improvement in her pain level as well as the amount of enjoyment she gets out of life. She reports she has not used any breakthrough morphine dosing. The nurse practitioner increases the dose of meloxicam and gives her an injection in her left knee and has a conversation about weaning the morphine dosing. The patient is agreeable to weaning dose of morphine by 10 mg every 1-2 weeks with frequent follow-up to assess pain control. Over the next year, she can wean off morphine while continuing the meloxicam. In addition to the meloxicam, she was able to lose 20 pounds, which she attributes to her improved quality of life and improved ability to function.

Conclusion

Pain is a disagreeable sensory and emotional experience connected with actual or potential tissue damage or explained in terms of such damage. Many conditions have the potential to cause pain. Understanding these conditions, how to assess them, and how to treat them are a vital part of adequately managing the pain.

It is the role of the provider to perform a good initial pain assessment and an on-going assessment of pain. Many options are available for the management of pain, including non-pharmacological options, non-opioid medications, opioid medications, and adjunctive medications. Opioid analgesics, while very good at managing pain, have led to many social and legal problems, including overuse and diversion.

The Center for Disease Control published guidelines in 2016 that help clinicians safely and effectively prescribe opiates. The guidelines incorporate 12 recommendations that mean to improve patient care and assure patients have prescribed opiates safely and effectively. This course discussed methods to assess for patients at risk for opiate abuse and provided tips for safe and effective prescribing.

Select one of the following methods to complete this course.

Take TestPass an exam testing your knowledge of the course material.
OR
Reflect on Practice ImpactDescribe how this course will impact your practice.   (No Test)

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