Broglio, Kathleen DNP, ANP-BC, ACHPN, CPE; Cole, B. Eliot MD, MPA
Over 100 million Americans suffer from chronic (persistent) pain, affecting their quality of life, with financial costs greater than $560 billion annually.1 In the late 1990s, healthcare providers began prescribing opioids for chronic noncancer pain (CNCP) after changes in the state medical board policies.2 The impetus to end the undertreatment of pain continued with The Joint Commission pain standards in 2001.3 In an effort to treat pain, the number of opioid prescriptions tripled between 1990 and 2009 to over 200 million annually.4 However, studies on efficacy and safety of long-term opioid use for CNCP were limited, as most studies never extended beyond 12 weeks.5,6
The increased use of opioids for pain was associated with the unintended consequence of abuse and resulting morbidity and mortality. The illicit use of prescription opioids by approximately 4.9 million persons ages 12 years and older is second only to marijuana use.7 Death secondary to nonmedical prescription drug use is now greater than deaths related to heroin and cocaine combined and, in some states, it is the number one cause of accidental death.7
Due to the increasing morbidity and mortality from prescription drug abuse, the Office of National Drug Control Policy implemented strategies to reduce prescription drug abuse, including: expansion of state-based prescription drug monitoring programs, medication disposal, education for providers and patients, reduction of “pill mills,” and “doctor shopping” through law enforcement.8 As part of the effort, in July 2012, the FDA approved the final Risk Evaluation Mitigation Strategies (REMS) for extended-release and long-acting opioids.9 Elements of the REMS for opioids include responsibility of pharmaceutical manufacturers to provide educational activities about extended-release and long-acting opioids; a patient counseling document regarding responsibilities and safety; and an updated patient medication guide about safe use and disposal.9 While these efforts may increase some providers' knowledge about opioids, the education is not mandatory and may not be accessed by all prescribers.
Primary care providers care for many people with CNCP and are the dominant prescribers of opioids.10,11 Providers may have inadequate knowledge and training, misconceptions about prescribing, and may require additional education and tools for managing pain.11–13 Results from recent studies highlight that providers may not utilize risk management strategies when evaluating and prescribing opioids for chronic pain.11,14,15
Nurse practitioners (NPs) may be uncomfortable prescribing opioids due to a lack of confidence in treating chronic pain and choosing the appropriate medications, fear of regulatory oversight, and concern about being seen as different from other prescribers. Other barriers to prescribing include concerns about medication costs and addiction risks.16
Why would NPs consider prescribing opioids for CNCP given the increasing abuse of opioids and the lack of adequate data about the long-term efficacy of opioids? The answer may be found in patients with moderate-to-severe CNCP secondary to conditions such as osteoarthritis, low back pain, or neuropathic pain, who are treated in the primary care setting. These individuals may have tried nonopioid therapies and nonpharmacologic strategies without adequate efficacy or may have comorbidities that limit the use of medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen.17 These individuals may be older, have limited options, and may benefit from opioid therapy.
NPs must take a balanced approach and recognize when opioids should be an appropriate part of the treatment plan. The same could be said if one were treating patients with pain secondary to cancer and advanced diseases. However, there are more considerations in the treatment of this population that are beyond the scope of this article. What follows are tips for opioid prescribing from a clinician's perspective. This information should be balanced with appropriate continuing education, which includes changes in policies related to opioid prescribing.
A comprehensive assessment is the first step in planning pain management strategies. The NP must determine the duration of the pain. Acute pain secondary to injury or surgery is expected to resolve once healing occurs. Chronic pain is usually defined as persisting for more than 3 months or past the period of expected healing. The NP must also determine if the pain is nociceptive or neuropathic, as treatment will be directed at the type of pain experienced.18 The pain assessment should include provoking and relieving factors as well as past pharmacologic and nonpharmacologic pain treatments. The NP should assess for effects of pain on quality of life, such as sleep, activity, emotions, and relationships with others.19
It is important to assess for depression and anxiety, which may be present in 50% of people with chronic pain and may affect the individual's coping ability.20 NPs should also assess if the patient is self-medicating to treat the pain. If necessary, a referral should be made to psychology or psychiatry. A pain assessment tool or a standardized template can ensure a comprehensive assessment. Establishing a diagnosis through a comprehensive history, physical exam, and diagnostic testing is an essential part of treatment planning.17,21,22 In the acute phase of severe lower back pain, for example, it may be appropriate to prescribe a limited amount of an opioid such as hydrocodone-acetaminophen without a complete diagnostic workup if non-opioids such as NSAIDs or acetaminophen are ineffective. However, if the pain persists for more than 3 months, the NP must establish a diagnosis and implement multimodal therapy before considering chronic opioid therapy.
Considerations for initiating opioids to treat CNCP
What is the best treatment for individuals who may have, for example, severe pain secondary to osteoarthritis and diabetic peripheral neuropathic pain? These individuals may have decreased function despite physical rehabilitation efforts. Recommended treatment strategies for osteoarthritis such as acetaminophen, NSAIDs, and topical agents are ineffective. These patients may have multiple comorbidities and may not be candidates for corticosteroid injections or joint replacement therapy. For neuropathic pain, guideline recommendations for first-line treatment include the use of tricyclic antidepressants (nortriptyline [FDA off-label use]), dual reuptake inhibitors of serotonin and norepinephrine (duloxetine, FDA approved for diabetic peripheral neuropathic pain and chronic musculoskeletal pain, but often used off-label for other neuropathic syndromes), or calcium channel alpha-2 delta ligands (gabapentin, FDA approved for post-herpetic neuralgia and pregabalin, FDA approved for diabetic peripheral neuropathic pain, postherpetic neuralgia, and neuropathic pain secondary to spinal cord injury [both often used off-label for other neuropathic pain syndromes]).23 Although the evidence for opioid efficacy for neuropathic pain is equivocal, opioid therapy to maintain or improve function may benefit this individual.17,24
Opioids may be considered if pain is moderate-to-severe and impacts the individual's quality of life with persistent pain. Opioids are only one aspect of multimodal treatment for CNCP, which could include multiple classes of medications, such as NSAIDS, adjuvant medications for neuropathic pain, and topical agents. Nonpharmacologic treatments such as exercise and rehabilitation therapy should be included in the treatment plan. In some cases, interventional therapies may be appropriate.25 However, opioids should only be initiated after a comprehensive evaluation, establishment of a diagnosis, and a risk evaluation for potential misuse or addiction.21 Initiation of opioid therapy is essentially a “trial” to assess for efficacy, which should be explained to the patient.21 All of these modalities in combination may improve the function and quality of life, and when applicable, may facilitate return to work but not necessarily ameliorate the pain. Conversations regarding realistic goals related to the pain should occur when designing treatment plans.
Understanding the basics regarding opioid therapy is imperative for all prescribers. Although primary care NPs may not have the time to develop in-depth knowledge of opioid therapy, basic principles of prescribing are necessary for safe and responsible prescribing. REMS programs will provide the basic information necessary to safely prescribe opioids.26
Opioid risk evaluation
Guideline recommendations have indicated that risk assessment should be an integral part of the decision to initiate opioids.21,22,27,28 Prior to starting opioids, validated risk evaluation tools (available online) such as the Diagnosis, Intractability, Risk, Efficacy Score, Opioid Risk Tool, and the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) can aid in the risk assessment.29–31 The SOAPP-R and psychological assessment are considered superior to other risk evaluation tools, but the decision of which tool to use should be based on the ability to implement it within the clinical practice.32 If the outcome of the risk evaluation shows the individual has a low-risk score, then opioids may be a consideration. However, if the history and risk score indicates that the individual is at increased risk due to history of substance use and concurrent psychiatric disorders, management in conjunction with a pain specialist is recommended. Pain management specialists should manage opioid therapy for those high-risk individuals who have active substance use disorder or major untreated psychopathology.33
For patients who are already on opioids, the Current Opioid Misuse Measure is a tool for monitoring adherence to therapy.34 The Pain Assessment and Documentation Tool (PADT) assesses for effects of analgesia, activities of daily living, adverse reactions, and aberrant behavior.35,36 Even if the NP does not use the PADT, documentation should reflect the response to analgesia, changes in activities of daily living, adverse reactions to opioids, and signs of aberrant behavior (also known as the four As: analgesia, activities of daily living, adverse reaction to opioids, and aberrant behavior). The results of the risk assessment and reassessment, and future plan for care, should be accurately reflected in the documentation.
Risk factor assessment for adverse reactions to opioid therapy should be part of the initial risk assessment and should be reassessed on a routine basis. Medication reconciliation should be conducted to assess for drug-drug interactions.6,17,21,22,28 It is pertinent to also assess for sleep and obstructive pulmonary disorders that can put the patient at increased risk for adverse events secondary to opioids.21,22 Although the American Geriatric Society has recommended opioids for older adults with moderate-to-severe pain, results of a study of Medicare recipients found more adverse events and all-cause mortality for older adults on opioid therapy.37,38 Therefore, NPs must carefully weigh the risks and benefits prior to initiating opioid therapy.
Once therapy has been initiated, it is important to assess for the adverse reactions or lack of efficacy to opioid therapy at each visit. Twenty-two percent of individuals discontinue oral opioid therapy, and 12.1% discontinue transdermal therapy due to adverse reactions, while 10.3% discontinue oral therapy and 5.8% discontinue transdermal therapy due to lack of pain relief.39 Constipation is the most common long-term adverse reaction and occurs in up to 70% of individuals40; it is often not reported and may lead to discontinuation of opioid therapy. Adverse reactions such as nausea, pruritus, sedation, and cognitive slowing usually resolve once an individual develops tolerance to the opioid, but the patient should also be assessed at each visit, as these continued adverse reactions may necessitate opioid dose reduction or rotation.41
Urine drug testing (UDT)
Reports on the efficacy and adherence to opioid therapy are subjective measures. UDT is the only objective measure to see if the patient is taking what is being prescribed and to evaluate for the presence of illicit drugs or prescription medications that have not been prescribed. Robust evidence for the use of UDT to prevent misuse does not exist, but UDT prior to initiating opioid therapy and during chronic opioid therapy is strongly recommended.21,22,27,28,42,43 There are two levels of UDT. Point-of-care testing such as “dipstick” enzyme immunoassay can be performed in the office setting. This test will evaluate for the presence of classes of medications, such as opioids, but not the specific opioid, and they usually will not detect synthetic opioids or illicit drugs, such as hallucinogens. Due to the low sensitivity and specificity, the test is not useful for those on chronic opioid therapy. The use of gas chromatography/mass spectrometry is considered the gold standard for UDT.43
The NP needs to understand the capabilities and limitations of the tests, the cutoff points, and how to read the results. Most companies will provide education and support about the interpretation of results. NPs must be cognizant of the costs and the patient's insurance coverage of the tests. No consensus exists regarding the frequency of urine drug testing, but it is best to perform the test on an unannounced basis. The decision may be made to test only once a year for those who are not considered to be at high risk.
When collecting a UDT, it is important for NPs to ask about and document the names and the timing of the last dose taken for all medications as well as the use of any illicit substances. UDT results can be surprising even for patients who may be considered at low risk, such as the case of a 75-year-old woman with multiple comorbidities with opioids present in her urine that were not prescribed to her but rather borrowed from her daughter. If results of the initial UDT are not as expected, this will affect the decision about whether to initiate opioid therapy. If the UDT is inconsistent once a patient is on chronic opioid therapy, it is important to address the situation with the patient and then make decisions about the course of action.33
Actions may be dictated by the policies in the practice or the treatment agreement. The decision may be to discontinue opioid therapy in the case of illicit drug use, such as heroin or cocaine. In the case where the prescribed medication is not in the urine, it is important to understand the reason. Reasons may include skipping doses, using more than prescribed, and thus running out of medication before obtaining the next prescription or diversion of the opioid. After a discussion about the goals of care (depending on the situation), the NP may decide to continue therapy with more frequent monitoring and reduced time between intervals of prescribing.
Informed consent/treatment agreements
Informed consent outlining the risk, benefits, and expectations should be obtained prior to the initiation of chronic opioid therapy.21 Experts recommend the use of treatment agreements, but there is relatively weak evidence regarding the efficacy of the agreement used to reduce misuse and abuse.21,22,28,42
Some treatment agreements incorporate informed consent that outlines the risks and benefits of therapy. Treatment agreements can include responsibilities of the prescriber and the patient as well as the consequences of nonadherence. Discussion of safe use, adverse reactions, storage, and disposal of opioids can be included in treatment agreements. Examples of treatment agreements are available online.44 Treatment agreements should be tailored to the practice and should be translated into other languages if necessary.
Prescription drug monitoring programs
Prescription drug monitoring programs (PDMP or PMP) are another way to attempt to curb the misuse or diversion of opioids and are one of the recommendations of expert panels.8,22,27 As of December 2013, 48 states and one territory (Guam) had operational PDMPs.45 Prescribers must check the PDMP website before prescribing controlled substances in New York.46 This effort may help, but there are challenges, as individuals can easily cross state lines, and PDMPs are state-specific, varying in function and reliability.
Checking a PDMP can be time consuming for the busy NP, but it is a necessary function to identify patients who may be obtaining medications from more than one source. Dependent on state guidelines, assistive personnel may be able to provide help in accessing the information prior to the patient's appointment.
Choosing the opioid and monitoring therapy
How does the NP decide which opioid to prescribe for chronic opioid therapy? Generally, NPs choose opioids based on personal comfort and formulary access. No robust evidence exists about superior efficacy of extended-release opioids versus short-acting opioids.21 However, extended-release opioids may produce longer periods of stable analgesia, improved sleep, and improved physical function as compared to immediate-release opioids.47 The use of extended-release medication can be considered when a patient is having pain that occurs daily and is not relieved with the use of an immediate-release opioid utilized two to three times daily. Opioids should be started at low doses and titrated carefully.21,22,28 Low-dose opioid therapy is a daily morphine equivalent up to 40 mg, moderate is between 41 and 90 mg morphine equivalent, and high dose is greater than 91 mg of morphine equivalent.22
Patients who require repeated dose escalations should be reassessed for potential reasons for inefficacy of opioids.21 Individuals with persistent pain may experience breakthrough pain, which are periods of increased pain that may occur secondary to activity, but may also occur without a known cause.48 No strong guidelines exist for the treatment of breakthrough pain, but in individuals without any signs of aberrant behavior, the use of an “as-needed” immediate-release opioid may be an option.21 If individuals require “as needed” immediate-release opioids on a routine basis in conjunction with extended-release opioids, assessment is necessary to determine if it is reasonable to increase the dose of the extended-release opioid. It is also important to reassess for any signs of aberrant behavior at each visit.
The use of methadone for pain management should be initiated by experienced pain management clinicians; therefore, methadone may not be a consideration for pain management by primary care NPs.21,22 However, primary care NPs working in areas where individuals do not have easy access to pain specialists may consider working in conjunction with pain specialists to continue methadone once the patient is stabilized on a regimen. Providers should obtain baseline electrocardiograms to evaluate for corrected QT interval prolongation and should be aware of the multiple medication interactions with methadone.22,47
Pharmaceutical manufacturers have responded to the escalation of prescription drug abuse through the development of abuse-deterrent or tamper-resistant formulations of extended-release opioids. These opioids either incorporate physical barriers to prevent crushing the tablet for nasal or I.V. use or contain opioid antagonists, which are released if the medication is tampered.47,49 The FDA issued guidance to industry for future opioid development to ensure that the opioids are more difficult to tamper with and have reduced likeability.50 The emergence of formulations that are abuse-deterrent or tamper-resistant may help in minimizing the abuse of opioids.47,49 However, this does not affect the opioids already on the market, so it is incumbent on the prescriber to understand the different formulations currently available.
So what steps can the NP take to prescribe safely? Choosing abuse-deterrent or tamper-resistant formulations of extended-release opioids should be considered. It is also good to know which opioids are most abused in the area and limit prescriptions for those agents. NPs should dispense the least amount of capsules and tablets possible to decrease potential for overuse.33 For example, it would be better to prescribe 60 extended-release morphine 30 mg tablets to be taken twice daily than to dispense 120 tablets of immediate-release 15 mg morphine.
More frequent monitoring is important at the beginning of opioid therapy for assessment of efficacy, unwanted effects such as oversedation, impaired judgment, and potential problematic behavior.51 Recommended monitoring includes a review of the PDMP or obtaining pharmacy records. The frequency of review depends on the assessed level of risk. Noting the frequency between visits, requests for early refills, performing pill counts, and unannounced UDTs are all monitoring methods that may be important to conduct in the early period of chronic opioid therapy.51
Patient education regarding safe opioid use–including safe administration and management of adverse reactions of opioids–is of great importance. Appropriate education should include information about the use of multimodal therapy to reduce opioid requirements, improve pain control, and improve functioning.52
It is just as important to educate the patient about safe storage and disposal of opioids. Opioids used for nonmedical purposes were obtained free from family and friends 54% of the time and bought/taken from families or friends 14.9% of the time.7 Patients must be counseled to never share opioids and to keep the medications hidden and/or locked to avoid easy access by family members or friends. Downloadable, one-page handouts that discuss safe use, storage, disposal, and comprehensive education for pain management (written for the layperson) should be provided to patients.53,54 Take-back programs are conducted in many communities, and patients should be informed about these programs as a way of disposing their unused medications.55
When to refer
Referral to a pain specialist is recommended for individuals with chronic pain who do not respond to multimodal therapy, request increasing doses of medications, and have a distant history of substance abuse. Individuals who have a past history or actively abuse substances and those with major or untreated psychopathology should be comanaged or managed by a pain specialist.33 A pain specialist consultation is advised for patients on high-dose opioid therapy and is mandated in Washington state.22,56 In some areas of the country, a consultation with a pain specialist may require travel. The pain specialists may provide recommendations for treatment, which can be continued by the NP with further consultations with the pain specialist on an as-needed basis.
NPs have an obligation to assess and manage pain, but not every patient with CNCP is a candidate for opioid therapy. When initiating opioid therapy, it is important that patients understand it is a trial.21 If the patient does not respond to opioids, does not adhere to the treatment plan, or exhibits aberrant behavior (for example, early refills or inconsistent UDTs), then it is appropriate to discontinue opioids. The rate of tapering opioids is dependent on the circumstance, the dose of opioids, and the duration of therapy. There are specific, limited recommendations, and tapering protocols ranging from a taper of 20% to 50% per week.57 Treatment should be individualized and should include clear instructions. A referral for detoxification in a substance abuse treatment program may be necessary in the case of active substance abuse or addiction.57 In these cases, further treatment of the pain should be considered in collaboration with a pain specialist.
Chronic opioid therapy is an option for the treatment of CNCP as part of a multimodal strategy when nonopioid modalities have not been effective. Strategic management of individuals on chronic opioid therapy includes a comprehensive assessment, risk evaluation, and monitoring—all of which are paramount in minimizing the risk of adverse reactions, abuse, and diversion. NPs provide primary care for many individuals with chronic pain and must be competent in assessment and appropriate opioid management.
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