#95131: Prescription Opioids and Pain Management: The Tennessee Guidelines

In 2005 and 2011, hydrocodone and its combinations accounted for 51,225 and 97,183 emergency department visits, respectively, in the United States. Oxycodone and its combinations resulted in 42,810 visits to the emergency department in 2005; this number increased to 175,229 visits in 2011 [7,8]. Visits for nonmedical use of all opioids increased from 217,594 to 420,040 during this six-year period.

Overdose deaths involving prescription opioids are now five times higher than in 2000. From 1999 to 2020, more than 263,000 people died in the United States from overdoses related to prescription opioids [97]. According to the Centers for Disease Control and Prevention (CDC), 91,799 drug overdose deaths were reported in the United States in 2020, of which 68,630 (74.8%) involved prescription or illicit opioids (primarily synthetic opioids such as fentanyl, fentanyl analogs, and tramadol) [91]. Overdose deaths involving just prescription opioids totaled more than 16,000 in 2020, which extrapolates to a 16% increase in prescription opioid-involved death rates from 2019 to 2020.

In 2020, the age-adjusted rate of drug overdose deaths was 28.3 per 100,000 standard population, 31% higher than the rate (21.6) in 2019 [97]. This sharp increase in the rate of overdose deaths was driven largely by overdose and inadvertent poisoning deaths involving synthetic opioids, indicative of a worsening and expanding drug overdose epidemic. From 2019 to 2020, the rate of drug overdose deaths increased for all sex, age, race, and Hispanic-origin groups. The rate of drug overdose deaths involving synthetic opioids (e.g., fentanyl) increased 56% in one year, from 11.4 per 100,000 in 2019 to 17.8 in 2020 [97,98]. Illicitly manufactured fentanyl and fentanyl analogs are highly potent, increasingly available across the United States, and often found in supplies of other drugs.

To assist in monitoring the public health problem associated with prescribed opioids, numerous governmental, nonprofit, and private sector agencies and organizations are involved in collecting, reporting, and analyzing data on the abuse, addiction, fatal overdose, and treatment admissions related to opioid analgesics. In the past decade, federal and state agencies have convened workgroups consisting of subject matter experts, clinicians, and patient representatives to develop clinical practice guidelines for effective and safe opioid prescription drug use.

The CDC Guideline for Prescribing Opioids for Chronic Pain provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care [10]. The guideline recommendations are grouped in reference to three clinical issues: determining when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; assessing risk and addressing harms of opioid use. The 2016 CDC guideline for prescribing opioids is in the process of being updated, with an emphasis on improved communication between providers and patients that enables informed, patient-centered decisions for safe and effective pain care.

Additional opioid prescribing guideline resources for healthcare providers, including clinical tools such as total daily opioid dosage calculators, are maintained by the CDC online at https://www.cdc.gov/opioids/providers/prescribing [99].

In 2011, the state of Tennessee had one of the highest per capita prescription rates for opioids and ranked second in the country for percentage of adult opioid abuse treatment center admissions [92]. According to a 2015 report of opioid abuse in Tennessee, an estimated 212,000 (4.35%) Tennessee adults (18 years of age and older) used pain relievers non-medically in the previous year, the second most prevalent type of drug abuse behind cannabis [93].

From 2014 to 2015, the death rate in Tennessee increased 91% for synthetic opioids (e.g., fentanyl, tramadol), 44% for heroin, and 13% for natural/semisynthetic opioids (e.g., morphine, oxycodone, hydrocodone). The death rate for natural/synthetic opioids was 9.7 per 100,000 population, more than twice the national rate (3.9 per 100,000) [92].

In 2013, the Tennessee legislature, Department of Health, and other agencies came together to address the problem of excessive opioid prescription drug use and the emerging epidemic of drug abuse and overdose. These efforts lead to the creation of a controlled substance database and monitoring program, development of clinical practice guidelines for management of pain and prescription opioid use, and mandated continuing professional education in controlled substance prescribing [94]. There are encouraging signs of progress. From 2016 to 2020, the rate of multiple provider episodes for opioid prescriptions for pain declined from 28.5 per 100,000 residents to 3.5 per 100,000, and opioid prescriptions for pain decreased from 1.98 million dispensed in 2016 to 1.24 million in 2019, representing a decrease of 35.7% [100]. Although deaths from any drug overdose continue to increase (e.g., from 1,776 in 2017 to 2,089 in 2019), overdose deaths from prescription opioids have decreased each year, from a high of 739 in 2016 to 515 deaths in 2019. Reported cases of infants born dependent to drugs with neonatal abstinence syndrome have also declined during this period [94].

For initial management of common, self-limited acute pain syndromes (e.g., acute low back pain), a multimodal approach is recommended, consisting of nonpharmacologic therapies (e.g., heat, massage, physical therapy), a two- to four-week trial of nonsteroidal anti-inflammatory drugs (NSAIDs), and a trial of a non-benzodiazepine muscle relaxant, if pain persists [94]. If, and when, opioids are prescribed for acute pain, clinicians should select the lowest effective dose of immediate-release opioids in a quantity no greater than that needed for the expected duration of severe pain. In most cases, three days or less will be sufficient; more than seven days will rarely be needed [10,94]. However, it is important to note that this recommendation is based on emergency department prescribing guidelines for non-traumatic non-surgical pain [12]. It may be necessary to prescribe for longer periods in patients with acute severe pain.

Perioperative pain should be managed through a combination of targeted methods that includes management of patient expectation and anxiety, activity and mobilization when appropriate, and a trial of non-opioid pain medication for mild-to-moderate pain and opioid medication for severe pain [94]. Postoperative acute or intermittent pain analgesia often requires frequent titration. A 2- to 4-hour analgesic duration with short-acting hydrocodone, morphine, or oxycodone is more effective than extended-release formulations. Short-acting opioids are also recommended in patients who are medically unstable or with highly variable pain intensity [13,14,15].

Unrelieved pain is the greatest fear among people with a life-limiting disease, and the need for an increased understanding of effective pain management is well documented [27]. Although experts have noted that 75% to 90% of end-of-life pain can be managed effectively, rates of pain are high, even among people receiving palliative care [27,28,29,30,31,32,33,34,35,36].

The inadequate management of pain is the result of several factors related to both patients and clinicians. In a survey of oncologists, patient reluctance to take opioids or to report pain were two of the most important barriers to effective pain relief [37]. This reluctance is related to a variety of attitudes and beliefs [27,37]:

Education and open communication are the keys to overcoming these barriers. Every member of the healthcare team should reinforce accurate information about pain management with patients and families. The clinician should initiate conversations about pain management, especially regarding the use of opioids, as few patients will raise the issue themselves or even express their concerns unless they are specifically asked [38]. It is important to acknowledge patients' fears individually and provide information to help them differentiate fact from fiction. For example, when discussing opioids with a patient who fears addiction, the clinician should explain that the risk of addiction is low in the context of opioid use for cancer pain [27]. It is also helpful to note the difference between addiction and physical dependence.

There are several other ways clinicians can allay patients' fears about pain medication:

Encouraging patients to be honest about pain and other symptoms is also vital. Clinicians should ensure that patients understand that pain is multidimensional and emphasize the importance of talking to a member of the healthcare team about possible causes of pain, such as emotional or spiritual distress. The healthcare team and patient should explore psychosocial and cultural factors that may affect self-reporting of pain, such as concern about the cost of medication.

Clinicians' attitudes, beliefs, and experiences also influence cancer pain management, with addiction, tolerance, side effects, and regulations being the most important concerns [27,34,37,39,40,41]. A lack of appropriate education and training in the assessment and management of pain has been noted to be a substantial contributor to ineffective pain management [37,39,41,42]. As a result, many clinicians, especially primary care physicians, do not feel confident about their ability to manage pain in their patients [37,39].

Clinicians require a clear understanding of available medications to relieve pain, including appropriate dosing, safety profiles, and side effects. If necessary, clinicians should consult with pain specialists to develop an effective approach.

Strong opioids are used for severe pain at the end of life [30,34,43,44]. Morphine, buprenorphine, oxycodone, hydromorphone, fentanyl, and methadone are the most widely used in the United States [45]. Unlike non-opioids, opioids do not have a ceiling effect, and the dose can be titrated until pain is relieved or side effects become unmanageable. For an opioid-naïve patient or a patient who has been receiving low doses of a weak opioid, the initial dose should be low, and, if pain persists, the dose may be titrated up daily until pain is controlled.

More than one route of opioid administration will be needed by many patients during end-of-life care, but in general, opioids should be given orally, as this route is the most convenient and least expensive. The transdermal route is preferred to the parenteral route, although dosing with a transdermal patch is less flexible and so may not be appropriate for patients with unstable pain [34]. Intramuscular injections should be avoided because injections are painful, drug absorption is unreliable, and the time to peak concentration is long [34].

The management of chronic pain is among the most prevalent and vexing of clinical issues, a challenge common to physicians and nurses in every clinical discipline of care. As a matter of public health importance, an estimated 116 million adults in the United States suffer from some form of chronic pain [10]. Nonpharmacologic therapy and non-opioid pharmacologic therapy are the preferred first-line therapies for chronic pain. If opioids are used, they should be combined with nonpharmacologic therapy and non-opioid pharmacologic therapy, as appropriate. Clinicians should consider opioid therapy only if expected benefits for pain and function are anticipated to outweigh risks to the patient [10].

Healthcare professionals are obligated to know and apply best practice principles to the use of prescription opioids for management of chronic pain, including knowledge of opioid prescription drug selection and dosage, the associated risks of opioids, approaches to the assessment of pain and function, and appropriate pain management modalities. Pharmacologic and nonpharmacologic approaches should be used on the basis of current knowledge in the evidence base or best clinical practices. Patients with moderate-to-severe chronic pain who have been assessed and treated with an adequate trial of non-opioid therapy or nonpharmacologic pain therapy, without satisfactory pain relief, are considered to be candidates for a trial of opioid therapy [9,10]. Initial treatment should always be considered individually determined and as a trial of therapy, not a definitive course of treatment [11].

The Tennessee Chronic Pain Guidelines enumerate several key principles to follow when initiating opioid therapy [94]. Practitioners should bear in mind that prior opioid therapy alone is not sufficient reason to continue opioids, and reasonable non-opioid treatments should be tried first. When prescription opioids are considered for women of childbearing age, providers should educate the patient about the risks of opioid use during pregnancy, including the risk of physical dependence and withdrawal in the newborn; upon initiation of opioid therapy, the provider should recommend reliable contraception. A urine drug test (UDT) should be performed before initiating any opioid or benzodiazepine during pregnancy [94]. A thorough clinical examination, including appropriate laboratory testing and other elements supporting the plan of care, should be documented in the medical record. Patients shall not be treated by the use of controlled substances through telemedicine.

According to the American Society of Interventional Pain Physicians, before starting opioid therapy, clinicians must take certain basic steps to prevent opioid abuse: distinguish individual opioid abuse risk factors; screen patients' potential for addiction and abuse during their initial visit; categorize patients in accordance with their level of risk and implement an appropriate level of monitoring; and refrain from judgments before a thorough assessment. Combining the above strategies with point-of-care urine drug testing as a confirmatory tool have been shown to contribute significantly to the identification of inconsistencies.

(https://www.painphysicianjournal.com/current/pdf?article=NDIwNA%3D%3D&journal=103 Last Accessed: September 21, 2022)

Level of Evidence: Expert Opinion/Consensus Statement

Before deciding to prescribe an opioid analgesic, clinicians should perform and document a detailed patient assessment that includes [1,94]:

The initial evaluation is intended to establish a current diagnosis that justifies the need for opioid medication. After this determination is made, it is important to assess the patient's risk for drug misuse and develop and document a treatment plan, including a discussion of treatment goals.

The initial opioid prescription is preceded by a written informed consent or "treatment agreement" [1]. This agreement should address the rationale for and appropriate use of a controlled medication and the mechanism of action, expected benefit, and limitations of therapy. It should also provide information regarding potential negative effects of controlled medication, including side effects, tolerance and/or physical dependence, drug interactions, motor skill impairment, limited evidence of long-term benefit, misuse, addiction, and drug diversion. Informed consent documents should include information regarding the risk/benefit profile for the drug(s) being prescribed and common-sense rules for using controlled medications safely. The prescribing policies should be clearly delineated, including the number/frequency of refills, early refills, and procedures for lost or stolen medications.

The treatment agreement also outlines joint physician and patient responsibilities. The prescriber's responsibility is to address unforeseen problems and prescribe scheduled refills. The patient agrees to using medications safely, refraining from "doctor shopping," and consenting to routine UDTs. Included is the expectation that a patient will inform the provider if she wishes to avoid unintended pregnancy and if she becomes pregnant. The Tennessee practice guidelines recommend that the practitioner obtain a signature indicating that any woman who wishes to become or is at risk to become pregnant has been educated about the risks and benefits of opioid treatment during her pregnancy [94]. When there is a change or discontinuation of opioid treatment, the reasons should be documented. Agreements may also include sections related to follow-up visits, monitoring, and safe storage and disposal of unused drugs.

The Tennessee Department of Health provides a sample Informed Consent/Controlled Substance Agreement and Patient Agreement/Treatment Attestation form in the Appendix of the Chronic Pain Management Guidelines [94].

Opioid therapy for chronic pain should be presented as a trial for a pre-defined period (e.g., ≤30 days). The goals of treatment should be established with all patients prior to the initiation of opioid therapy, including reasonable improvements in pain, function, depression, anxiety, and avoidance of unnecessary or excessive medication use [1,10]. It should be emphasized to the patient that the primary goal is to improve function and reduce pain, not necessarily to eliminate pain entirely. The treatment plan should describe therapy selected, progress measures, and other diagnostic evaluations, consultations, and therapies. The plan should establish realistic goals that can be assessed on follow-up. A commonly used assessment tool is the three-item PEG assessment scale [94]:

In opioid-naïve patients, one should start at the lowest possible dose and titrate to effect. Dosages for opioid-tolerant patients should always be individualized and titrated by efficacy and tolerability [1,10]. When initiating opioid therapy for chronic pain, clinicians should select an immediate-release, short-acting opioid instead of an extended-release/long-acting opioid formulation [10,94]. Additional principles, emphasized by the Tennessee Practice Guidelines, include [94]:

The need for frequent progress and benefit/risk assessments during the trial should be included in patient education. Patients should also have full knowledge of the warning signs and symptoms of respiratory depression. The risk of overdose deaths starts at 40 mg MED per day in opioid-naïve patients, and the highest risk is in the first two weeks of therapy [94]. Prescribers should carefully reassess evidence of benefits and risks when increasing the dosage to ≥50 mg MED per day. Decisions to titrate dose to ≥90 mg MED per day should be avoided or carefully justified [10].

According to CDC data for 2020, there were 91,799 deaths due to drug overdose nationwide, of which 68,630 resulted from a poisoning or overdose involving opioids, including more than 13,000 deaths involving a prescription opioid.

Naloxone is a prescription opioid antagonist approved by the FDA for use in reversing the effects of an overdose involving opioids. The medication works by blocking opioid receptors to reverse suppression of respiratory drive caused by excessive opioid effect. Naloxone is available in multiple dosage and routes of administration, which include intramuscular, intravenous, and intranasal formulations [94].

In the outpatient setting, patients may be at risk for an overdose because of factors related to opioid dosage and usage, or because of pre-existing conditions that can negatively impact tolerance to opioids. Among patients to consider at risk are those who [94]:

The Tennessee Chronic Pain Guidelines recommend that clinicians should incorporate into the management plan strategies to mitigate risk, including the offer of naloxone for use by patients (or family members) when factors that increase the risk for opioid overdose are present [94]. The best way to ensure access to naloxone is to simultaneously prescribe the medication at the same time a prescription for an opioid is written. It is recommended that prescribers provide a prescription for naloxone hydrochloride or another drug approved by the FDA for the complete or partial reversal of an opioid event to a patient at risk. A licensed healthcare practitioner in Tennessee may prescribe naloxone for a patient, when acting in good faith and exercising reasonable care, both with an opioid prescription or at any time following the prescription of an opioid [94].

When the decision is made to continue opioid treatment for chronic pain, care providers should regularly assess clinical progress and monitor the patient for signs of drug abuse, misuse, or diversion. The Tennessee practice guidelines emphasize that a single provider should handle all chronic opioid therapy and all prescriptions should be filled by a single pharmacy. Opioids should be used at the lowest effective dose. A provider should not use more than one short-acting opioid concurrently. Patients who require opioid doses of 120 mg MED or greater should be referred to a pain specialist for consultation and/or management. An unannounced UDT should be done twice every year, at a minimum [94].

Prescribers should be knowledgeable of federal and state opioid prescribing regulations. Issues of equianalgesic dosing, close patient monitoring during all dosage changes, and cross-tolerance with opioid conversion should be considered. If necessary, treatment may be augmented, with preference for non-opioid and immediate-release opioids over long-acting/extended-release opioids. A protocol for tapering the opioid should be implemented when the drug is no longer needed [16].

Clinical follow-up at regular intervals should include reassessment for changes in pain character and intensity, general health, and function [1]. This can include input from family members and/or the CSMD. During the initiation phase and following any changes to the dosage or agent used, patient contact should be increased. At every visit, the clinical response to therapy should be discussed and documented in the medical record, in reference to the "5 A's" [1,23,94]:

Signs and symptoms that, if present, may suggest a problematic response to the opioid and interference with the goal of functional improvement include [24]:

The decision to continue, change, or terminate opioid therapy is based on progress toward treatment objectives and absence of adverse effects and risks of overdose or diversion [1]. Satisfactory therapy is indicated by improvements in pain, function, and quality of life. Brief assessment tools to assess pain and function may be useful, as may UDTs. Treatment plans may include periodic pill counts to confirm adherence and minimize diversion.

Successful pain management or mitigation of problems that arise often require consultation or patient referral to a pain, addiction, or mental health specialist. Clinicians who prescribe opioids should become familiar with opioid addiction treatment options (including licensed opioid treatment programs for methadone and buprenorphine) if referral is needed [1].

Ideally, providers should be able to refer patients with active substance abuse who require prescription pain treatment to an addiction professional or specialized program. In reality, these specialized resources are scarce or non-existent in many areas [1]. Therefore, each provider will need to decide whether the risks of continuing opioid treatment for a patient using illicit drugs outweigh the benefits in terms of pain control and improved function [48].

As noted, documentation is a necessary aspect of all patient care, but it is of particular importance when opioid prescribing is involved. All clinicians should maintain accurate, complete, and up-to-date medical records, including all written or telephoned prescription orders for opioid analgesics and other controlled substances, all written instructions to the patient for medication use, and the name, telephone number, and address of the patient's pharmacy [1]. Good medical records demonstrate that a service was provided to the patient and that the service was medically necessary. Regardless of the treatment outcome, thorough medical records protect the prescriber.

Patients and caregivers should be counseled regarding the safe use and disposal of opioids. As part of its mandatory Risk Evaluation and Mitigation Strategy (REMS) for extended-release/long-acting opioids, the U.S. Food and Drug Administration (FDA) has developed a patient counseling document with information on the patient's specific medications, instructions for emergency situations and incomplete pain control, and warnings not to share medications or take them unprescribed [16]. A copy of this form may be accessed online at https://www.fda.gov/media/86281/download.

When prescribing opioids, clinicians should provide patients with the following information [16]:

There are no universal recommendations for the proper disposal of unused opioids, and patients are rarely advised of what to do with unused or expired medications [49]. According to the Office of National Drug Control Policy, most medications that are no longer necessary or have expired should be removed from their containers, mixed with undesirable substances (e.g., cat litter, used coffee grounds), and put into an impermeable, nondescript container (e.g., disposable container with a lid or a sealed bag) before throwing in the trash [50]. Any personal information should be obscured or destroyed. The FDA recommends that certain medications such as oxycodone/acetaminophen (Percocet), oxycodone (OxyContin tablets), and transdermal fentanyl (Duragesic Transdermal System), may be flushed down the toilet instead of thrown in the trash [50]. Patients should be advised to flush prescription drugs down the toilet only if the label or accompanying patient information specifically instructs doing so.

The American College of Preventive Medicine has published best practice recommendations designed to avoid diversion of unused drugs and educate patients regarding drug disposal [49]:

The state of Tennessee has developed two types of disposal activities designed to control access and promote safe, convenient, and responsible disposal of prescription drugs [94]. The first is a system of permanent prescription drug collection boxes located within law enforcement agencies (in compliance with DEA regulations) where community members can safely deposit drugs in a secure manner. The goal is to establish at least one permanent prescription drug collection box in all 95 counties of the state. The second activity involves community one-day "take-back" events wherein the public is encouraged to discard unwanted and outdated medications including prescription drugs from their homes. These events serve to raise public awareness of the prescription drug epidemic and encourage the use of local permanent disposal sites available year-round. A map showing the locations of permanent drug collection boxes can be found online at https://tdeconline.tn.gov/rxtakeback.

The decision to modify or terminate prescription opioid use is based on clinical progress and a physician-patient discussion of the realized benefits or adverse effects. Among the reasons to taper or discontinue an opioid regimen are resolution of the condition causing pain, intolerable side effects, inadequate analgesia, lack of improvement in quality of life despite dose titration, deteriorating function, and significant aberrant medication use [1,10].

The decision to discontinue opioids carries the potential risk for troublesome withdrawal symptoms. Common symptoms of opioid withdrawal syndrome include nausea, vomiting, headache, abdominal pain, myalgia, and sweating. Although discomforting, the syndrome is usually not fatal, unlike benzodiazepine withdrawal. While low-dose and brief duration opioid regimens may not require weaning of the dosage, clinicians should always consider the need for a safely structured tapering protocol. Withdrawal may be managed by the prescribing physician or by referral to a pain or addiction specialist.

The Tennessee Department of Health suggestions for a tapering protocol are [94]:

Patients should be reassured that opioid discontinuation is not the end of treatment; continuation of pain management will be undertaken with other modalities through direct care or referral.

As a side note, cannabis use by chronic pain patients receiving opioid therapy has traditionally been viewed as a treatment agreement violation that is grounds for termination of opioid therapy. However, some now argue against cannabis use as a rationale for termination or substantial treatment and monitoring changes, especially considering the increasing legalization of medical use at the state level [48].

For patients who are not proficient in English, it is important that information regarding the risks associated with the use of opioids and available resources be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter. In any case in which information regarding treatment options and medication/treatment measures are being provided, the use of an interpreter should be considered. Print materials are also available in many languages, and these should be offered whenever necessary.