Guidelines, Recommendations, and Principles for Prescribing Opioids (FL INITIAL Autonomous Practice - Pharmacology)

Opioid use and addiction to these controlled substances is currently considered a global crisis. The opioid use epidemic has increasingly gotten worse. Providers are trying to navigate safely prescribing opioids when necessary and learning more about the risk for addiction and diversion.

The Iowa Administrative Code (IAC) 655, chapter 7.6, discusses eight key points regarding the standards of practice for advanced registered nurse practitioners (ARNPs) surrounding controlled substances (IAC, 2019). 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 is not provided, the ARNP must document the reason. Fifth, the ARNP must maintain an active Drug Enforcement Administration (DEA) 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 opioids are prescribed in dosages that another reasonably prudent ARNP would not prescribe 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 Centers for Disease Control and Prevention's (CDC's) guidelines for prescribing opioids for chronic pain.

Also, IAC 655, chapter 7.7, states that the ARNP should utilize the prescription drug monitoring program (PDMP) before prescribing or dispensing an opioid (IAC, 2019). 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.

Prescription Paper

It is pertinent to understand the terms and definitions related to substance use and abuse.

Substance abuse is the "intentional use of the opioid for a nonmedical purpose, such as euphoria or altering one's state of consciousness" (Kalkman et al., 2022).

Addiction is a "pattern of continued use with experience of, or demonstrated potential for, harm" (Kalkman et al., 2022).

To appropriately prescribe opioid analgesics, pain should be alleviated, and the risk of use disorder and toxicity should be minimized while implementing safeguards that prevent or reduce the occurrence of drug diversion (Preuss et al., 2023).

"Alcohol use disorder (AUD) is a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences" (American Psychological Association [APA], 2022).

Cannabinoid products are used either as the natural marijuana plant or isolated from the constituents of the marijuana/hemp plant.

A controlled substance is a drug or other substance the government tightly controls because it may be abused or cause addiction.

The Drug Abuse Screening Test (DAST-10) is a 10-question screening tool administered by a clinician or can be self-administered to detect substance abuse.

DAST-20 is a 10-item, yes/no self-report instrument designed to provide a short tool for clinical screening and treatment evaluation that can be used with adults and older youth.

Iatrogenic harm is unintentionally induced by a physician or surgeon, medical treatment, or diagnostic procedures (Merriam-Webster, n.d.).

Opioid-tolerant patients are those taking, for at least one week, ≥ 60 milligrams (mg) oral morphine a day, ≥ 25 micrograms (mcg) transdermal fentanyl per hour, ≥ 30 mg oral oxycodone a day, ≥ 8 mg oral hydromorphone a day, ≥ 25 mg oral oxymorphone a day, ≥ 60 mg oral hydrocodone a day, or an equivalent dose of another opioid (Food and Drug Administration [FDA], 2009).

An example of inappropriate opioid analgesic prescribing is inadequate, continued, or excessive prescribing despite evidence of the lack of effective opioid analgesic treatment (Preuss et al., 2023).

Misuse is "opioid use contrary to the directed or prescribed pattern of use, regardless of the presence or absence of harm or adverse effects" (Kalkman et al.,2022).

Naloxone (Narcan®) or Kloxxado® is an opioid antagonist that can quickly reverse an overdose of opioid drugs (National Institute on Drug Abuse [NIDA], 2022).

The Opioid Risk Tool (ORT) is over 20 years old and is a self-report tool to assess for opioid use disorder.

Pain neuroscience education (PNE) teaches about pain mechanisms, causing the brain to stop overreacting and becoming constantly hyper-stimulated at the cerebral cortex level. This, in turn, reduces cerebral threat perception, which decreases the activation of pain systems in the brain. PNE is for pain like fibromyalgia.

"Pain is an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage" (Raja et al., 2020).

Acute pain duration is usually < one month.

Sub-acute pain duration is around 4-12 weeks.

Chronic pain duration is > three months.

Acute, chronic pain is when a "flare-up" of "old" pain is usually due to a new insult to an old injury.

Neuropathic pain- sometimes called nerve pain. This is caused by the somatosensory nervous system's primary lesion(s).

Visceral pain is induced by organs, such as the gallbladder, stomach, or bladder (a deep aching).

Nociceptive pain is normally expected from an injury to tissues and inflammation. Activation and sensitization of the nociceptive pain pathway by the body's inflammation mediators, such as bradykinins (usually sharp, caused by movement or intermittent to constant sharp aching), are released at the injury site.

Computerized statewide PDMP's differ in each state and country.

Prescription diversion is giving, selling, or loss due to theft of all or part of a prescription for controlled medications to anyone other than for whom it is prescribed.

Urine drug test (UDT)- tests for the presence of substances in the urine.

Screener and Opioid Assessment for Patients with Pain (SOAPP)- this helps determine monitoring guidelines for patients taking opioids.

The Diagnostic and Statistical Manual of Mental Disorders or DSM-5 criteria for substance use disorder is a maladaptive pattern of substance use leading to clinically significant impairment or distress (Hartney, 2023).

The DSM-5 criteria for the diagnosis of opioid use disorder include the following:

• Opioids are often taken in more significant amounts or longer than intended.
• There is a persistent desire or unsuccessful efforts to reduce or control opioid use.
• A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
• Craving, or a strong desire to use opioids.
• Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
• Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
• Important social, occupational, or recreational activities are given up or reduced because of opioid use.
• Recurrent opioid use in situations in which it is physically hazardous.
• Continued use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by opioids (APA 2022).

Tolerance is either one of the following:

1. A need for markedly increased amounts of opioids to achieve intoxication or the desired effect
2. Markedly diminished effect with continued use of the same amount of an opioid (APA 2022)

Either of the following may be manifestations of withdrawal:

1. The characteristic opioid withdrawal syndrome
2. The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms (APA 2022)

The CDC has implemented clinical practice guidelines and recommendations. The guidelines include the following:

1. Acute, subacute, and chronic pain needs to be appropriately assessed and treated independent of whether opioids are part of a treatment regimen.
2. Recommendations are voluntary and are intended to support, not supplant, individualized, person-centered care. Flexibility to meet a specific patient's care needs and clinical circumstances is paramount.
3. A multimodal and multidisciplinary approach to pain management, attending to the physical health, behavioral health, long-term services and supports, and expected health outcomes and well-being of each person is critical.
4. Special attention should be given to avoid misapplying this clinical practice guideline beyond its intended use or implementing policies purportedly derived from it that might lead to unintended and potentially harmful consequences for patients.
5. Clinicians, practices, health systems, and payers should vigilantly attend to health inequities; provide culturally and linguistically appropriate communication, including communication that is accessible to persons with disabilities; and ensure access to an appropriate, affordable, diversified, coordinated, and effective nonpharmacologic and pharmacologic pain management regimen for all persons (CDC, 2022, p.1).

CDC's recommendations include the following:

Recommendation 1

Maximize the use of nonpharmacologic and nonopioid pharmacologic therapies for acute pain. Consider the use of opioids for acute pain only if the benefits outweigh the risks and discuss that with the patient (CDC, 2022).

Recommendation 2

Maximize the use of nonpharmacologic and nonopioid pharmacologic therapies for subacute and chronic pain. Consider the use of opioids for acute pain only if the benefits outweigh the risks and discuss that with the patient. Make an appropriate selection of opioids and dosage (CDC, 2022).

Recommendation 3

Initially, prescribe immediate-release instead of long-acting opioids (CDC, 2022).

Recommendation 4

Initially, prescribe the lowest effective dosage for opioid-naïve patients. When increasing the dosage, do not exceed the level likely to yield diminishing returns (CDC, 2022).

Recommendation 5

For patients already on opioid therapy, carefully weigh the benefits and risks when changing the opioid dosage. If the benefits do not outweigh the risks, optimize other therapies and work with the patient to taper to lower dosages or discontinue opioids if appropriate. Do not stop opioids abruptly unless there is an overdose (CDC, 2022).

Recommendation 6

Only prescribe the amount for the expected duration of acute pain (CDC, 2022).

Recommendation 7

Evaluate the benefits and risks within 1-4 weeks of starting opioids and regularly after that.

Recommendation 8

Evaluate and discuss the risks of opioids with the patient before and during therapy. Work with the patient to use a plan that mitigates risks, including naloxone. Mitigation strategies may include:

• Ask patients about their drug and alcohol use
• Use validated tools
• Consult with behavioral specialists to screen and assess mental health and substance use disorders
• Use PDMP data and toxicology screening as appropriate (CDC, 2022)

Recommendation 9

For all pain levels, initially and periodically review the history using PDMP for patients on opioids (CDC, 2022).

Recommendation 10

For subacute and chronic pain, consider the use of toxicology testing (CDC, 2022).

Recommendation 11

Use extra caution when prescribing opioid pain medication and benzodiazepines (CDC, 2022). 

Recommendation 12

Treating opioid use disorder should be offered or arranged. Detoxification increases the risk of relapse and overdose. FDA-approved medications for the treatment of opioid use disorder include the following:

• Buprenorphine
• Methadone
• Naltrexone 

The Substance Abuse and Mental Health Services Administration (SAMHSA) is a good resource regarding qualifications and the process for prescribing buprenorphine (CDC, 2022).

Understanding the diversion of drugs helps to see the bigger picture in the epidemic of opioid and other controlled substance prescribing environments. There is a greater likelihood that providers will alleviate it at the primary care level if they know the facts and follow the FDA, CDC, and Veteran Affairs (VA's) recommendations with a higher degree of care and discernment.

With any patient, there can be a risk of addiction (even with pain present), diversion, abuse, or misuse of controlled substances. While unfortunate, the actions of some actors and the epidemic of complex medico-legal disasters have outweighed the patients' needs due to legitimate pain and mental health. Stringent guidelines and laws have been implemented to stem the tide of illicit activities; this has been successful, but in a limited way (Manchikanti et al., 2022).

Providers willing to comply with all the detailed rules and regulations must avoid seeming untrusting or suspicious as they fulfill their obligation to "do no harm." According to Goldstick et al. (2022), providers have reacted to the extreme in the face of very restrictive guidelines published by the CDC in 2016. The CDC did not intend for this reaction. Thus, they wrote new guidelines in 2019, which include the warning not to overreact and thereby harm patients (iatrogenic harm) who are justifiably in need (Dowell et al., 2022; Salvatore et al., 2022).

According to Manchikanti et al. (2022), the 2016 CDC opioid guidelines were aimed at primary care providers. However, many state boards mandated them by law, resulting in tremendous needless suffering and exacerbating the illicit opioid epidemic with the causation of unnecessary deaths. These guidelines not only restrict opioid prescriptions but also have inadvertently restricted interventional techniques to reduce access and send patients to the streets for illicit opioids.

Providers were concerned about being on the right side of the law and were attempting to protect their hard-earned licenses. Providers already have the task of trying to discern "real need" from manipulation attempts to gain controlled substances for diversion (Preuss et al., 2023). Provider trust may be an issue when a provider requires a patient to sign a patient responsibility contract allowing UDT and pill counting. UDT is put in place to identify the need to work with a patient who is using other (illegal) drugs and, at the same time, to find that the patient is indeed consuming at least some of the prescribed medications. Patients may be "self-medicating" with other illegal controlled substances, such as street drugs, which may be dangerous. These patients will need help to discern this and a medication change to eliminate the need to self-medicate. Pill counting is a time-consuming measure that may be a relatively accurate way to determine whether a patient has been diverting medications. Still, it is not a perfect way to assess risks alone (Gill et al., 2022).

Studies are needed to design newer tools, and many computer-assisted tools were in development in 2022 but are not available to the providers at the clinic or community level (Wei-Hsuan et al., 2022). Hospitals are equipping themselves against diversion perpetrated by staff using computer-driven algorithm software, which can be built into the medication dispensing workstations (Shaw, 2022).

Regarding the prescribing, monitoring, and discontinuing of controlled medications, communication and education with the patients must be performed and documented to maintain strict conformation to states' requirements. During your initial patient-provider communications, you should touch on the pain your patient describes and which medications are best for reducing and relieving that type of pain.

Education should include the side effects, dosage, safety information (such as safe, locked storage), and signs of overdose. The CDC encourages that naloxone be prescribed with dosage instructions when opioids are prescribed. Overdose of naloxone is rare, but depending on the level of opioid dose, repeated consecutive doses could be uncomfortable for the habituated patient (Dowell et al., 2022). The patient and family members or caregiver should be warned to call 911 immediately after a naloxone dose, as the dose should be managed moment-by-moment by a medical professional as soon as possible.

After the clinician determines that a controlled substance will be prescribed, there is yet more work for the provider to do. Due to the unintended tragic situation caused by the industry's overreaction to the CDC 2016 guidelines, Manchkanti et al. (2022) reported increased illegal drugs for pain and (presumably) mental health issues. There was a concurrent increase in suicides among people with severe chronic pain issues when providers discontinued chronic controlled substances. Many tapering/weaning-off plans were either unsupported or not implemented. Provider-to-patient trust became an issue.

First, discovering the patient's personal, religious, social, and cultural pain constructs are legitimate assessments for pain management. Assessing the patient's cognitive ability as it relates to expressing pain and understanding issues to avoid is also particularly important. With a nonverbal patient, the provider must look for signs and question family members about the patient's pain history. All these things are part of patient-provider communication.

The patient sets pain goals to discover a place to begin tapering off the medications without leaving the patient in severe pain or with severe mental health issues. Pain goals may include:

• Getting the most pain relief with the least amount of side effects.
• Improving the quality of life in the long term as well as the short term.
• Safely returning to work without side effects of pain medications.

The provider should also be alert to psychological improvements and quality of life changes. It is also a tool that the clinician can use to teach that it may not be possible to eliminate all pain (as a goal) in a patient's body. Sometimes, especially in subacute or chronic pain, the best a patient and provider can hope for is to keep pain to a reasonable level (a goal chosen by the patient) and remediate it with nonpharmacological means. Decisions between the patient and the provider must be made about whether weaning off the drug is the goal or if specialized medical/mental healthcare is the goal. Prescriptions can be written for temporary relief while the patient gets established with a specialist in the field they require. The patient must be taught about medication safety and keeping controlled substances at home. The danger of child overdose cannot be stressed strongly enough. In a retrospective study by Champagne-Langabeer et al. (2022), during the three years ending in 2017, almost 60,000 children were in emergency departments (ED) in the United States for opioid use and overdoses. The mean age was 11.3, and the greater part were girls. In addition, most of the children were from the South. Sadly, 68.5 percent of these visits were from opioid overdoses. Overall, infants were in the second-largest opioid accident group to appear in EDs across the United States during this period. Over 9000 children have died since the turn of the century because of opioid accidents (Champagne-Langabeer et al., 2022). The rate of prescription opioid overdose among adolescents has also been increasing in recent years. In 2022, there were an estimated 1,800 deaths from prescription opioid overdoses among adolescents; this number is more than double the number of deaths from prescription opioid overdoses among adolescents in 2002. Locked, safe, and out-of-reach controlled substance storage in the home is critical. These statistics also indicate the need for naloxone prescriptions with opioid medications for patient and family safety (NIDA, 2023).

Theft of opioids and other controlled substances is a major way drugs are diverted from their intended use. Hence, a locked cabinet is the best solution. Parents are not often willing to believe their minor children or other family members in an extended family household would steal medications; however, one study noted 50 percent of 12 to 17-year-olds have reported they stole medications from family members in the previous 12 months (NIDA, 2022). According to the NIDA, an estimated 2.5 million adolescents aged 12 to 17 used prescription opioids for nonmedical purposes in 2022; this number has been steadily increasing in recent years, and it is now more than double the number of adolescents who used prescription opioids for nonmedical purposes in 2002 (SAMHSA, 2022).

One study found that 10.6% of adults aged 18-25 reported using a prescription pain reliever without a prescription in the past year. Of these, an estimated 2.1 million adults reported having obtained their prescription pain relievers from a friend or family member, and an estimated 500,000 adults reported having obtained their prescription stimulants from a friend or family member. Theft by parents of children prescribed controlled substances for various conditions, from ADHD to pain, also occurs (SAMHSA, 2022). Pharmacy misappropriation, robbery of legitimate drug transport from manufacturers, stealing prescription ordering supplies from medical offices, and stealing from hospitals and other health facilities by healthcare workers and others, including hospices, are occurring. The patients from all the facilities mentioned above are part of the diversion picture. Since diversion may also come from inadequate disposal of "leftover drugs," there are ways to prevent this. We must not overprescribe to satisfy the "as needed" quantities. Our patients react to leftover, labor, time, and financially intensive medications by "saving" them for the future; this becomes problematic if used without supervising the overall health picture shared with others. Now, the patient is an illicit provider and an illegal pharmacy. A child or a pet could ingest that medication, or the medication could be stolen, used, or sold. Proper disposal of these leftover medications becomes imperative. DEA Drug Take Back boxes are at pharmacies nationwide. For the search for year-round take-back locations, please see the following link.

Using the criteria set for substance abuse disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), providers are expected to determine whether a patient will likely abuse, divert, or get addicted to a controlled substance prescription. Multiple screening tools are available for identifying drug or alcohol abusers, such as ORT (attachment A) and SOAAP (attachment B). DAST-10 and DAST-20 are designed to identify drug or alcohol abuse in adults and adolescent abusers, respectively.

These tools are primarily patient self-screening tests that can also be administered by trained nurses and are intended to be used simultaneously with the providers' advanced education and intrinsic good judgment. It is unclear if the substance abuser would be honest and forthcoming while filling out one of these tools. That is why there are several red flags you can watch for that will be covered later.

A PDMP is an electronic database that tracks controlled substance prescriptions in a state. They can provide health and legal authorities with timely information about providers' prescribing and patient behaviors that contribute to the epidemic and facilitate a nimble and targeted response (CDC, 2021). PDMPs track controlled substance prescriptions from physicians, nurse practitioners, and physician assistants. They also track pharmacists who fill controlled substance prescriptions.

According to Niculescu et al. (2019), pain is so real that there are genetic serum biomarkers for its presence and severity. Sadly, they report that suicidality shares some markers with severe pain. Pain has been described throughout human history as an enemy, a threat to sanity, and a lover. There are many ways to accept pain occurring in our bodies, but accepting pain in others is much more difficult. We tend to minimize other people's pain, and according to studies, we are minimizing based on our subjective criteria, with little thought for the patient's subjective report. Depending upon our biases, we may even judge pain in others by their age, gender, apparent financial status, and racial appearance (Keister et al., 2021). As each patient's pain is different and specific to them, there is no one-size-fits-all dosage of pain medication. Pain tolerance differs for each person and changes throughout the lifespan (Mullins et al., 2022).

There is a syndrome in patient management called opioid-induced hyperalgesia (OIH), where the medication causes more pain than it relieves. Hyperalgesia is the body feeling a heightened level of pain. Allodynia is the sensation of pain related to a stimulus that ordinarily does not cause pain, such as a light touch or a cool breeze. Allodynia and hyperalgesia can also be leftovers of OIH. The best thing you can do for OIH is reduce the level of pain medication and titrate it to a similar morphine milligram equivalent (MME) in another opioid. The treatment for hyperalgesia is an N-methyl-D-aspartate (NMDA) receptor agonist such as methadone or ketamine, and for allodynia, pregabalin or another nerve pain medication. People at high risk for allodynia are migraine sufferers, with women at greater risk than men. The culprit for allodynia for both men and women is nerve damage.

It is reported in several studies that there is a bias toward prescribing opioid pain relievers to people who are married, white, and of a mature (50-65 years) age as a preference (Keister, 2021). Dr. Carmen Green reports that women of color are unable to have their pain treated or even assessed properly (HealthyWomen, 2020). Even in the case of sickle cell disease (SCD), a widely understood disease process that causes pain by its very mechanism, it is undertreated and given less than sterling care. With more than 90% of SCD patients in America being of African descent, it is an easy-to-study bias phenomenon (Marr et al., 2022). However, Boring et al. (2022) report that there is a bias that women and people of color overrate their pain. Still, their study shows that this is not true, showing that women and people of color often minimize their pain due to fears of not being believed and that we all discount or minimize the pain of others. This is a complex issue psychologically, but it may be sufficient to be aware of our biases and do our best to realize that other people are more likely to tell the subjective truth about their pain (Boring et al., 2022).

You will encounter two common situations at least once and probably much more often in primary care.

The selected medications below are listed for your information. However, controlled pain medications are not the chosen treatments according to the CDC, the FDA, and the VA. These agencies recommend that nonopioid and nonpharmacological therapies be used for sub-acute (flare-ups) and chronic pain treatment (Dowell et al.,2022; Department of Defense, 2022). Nonpharmacological treatments could be said to fall into five groups, which include:

• Metabolic: Dietary supplements, herbs, vitamins and minerals, weight loss.
• Stress Reduction: Yoga, meditation, acupressure, massage.
• Device Assisted: Acupuncture, transcranial or direct magnetic stimulation, neurofeedback, chiropractor.
• Exercise: Tai Chi, qigong, stretching, physical therapy, PNE with physical therapy.
• Psychosocial: PNE, support groups, volunteering.

Some of these nonpharmacological areas overlap and are used in combination with each other and with noncontrolled and controlled pain relief medications. Patients should be strongly encouraged to participate in one or more as this is more effective for increasing the quality of life and decreasing awareness of pain and discomfort than medications alone (CDC, 2022; VA, 2019).

Antiepileptics

Gabapentin or Neurontin is used for nerve pain and as an antineuralgic, anticonvulsant, and muscle relaxant. Off-label uses are diabetic neuropathy, trigeminal neuralgia, fibromyalgia, and complex regional pain syndrome. Pregabalin or Lyrica is an antiepileptic used for nerve pain such as fibromyalgia, post-herpetic neuralgia, diabetic neuropathies, and spinal cord injuries resulting in pain.

Antidepressants

Common antidepressants include serotonin-norepinephrine reuptake inhibitors (SNRIs), which include duloxetine, venlafaxine, and Pristiq®, and tricyclic antidepressants (TCAs), which include amitriptyline, clomipramine, desipramine, imipramine, and nortriptyline. According to Ferreira et al. (2023), antidepressant medications are used for several pain issues. In a study of over 25,000 people (156 different trials), Ferreira et al. (2023) discovered that chronic pain may present as fibromyalgia, migraine headaches, chronic back pain, post-orthopedic surgery pain, irritable bowel syndrome, and neuropathic pain. SNRIs gave moderate relief in just 26% of cases; 74% of the trials reviewed showed little or inconclusive evidence of efficacy, whereas TCAs were shown to be moderately effective in neuropathic pain only. These antidepressant drugs were not interchangeable for any type of pain. Selective Serotonin Reuptake Inhibitors (SSRIs) were not shown to be effective in the trials.

NSAIDS

Non-selective NSAIDs are for mild to moderate pain and inflammation.

• Diclofenac (Voltaren®) 50 mg three times a day (TID) PO is the common prescription. Side effects include indigestion, gastrointestinal upset and cramps, and fluid retention. It is also available over the counter as a topical medication for arthritic pain.
• Ibuprofen (Advil®/Motrin®)- this drug is available in many forms and is sometimes included in opiate formulations (oxycodone/ibuprofen). Side effects include indigestion, gastrointestinal upset, cramps, and dizziness.
• Indomethacin, ketoprofen, ketorolac, meloxicam.
• Celecoxib.

Antipyretic analgesics

Acetaminophen is not an anti-inflammatory medication; there is no blood thinning effect or gastrointestinal upset as seen in NSAIDs, and it is often used for mild, moderate, or severe pain, as a single drug or in combination with opioids or other drugs such as caffeine, aspirin, dihydrocodeine, butalbital.

Controlled pain medications are commonly used in pain management and psychiatry.

Rules and regulations for controlled substances vary by state and federal law in the United States. Schedule II-controlled substance prescriptions cannot be refilled and expire after six months. Schedule III or IV prescriptions may not be filled or refilled more than six months after the written date or refilled more than five times, whichever comes first (Queremel Milani & Davis, 2023). Schedule V controlled substances may be refilled as authorized. Laws may vary by state. A complete list of scheduled drugs is available at Drugs of Abuse: A DEA Resource Guide.

Schedule I 

The list of Schedule I substances includes marijuana, heroin, and lysergic acid diethylamide (LSD). We will discuss only the one currently being used for pain medication.

There are 38 states where all forms of medical marijuana are legal (Anderson & Rees, 2023); this is a controversial moment in the history of marijuana legalization by the states because the drug is still classified as Schedule I by the federal government. The VA and Federal Bureau of Prisons do not allow marijuana for their patients. If they have marijuana show up on a drug test, they will be penalized (VA, 2016). There is currently no consensus on what or when a change might be made, as marijuana could be reclassified (rescheduled), or perhaps as it is legal for recreational use in many states, it might be decriminalized federally (Celeste & Thompson-Dudiak, 2021).

Schedule II

These medications/drugs have the strictest regulations when compared to other prescription drugs because they are the most likely to be abused, diverted, or addicting. They include hydromorphone, meperidine, methadone, morphine, and oxycodone.

Morphine is used to treat soft tissue pain but also has been used to treat arthritis when other medications have failed.

Embeda® is a combination with naltrexone for the opioid-naïve patient, 20 mg/0.8 mg PO every 24 hours. Extended-release forms of morphine, such as MS Contin, should only be used for opioid-tolerant patients accustomed to ingesting over 400mg/day.

Morphine in selected forms should be used cautiously for patients with variable respiratory diseases such as COPD, obstructive asthma, hepatic or renal dysfunction, brain injury, increased intracranial pressure, or severe hypotension.

Hydromorphone (Dilaudid®) is a semisynthetic, phenanthrene opioid agonist. It is used for the treatment of persistent, severe pain that requires an extended treatment period with a daily opioid and for which alternative treatments are inadequate.

Fentanyl is supplied as a sublingual, transmucosal, nasal spray, transdermal patches, sublingual tablets, buccal lozenge, transmucosal lozenge, intramuscular injections, transmucosal tablets, intravenous injections, and electrically controlled transdermal patch. Different preparations of fentanyl are not interchangeable from microgram to microgram, even if administered via the same route. With the most popular clinic-level form, the transdermal 72-hour patch, providers should use a conversion table from other opiates used in the previous 24 hours to MMEs, then convert to fentanyl micrograms per hour.

Patients may use short-acting opioid agonists for the first 24 hours after stopping all other opiates at fentanyl patch initiation.

Hydrocodone/acetaminophen is a semisynthetic opiate agonist and a non-salicylate analgesic.

Opioid use requires an experienced clinician knowledgeable about the use of opioids, including the use of extended-release and long-acting opioids and how to mitigate the associated risks. All opiates have similar side effect profiles. From most to least severe, they cause all the obvious symptoms of CNS depression, such as decreased level of consciousness, increased respiratory depression, nausea, vomiting, constipation, slow gastric transit, and dry mouth. Unfortunately, hormonal and immunological dysfunction can happen with chronic use, physical dependence, tolerance, and rarely, hyperalgesia.

Schedule III

Schedule III drugs have a lower misuse and addiction potential than I and II. Medications in this category are often used for pain control or anesthesia. Drugs in this category may cause physical dependence but more commonly lead to psychological dependence. Examples of schedule III substances include ketamine, opioid analgesic products containing not more than 90 mg of codeine per dosage unit, and buprenorphine/naloxone oral film.

Schedule IV

These drugs are considered to have less likelihood of dependence and abuse. Carisoprodol is a centrally-acting skeletal muscle relaxant and salicylate analgesic. It is used for musculoskeletal conditions such as muscle spasms. Tramadol is an opiate sometimes used for patients experiencing intractable pain because of its impact on peripheral pain pathways, partial inhibition of serotonin reuptake, and low affinity for opioid receptors. Tramadol is thought to result in less sedation, respiratory depression, and potential for tolerance; however, constipation can still be problematic because of anticholinergic adverse effects.

Schedule V

Medications containing codeine must have less than 200 mg of codeine per 100 milliliters (mL), such as cough syrups, Tylenol® #3, and Tylenol® #4. Tylenol® #3 and Tylenol® #4 are an oral combination of analgesics, which include an opioid agonist. Codeine as an opiate has all the same side effects and adverse effects as other opioids; this medication may mistakenly be less protected from children, pets, or other adults because of the Tylenol® name. Tylenol® #3 and Tylenol® #4 are acetaminophen mixed with codeine.

Muscle relaxants

Tizanidine (Zanaflex®), a centrally acting muscle relaxant similar chemically to clonidine, works about as well as baclofen. Cyclobenzaprine (Flexeril®) is a muscle relaxant for acute musculoskeletal pain. Tizanidine causes dry mouth. It may cause orthostatic hypotension, especially in older adults.

Opioid agonists/antagonists 

Naloxone is an opioid antagonist, a derivative of oxymorphone employed for reversing the CNS and respiratory depression caused by opioid overdose. Auto-injectors and nasal formulations are available to treat or prevent an overdose outside of the healthcare setting. Naloxone nasal insufflation may be used in adults, children, and even infants at both the four and eight mg doses.

Medicaid, Medicare, and most insurance plans cover naloxone. There are free naloxone programs nationwide and prescription cards that can reduce the costs of prescribed naloxone to about $20.00 per kit. It should be remembered that as an opioid antagonist, it can precipitate a complete and sudden opioid withdrawal crisis for the patient. Too much naloxone can also remove all analgesic effects of the opioid being reversed; this can be extremely dangerous, even fatal, for an opioid-addicted infant and extremely uncomfortable for the opioid-addict in other age groups. Think severe instant withdrawal; a trip to the hospital to combat this may be necessary. The half-life of the nasal spray is comparable to the injection at about two hours. When given for fentanyl overdose, it may have to be repeated as fentanyl and other synthetic drugs, such as carfentanil, are 10,000 times stronger than morphine. Naloxone should be used cautiously with patients taking buprenorphine and cobicistat concurrently with protease inhibitors (Baker et al., 2010). As of this writing, naloxone has been made an over-the-counter medication by the FDA.

Buprenorphine is prescribed for patient support while tapering off opioid addiction and can be combined with naloxone to make a medication called Suboxone® (inSupport, 2023).

Methadone is structurally unrelated to morphine, and methadone is a Schedule II synthetic opiate agonist. Used in medically supervised opiate withdrawal and maintenance programs; also effective for relieving severe or chronic pain (Physicians' Desk Reference [PDR], n.d.a). For the treatment of opiate dependence, prescribers must register and comply with the Narcotic Addict Treatment Act (NATA) [21USC 823(g)].

Benzodiazepine antagonists

Flumazenil (Romazicon®) is not available commercially in an intranasal spray. Therefore, the overdosed patient must be transported immediately to the hospital for care. It treats benzodiazepine overdose, reverses benzodiazepine-induced sedation, and antagonizes the actions of zolpidem. It does not reverse the actions of barbiturates, opiate agonists, or tricyclic antidepressants (PDR, n.d.b).

Pain is assessed the same in every case. It is the details that matter here. Ask where it hurts and mark the pain map meticulously as a baseline. Document further using a pain assessment tool like the Provocation, Quality, Region (or Radiation), Severity (or Scale), and Timing (PQRST) model, Pain, Enjoyment of Life and General Activity (PEG) scale (attachment C), or 1-10 scale. The Wong-Baker scale has only five faces and is often used for children. The benefits of this scale are that it works regardless of the patient's age or language. Be sure to provide a patient-friendly professional interpreter and tools if the patient speaks a different language at home.

The following are website examples of a pain map, assessment tools, and scales.

• Pain Map
• PQRST Pain Assessment
• 1-10 pain scale
• Wong-Baker Scale

Get a complete social, family, and health history, including diseases or co-morbidities. Find out if they have seen other providers for this pain, what was tried, whether that helped, and if the pain changed. Knowledge is power. The more you know about this patient and the past, present, and future, the better you will help them and yourself.

Modified PEG tool 

If the pain is not specifically trauma-related, is it a product of diseases such as SCD, multiple sclerosis, or diabetes? Imaging studies are in order once you have eliminated obvious physiologic reasons for pain: injury, trauma, metabolic, or polypharmacy. Insurance companies require a certain order of imaging tests, or the patient must pay out of pocket. Usually, radiographs are followed by computed tomography (CT) scans, and finally, magnetic resonance imaging (MRIs) can be done. Insurance companies are poor decision-makers regarding what should be done and when. You will help your patient by preauthorizing tests. While different pains can all be assessed in about the same manner and treated differently, eventually, we can use pharmacogenetics as a more personalized prescription.

Healthcare providers and scientists have already discovered a deoxyribonucleic acid (DNA) option, which is useful to determine whether some drugs might be metabolized better by some people due to genetic expression and enzymes that either promote or inhibit metabolism. The cytochrome P450 (CYP 450) enzymes are responsible for many pharmaceutical metabolic actions, including opioids and other pain-alleviating drugs.

Many patients have a combination of types of pain. A severe injury or trauma patient might experience soft tissue and visceral and nerve pain. Bone fractures, burns, and crushing injuries are similarly complex to treat. Then, there are the most common patient complaints of disease-related pain, such as headaches, back pain, orthopedic sprains, and tears. Soft tissue pain is considered inflammatory pain that benefits from NSAIDs. For nerve pain, consider TCAs or antiseizure medication such as Neurontin. Are there labs or imaging needed to discern the cause of visceral pain? Treating the source of the pain is always the desirable answer if etiology can be identified. Consider over-the-counter anti-inflammatories such as Naprosyn or ibuprofen, non-anti-inflammatory acetaminophen, or a combination product.

Non-cancer disease pain like SCD is chronic with acute or chronic flares. The pain may require opioids such as MS Contin, with an immediate release "backup" such as oxycodone immediate release. For diseases and disorders such as arthritis, irritable bowel disease, ulcerative colitis, sciatica, migraines, fibromyalgia, and rheumatoid arthritis, to list a few, NSAIDs with nonpharmacological adjuncts are just as successful (Department of Defense, 2022). Cancer pain is often treated with long-acting or extended-release opioids.

The CDC (2022) and Goldstick et al. (2022) have made mention of the previous 2016 controlled substance guidelines being followed so strictly that patients were harmed by being tapered too quickly off opioid pain medications and not being given adequate support during the process (Dowell et al.,2022; Goldstick et al., 2022).

Tapering is the deliberate reduction of controlled substance dosage and lengthening intervals between doses. You can use tapering algorithms to help your patients stop taking these problematic medications. No perfect tapering algorithm fits every unique physical and psychological situation because every patient's mind, spirit, and body is unique. Research shows that out of almost 14,000 patients who tapered off opioids over one year, they continued to have pain, overdose, and increased mental health crisis issues, even suicide up to two years after the tapering started (Fenton et al., 2022). The VA has given provider advice for tapering: reducing opioid medications in the chronic opioid user taking more than 50 MMEs per day should not exceed 5-20% of the total daily dose per month (VA, 2019). The amount may help a patient to reduce or discontinue the opioid drug, keeping in mind that the patient must be educated that they cannot suddenly return to the original dose as they will no longer have the tolerance for it. It will precipitate an overdose (Fenton et al., 2022).

According to Fenton et al. (2022), 15.3% of patients in their meta-review successfully discontinued opioid use and had fewer mental health issues. According to the same study, however, the other 74% of the patients continued to need opioid pain medications at a reduced rate, and a few eventually increased the dosage they were taking (Fenton et al., 2022). This complex study led to several conclusions over and above these. The main gist of the study is that the dangers of opioids do not end with tapering the medications, and the patient should be followed and supported up to two years after initialization of the tapering efforts. The provider may need to consider keeping the pain goals fluid.

In today's medical practices, most providers lack consistent electronic calendar reminders and the time to achieve these needs. Providers must keep this at the forefront of their communications with the patient at every visit. Educating the patient regarding the need for extra follow-up, rotating medications, and starting nonpharmacological therapies early may help alleviate or reduce these mental health crises. Unfortunately, not all patients can be discontinued from pain medications and maintain a decent quality of life.

Per the CDC:

You can refer specifically to DSM-5 Criteria A and B for opioid withdrawal syndrome:

1. Either of the following:
   1. cessation of or reduction in opioid use that has been heavy and prolonged for several weeks or longer
   2. or administration of an opioid antagonist after a period of opioid use
2. Three or more of the following, developing within minutes to several days after criterion A: dysphoric mood; nausea or vomiting; muscle aches; lacrimation or rhinorrhea; pupillary dilation, piloerection, or sweating; diarrhea; yawning; fever; or insomnia.

Pain in hospice patients varies from patient to patient. Pain in this population is treated in ways that could not be employed for non-terminal disease pain. In the past, methadone, morphine, oxycodone, and fentanyl have all been used in nearly every formulation, from oral and sublingual tablets, capsules, lollipops, injections, automatic pumps, oral films, and transdermal patches. The medication dosages are titrated up to the level of effect, which will keep the dying patient from suffering from symptoms of uncontrolled pain while dying. The dosages are often extraordinarily high compared to a patient who is expected to live longer than six months.

In this situation, there is no need for limits concerning addiction or the need to taper the patient from the medications in the future. There is still the possibility of overdose as the metabolism slows at the end of life, and there is a need to be aware of that. Also, there is a possibility of drug diversion by family, visitors, and medical personnel (Cagle et al., 2020). Again, safe, locked storage of these medications should be in place, regardless of the inconvenience to the patient, providers, and caregivers. Pain medication in terminal cancers and other life-ending disease processes is multilayered and ever-changing due to the complexities of physiological changes.

Billing codes for this do exist. For Calendar Year (CY) 2023 Medicare Physician Fee Schedule Final Rule, go here.

Medicare is using the following pain management bundle codes effective January 01, 2023:

• The required initial face-to-face visit is at least 30 minutes provided by a physician or other qualified health professional; the first 30 minutes are personally provided by a physician or other qualified healthcare professional per calendar month.
• When using G3002, 30 minutes must be met or exceeded. In other words, the code includes assessment, diagnosis, and monitoring of the patient's pain, including working with other clinicians to manage treatment and lead to better outcomes. However, this code only describes the first 30 minutes of chronic pain management care.
• Providers who spend more than 30 minutes with the patient can report the new add-on code: G3003: Each additional 15 minutes of chronic pain management and treatment by a physician or other qualified healthcare professional per calendar month, listed separately in addition to code for G3002. When using G3003, 15 minutes must be met or exceeded. Because G3003 is considered an add-on code, providers can only report it if they spend more than 30 minutes on chronic pain management (Kim, 2023).

Billing codes and evaluation and management (E&M) codes are ever-changing. For a complete sheet, go here. For the complete document with accompanying grids and in-depth instructions, go here.

Opioid use, addiction, and diversion are frequently occurring issues in healthcare that we all must be aware of. It is pertinent to assess and manage pain while educating patients on the precautions and risk factors of opioid use and pain management. Pain is a subjective experience, and we must manage pain in the safest manner possible.

• American Psychiatric Association (APA). (2022). Diagnostic and statistical manual of mental disorders, text revision. (DSM-5-TR). (5th ed., text rev.). Visit Source.
• Anderson, D. M., & Rees, D. I. (2023). The public health effects of legalizing marijuana. Journal of Economic Literature, 61(1), 86-143. Visit Source.
• Baker, J., Rainey, P. M., Moody, D. E., Morse, G. D., Ma, Q., & McCance-Katz, E. F. (2010). Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir. The American journal on addictions, 19(1), 17–29. Visit Source.
• Boring, B. L., Ng, B. W., Nanavaty, N., & Mathur, V. A. (2022). Over-rating pain is overrated: A fundamental self-other bias in pain reporting behavior. The Journal of Pain, 23(10), 1779–1789. Visit Source.
• Cagle, J. G., McPherson, M. L., Frey, J. J., Sacco, P., Ware, O. D., Wiegand, D. L., & Guralnik, J. M. (2020). Estimates of medication diversion in hospice. JAMA, 323(6), 566-568. Visit Source.
• Celeste, M. A., & Thompson-Dudiak, M. (2021). Has the marijuana classification under the Controlled Substances Act outlived its definition? Connecticut Public Interest Law Journal, 20(1), 18-59. Visit Source.
• Centers for Disease Control and Prevention (CDC). (2021) Prescription drug monitoring programs. Centers for Disease Control and Prevention. Visit Source.
• Centers for Disease Control and Prevention (CDC). (2022). Guideline recommendations and guiding principles. Centers for Disease Control and Prevention. Visit Source.
• Champagne-Langabeer, T., Cardenas-Turanzas, M., Ugalde, I. T., Bakos-Block, C., Stotts, A. L., Cleveland, L., Shoptaw, S., & Langabeer, J. R. (2022). The impact of pediatric opioid-related visits on U.S. Emergency Departments. Children, 9(4), 524. Visit Source.
• Department of Defense. (2022). VA/DoD clinical practice guideline for the use of opioids in the management of chronic pain. Department of Veterans Affairs. Visit Source.
• Dowell, D., Ragan, K. R., Jones, C. M., Baldwin, G. T., & Chou, R. (2022). CDC clinical practice guideline for prescribing opioids for pain- United States, 2022. Morbidity and Mortality Weekly Report (MMWR), 71(3), 1–95. Visit Source.
• Fenton, J. J., Magnan, E., Tseregounis, I. E., Xing, G., Agnoli, A. L., & Tancredi, D. J. (2022). Long-term risk of overdose or mental health crisis after opioid dose tapering. JAMA Network Open, 5(6), e2216726. Visit Source.
• Ferreira, G. E., Abdel-Shaheed, C., Underwood, M., Finnerup, N. B., Day, R. O., McLachlan, A., Eldabe, S., Zadro, J. R., & Maher, C. G. (2023). Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ (Clinical research ed.), 380, e072415. Visit Source.
• Food and Drug Administration (FDA). (2009). DURAGESIC® CII: (Fentanyl Transdermal System). Food and Drug Administration. Visit Source.
• Gill, B., Obayashi, K., Soto, V. B., Schatman, M. E., & Abd-Elsayed, A. (2022). Pill counting as an intervention to enhance compliance and reduce adverse outcomes with analgesics prescribed for chronic pain conditions: A systematic review. Current Pain and Headache Reports, 26, 883–887. Visit Source.
• Goldstick, J. E., Guy, G. P., Losby, J. L., Baldwin, G. T., Myers, M. G., & Bohnert, A. S. (2022). Patterns in nonopioid pain medication prescribing after the release of the 2016 guideline for prescribing opioids for chronic pain. JAMA Network Open, 5(6), e2216475. Visit Source.
• Hartney, E. B. S. (2023). DSM 5 Criteria for Substance Use Disorders. Verywell Mind. Visit Source.
• HealthyWomen Editors. (2020). Bias, chronic pain and access to care. HealthyWomen. Visit Source.
• Iowa Administrative Code (IAC). (2019). Chapter 7: Advanced registered nurse practitioners. Iowa Administrative Code, 655(7.1), 1-5. Visit Source.
• inSupport. (2023) Suboxone Copay Assistance Program. inSupport. Visit Source.
• Kalkman, G. A., Van den Brink, W., Pierce, M, Atsmac, F., Visser, K. C. P., Schers, H. J., van Dongen, R. T. M., Kramers, C., & Schellekens, A. F. A. (2022). Monitoring opioids in Europe: the need for shared definitions and measuring drivers of opioid use and related harms. European Addiction Research, 28(3), 231–240. Visit Source.
• Keister, L. A., Stecher, C., Aronson, B., McConnell, W., Hustedt, J., & Moody, J. W. (2021). Provider Bias in prescribing opioid analgesics: a study of electronic medical Records at a Hospital Emergency Department. BMC public health, 21(1), 1518. Visit Source.
• Kim, T. (2023). CMS pain management codes for 2023. MedCentral, 23(2). Visit Source.
• Manchikanti, L., Singh, V. M., Staats, P. S., Trescot, A. M., Prunskis, J., Knezevic, N. N., Soin, A., Kaye, A. D., Atluri, S., Boswell, M. V., Abd-Elsayed, A., & Hirsch, J. A. (2022). Fourth Wave of Opioid (Illicit Drug) Overdose Deaths and Diminishing Access to Prescription Opioids and Interventional Techniques: Cause and Effect. Pain physician, 25(2), 97–124. Visit Source.
• Marr, C., Schmitgal, D., & Parsh, B. (2022). Addressing healthcare bias in caring for patients with sickle cell disease. Nursing, 52(3), 10–11. Visit Source.
• Merriam-Webster. (n.d.). Iatrogenic. In Merriam-Webster.com dictionary. Visit Source.
• Mullins, S., Hosseini, F., Gibson, W., & Thake, M. (2022). Physiological changes from ageing regarding pain perception and its impact on pain management for older adults. Clinical medicine (London, England), 22(4), 307–310. Visit Source.
• National Institute on Drug Abuse (NIDA). (2022). Naloxone DrugFacts. National Institute on Drug Abuse. Visit Source.
• National Institute on Drug Abuse (NIDA). (2023). Drugs, Brains, and Behavior: The Science of Addiction. National Institute on Drug Abuse. Visit Source.
• Niculescu, A. B., Le-Niculescu, H., Levey, D. F., Roseberry, K., Soe, K. C., Rogers, J., Khan, F., Jones, T., Judd, S., McCormick, M. A., Wessel, A. R., Williams, A., Kurian, S. M., & White, F. A. (2019) Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs. Molecular Psychiatry, 24, 501–522. Visit Source.
• Preuss, C. V., Kalava, A., & King, K. C. (2023). Prescription of Controlled Substances: Benefits and Risks. In StatPearls. StatPearls Publishing. Visit Source.
• Queremel Milani, D. A., & Davis, D. D. (2023). Pain Management Medications. In StatPearls. StatPearls Publishing. Visit Source.
• Physicians’ Desk Reference [PDR]. (n.d.a). Dolophine. Visit Source. PDR. Visit Source.
• Physicians’ Desk Reference [PDR]. (n.d.b). Romazicon. PDR. Visit Source.
• Raja, S. N., Carr, D. B., Cohen, M., Finnerup, N. B., Flor, H., Gibson, S., Keefe, F. J., Mogil, J. S., Ringkamp, M., Sluka, K. A., Song, X. J., Stevens, B., Sullivan, M. D., Tutelman, P. R., Ushida, T., & Vader, K. (2020). The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain, 161(9), 1976–1982. Visit Source.
• Salvatore, P. P., Guy, G. P., & Mikosz, C. A., Jr. (2022). Changes in opioid dispensing by medical specialties after the release of the 2016 CDC guideline for prescribing opioids for chronic pain. Pain Medicine, 23(11), 1908–1914. Visit Source.
• Shaw, G. (2022). Surveillance software spots elusive signs of drug diversion. Pharmacy Practice News. Visit Source.
• Substance Abuse and Mental Health Services Administration (SAMHSA). (2022). 2021 National survey of drug use and health (NSDUH) releases. Substance Abuse and Mental Health Services Administration. Visit Source.
• U.S. Department of Veterans Affairs (VA). (2016). Pain management opioid taper decision tool, A VA clinician's guide. U.S. Department of Veterans Affairs. Visit Source.
• Wei-Hsuan, L. C., Donohue, J. M., Yang, Q., Huang, J. L., Chang, C. Y., Weiss, J. C., Guo, J., Zhang, H. H., Cochran, G., Gordon, A. J., Malone, D. C., Kwoh, C. K., Wilson, D. L., Kuza, C. C., & Gellad, W. F. (2022). Developing and validating a machine-learning algorithm to predict opioid overdose in Medicaid beneficiaries in two US states: A prognostic modelling study. The Lancet-Digital, 4(6), E455-E465. Visit Source.