Continuing Education Activity

One of the most difficult challenges for any prescriber is distinguishing between the legitimate prescription of controlled substances versus the prescription potentially used for illegitimate purposes. To discern the difference, prescribers need to recognize the signs, symptoms, and treatment of acute and chronic pain and the signs and symptoms of patients misusing controlled substances. This activity assists interprofessional team members by helping develop an awareness of appropriate dosing and substance control and recognizing patients that may be abusing these drugs for non-legitimate purposes.

Objectives:

• Describe the Controlled Substances Act and its legal application to the prescribing and dispensing of medications.

• Explain the characteristics of addictive disorders.

• Identify the causes and types of pain.

• Outline the role of the interprofessional team in assessing and treating pain appropriately and managing the use of controlled substances.

Introduction

One of the most difficult challenges for any prescriber is distinguishing between the legitimate prescription of controlled substances versus the prescription potentially used for illegitimate purposes. To discern the difference, prescribers need to understand the signs, symptoms, and treatment of acute and chronic pain and the signs and symptoms of patients misusing controlled substances.[1][2]

A common reason people seek the care of medical professionals is pain relief. While many categories of pain medications are available, opioid analgesics are FDA-approved for moderate to severe pain. As such, they are a common choice for patients with acute, cancer-related, neurologic, and end-of-life pain. Prescribing opioid analgesics for chronic pain is controversial and fraught with inconclusive standards.

In the 1990s, due to the chronic failure of health professionals to undertreat severe pain, opioid analgesic prescribing was expanded. Unfortunately, this led to increased overuse, diversion of drugs, opioid use disorder, and overdose. The "Catch-22" seems to be either health professionals undertreat, and there is needless suffering, or they overtreat, with a potential to cause adverse effects like increased opioid analgesic use disorder and potential overdose.

The prescribing of opioid analgesics peaked in 2011. Since then, both prescribing and overdose have been declining, yet as a society, in both the lay and scientific literature, there are grave concerns that we are still in the middle of an opioid crisis.[3]

Perhaps the biggest challenge of caring for patients with pain is that individuals have different tolerance levels and require variable opioid doses to obtain adequate pain relief. Patients may have a range of behavioral, cultural, emotional, and psychologic responses to pain versus a substance use disorder; often, it is challenging to tell the difference. All health professionals engaged in pain management need an understanding of the treatment recommendations and safety concerns in prescribing opioid analgesics. Appropriate opioid prescribing requires a thorough patient assessment, short and long-term treatment planning, close follow-up, and continued monitoring. All providers need to be aware of appropriate patient assessment and treatment planning, and the possibility of use disorder, diversion, and potentially dangerous behavioral responses to controlled substances, e.g., opioid analgesics differ from pseudoaddiction and physical dependence.

It is unfortunately clear that many clinicians know little about opioid use disorder. They do not understand it is a disease, and many believe opioid dependence is the same as opioid use disorder. Lack of a clear understanding results in clinicians confusing a patient with chronic non-use disorder with the one misusing their prescribed opioid. Lack of training and educational deficits often interfere with the appropriate prescription of opioid analgesic agents. To prevent the misuse of controlled substances, providers that prescribe controlled substances should learn prescribing practices that minimize or prevent adverse consequences.[4]

Definitions

• Addiction - according to the American Society of Addiction Medicine (ASAM): "Addiction is a primary, chronic disease of brain reward, motivation, memory, and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social, and spiritual manifestations. This is reflected in an individual pathologically pursuing reward or relief by substance use and other behaviors." Addiction is now termed "use disorder," and is characterized by an inability to consistently abstain, craving the drug, impairment in behavioral control, diminished ability to recognize significant problems with one's behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, use disorder often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, use disorder is progressive and can result in disability or premature death." [5] 

• Appropriate opioid analgesic prescribing: This involves providing pain control while minimizing toxicity, use disorder, or the risk of use disorder and implementing safeguards to reduce drug diversion.

• Inappropriate opioid analgesic prescribing: non-prescribing, inadequate prescribing, excessive prescribing, or continued prescribing despite evidence of the lack of effective opioid analgesic treatment.

• Controlled substances: These are drugs or medications that possess the potential for being misused and are considered to be substances that have a substantially high risk of resulting in substance use disorder.

• Opioid analgesics: these are drugs that dull the senses and relieve pain, e.g., morphine. Also, these medications may induce sleep. Please note that the Drug Enforcement Administration (DEA, USA) uses the term "narcotic" to refer to drugs that are opioid analgesics.

Five Characteristics of Addiction/Use Disorder (ASAM)

1. Craving for drug or reward
2. Diminished recognition of significant problems in one's behavior
3. Dysfunctional emotional response
4. Impairment in behavioral control
5. Inability to consistently abstain 

Drug Schedules of Controlled Substances

All providers should be familiar with the guidelines and laws for each schedule, which have, as their basis, the purpose of the drug and the risk of use disorder. In the United States, controlled substances are under strict regulation by both federal and state laws that guide their manufacture and distribution. Controlled substances have a high risk of resulting in addiction and substance use disorder. As the schedules decrease, I-V, the drugs listed within each category have a lower potential to cause a substance use or addiction disorder. 

Controlled Substance Act

In the United States, the Comprehensive Drug Abuse Prevention and Control Act was passed in 1970, and it included the Controlled Substance Act. The Controlled Substance Act covers drug:

• Classification and regulation, according to their content and purpose.
• Manufacturing
• Distribution
• Exportation and sale

The Controlled Substance Act established five drug schedules and classified them to control their manufacture and distribution. Part of the regulation requires providers prescribing scheduled drugs and pharmacists filling them to obtain a license from the Drug Enforcement Administration. Health professionals' licenses include specific license numbers allowing controlled substance prescriptions to be tracked and linked to a particular provider or distributor.

Each of the five schedules has parameters based on their medical value, the risk of addiction, and the ability to cause harm. The schedules range from Schedule I (most potential for addiction/use disorder) to Schedule V (least potential for addiction/use disorder).

Schedule I

• Schedule I drugs possess the highest potential for use disorder and misuse. They have no medical use and are illicit or "street" drugs.
• Examples of Schedule I drugs include heroin, lysergic acid diethylamide, mescaline, methylenedioxymethamphetamine (MDMA), and methaqualone.
• Marijuana, which is legal in some states, is still classified as a Schedule I drug at the federal level as of this writing.

Schedule II

• Schedule II drugs have a reduced potential for use disorders than Schedule I. They are at high risk for both physical and psychological dependence. They have a high capacity for both use disorder and misuse. They are typically prescribed to treat severe pain, anxiety, insomnia, and ADHD.
• Examples of Schedule II substances include fentanyl, hydromorphone, meperidine, methadone, morphine, oxycodone, fentanyl, dextroamphetamine, methylphenidate, methamphetamine, pentobarbital, and secobarbital.
• They previously had to be prescribed only via paper prescription but now are permitted to be electronically transmitted. (Electronic Prescribing of Controlled Substances or EPCS).
• No refills are allowed. 
• Schedule II drugs have the tightest regulations when compared to other prescription drugs.

Schedule III

• Schedule III drugs have a lower misuse potential than I and II. Drugs in this category may cause physical dependence but more commonly lead to psychological dependence. Medications in this category are often used for pain control, or anesthesia, or appetite suppression.
• Examples of Schedule III substances include benzphetamine, ketamine, phendimetrazine, and anabolic steroids.
• Opioid analgesics in this schedule include products containing not more than 90 milligrams of codeine per dosage unit and buprenorphine.
• Schedule III drugs are prescribable verbally over the phone, with a paper prescription, or via EPCS.
• Within a six-month time frame, refill requirements are such that the drug can only have five refills. 

Schedule IV

• Schedule IV drugs have an even lower misuse potential than I, II, or III. They have a limited risk of physical or psychological dependence.
• Examples of Schedule IV substances include: alprazolam, carisoprodol, clonazepam, clorazepate, diazepam, lorazepam, midazolam, temazepam, tramadol, and triazolam.
• Drugs in this class may be utilized for pain control as long as the provider deems the drug medically necessary and the patient would benefit.
• Schedule IV drugs are prescribable verbally over the phone, with a paper prescription, or via EPCS.
• Refills are permitted up to five times in a six-month timeframe from the issuance date.

Schedule V

• Schedule V drugs are the least likely of the controlled substances to be misused. They result in very limited physical or psychological dependence.
• Examples include cough medicines with codeine, antidiarrheal medications that contain atropine/diphenoxylate, pregabalin, and ezogabine.
• Despite their low abuse potential, they still need to be managed appropriately and administered with care.
• When they contain codeine, it must have less than 200 mg of codeine per 100 mL.
• Partial prescription fills cannot occur more than six months after the issue date. When a partial fill occurs, it is treated in the same manner and with the same rules as a refill of the drug.

Drug Use Disorder, Abuse, and Misuse

The use disorder of a drug differs from abuse and misuse of a drug.

The drugs taken may be illicit street or stolen drugs or obtained via a legal prescription. Misusing a drug usually involves taking the drug in a harmful or detrimental way, resulting in personal, professional, or social problems. A patient abusing an opioid analgesic may no longer be appropriately interacting with their family or friends or be able to perform their duties at work.

Misuse of a controlled substance refers to using a prescribed drug in a way that was not intended. It may be deliberate or accidental. A negative result may or may not occur. Examples of misuse include taking too much of a drug, using an incorrect dose, an incorrect route, or using prescription drugs written for another person.

Controlled substances include both prescription drugs and illicit drugs with no recognized medical value. Both have the potential to be abused or misused. While Schedule I drug use is illegal, prescription drugs found in Schedules II-V are also commonly abused and misused, and their misuse is a challenging problem that has increased over the last several years.

The Centers for Disease Control and Prevention has declared prescription drug abuse a problem of epidemic proportions. The CDC believes that absent checks and balances on the prescription and distribution of controlled substances, including those prescribed for medical use, have the potential for abuse and that misuse will continue to increase.

Prescriber Shopping

Unfortunately, a common practice among those that deliberately misuse controlled substances is to seek out multiple sources of drugs. They do this by seeing different health care providers and presenting with a list of complaints that are often fictitious and different for each provider. The patient may be able to obtain multiple prescriptions and then fill them at different pharmacies. Many states have enacted systems that allow providers to see all of the prescriptions written for each patient. The use of these systems is gradually curbing "prescriber shopping."[6]

Diversion

Some prescription drugs will sell on the street for as much as $50 a tablet. Diversion is when a patient sells their drugs as a method of earning money. Drugs may also be sold to buy food, pay expenses, or purchase more potent street drugs. Worse, in some cases, healthcare providers may divert drugs from patients for the providers' personal use or sell them to someone else.

Some individuals use controlled substances in ways for which they were not originally intended. Rather than pain control, they may be used to stay awake, induce sleep, or get "high." Before the popularity of prescription drug diversion, the only method to obtain illicit drugs was to import from other countries or manufacture them in private labs. Today, law enforcement agencies have the tremendous challenge of dealing with prescription drugs sold by diversion and illicit drugs imported or manufactured. In both instances, these drug sales and usage result in increased criminal activity, dangerous overdoses, and death. 

Methods of Obtaining Prescription Drugs

A review of multiple studies demonstrates a variety of ways individuals obtain prescription drugs. The following summarizes the studies' findings.

• 55% free from a friend or relative
• 20% from a prescriber
• 10% purchased from a friend or relative
• 5% stolen from a friend or relative
• 5% purchased from a drug dealer
• 2% from multiple doctors
• 1% from theft from medical practice or pharmacy
• Less than 1% obtain them from the internet

Studies also reveal the source of the majority of these drugs was a single legal prescriber.

Provider Opioid Knowledge Deficit 

There are substantial knowledge gaps around appropriate and inappropriate opioid analgesic prescribing, including deficits in understanding current research, legislation, and appropriate prescribing practices. Providers often have knowledge deficits that include:

• Understanding of addiction
• At-risk opioid addiction populations
• Prescription vs. non-prescription opioid addiction
• The belief that addiction and dependence on opioids are synonymous
• The belief that opioid addiction is a psychological problem instead related to a chronic painful disease

With a long history of misunderstanding, poor society, provider education, and inconsistent laws, prescribing opioids has resulted in significant societal challenges that will only resolve with significant education and training.

Misuse of Controlled Substances

Unfortunately, the misuse of controlled substances resulting in morbidity and mortality is rampant.[7] According to the National Survey on Drug Use and Health, 2016, performed by the US Department of Health and Human Services, over 10 million people misuse prescription pain medications, and over 2 million misuse sedatives, stimulants, and tranquilizers each year. The same study found that the most common reason for misuse is for treating physical pain. The Center for Disease Control estimates more than 40,000 people die each year die from an opioid overdose. 

Controlled Substances

Three common classes of controlled substances are commonly misused: opioids, depressants, and stimulants. 

Opioids

Opioids are prescribed for pain control by binding to mu-opioid receptors in the central nervous system reducing pain signals to the brain as well as receptors in the GI tract and respiratory system, and are used to treat pain, diarrhea, and cough.[8]

Common Opioids

Codeine - One of the most commonly taken opioid medications. It is at the center of the opioid addiction problem in the United States and thus is highly regulated. Its main indications are pain and cough.

FDA-Approved Indication

Pain

Codeine plays a role in the treatment of mild to moderate pain. Its use is recognized in chronic pain due to ongoing cancer and palliative care. However, the use of codeine to treat other types of chronic pain remains controversial. Chronic pain, defined by the International Association for the Study of Pain, is pain persisting beyond the standard tissue healing time, which is three months.[1] The most prevalent causes of non-cancer chronic pain include back pain, fibromyalgia, osteoarthritis, and headache.

Non-FDA Approved Indications

Cough

Codeine is useful in the treatment of various etiologies producing chronic cough. Also, 46% of patients with chronic cough do not have a distinct etiology despite a proper diagnostic evaluation. Codeine produces a decrease in cough frequency and severity in these patients. However, there is limited literature demonstrating the efficacy of codeine in chronic cough. The dose can vary from 15 mg to 120 mg a day. It is, however, indicated in the management of prolonged cough (in specific populations like lung cancer) usually as 30 mg every 4 to 6 hours as needed.

Restless Leg Syndrome

Codeine is effective in treating restless leg syndrome when given at night time, especially for those whose symptoms are not relieved by other medications.

Persistent Diarrhea (Palliative)

Codeine and loperamide are equally effective, and the choice between them has its basis in the assessment of the physician evaluating the small but undoubted addictive potential of codeine versus the higher cost of loperamide and an individual difference in patient's vulnerability to adverse effects.

Fentanyl - Transdermal patch and IV, commonly abused and used in mixture with other drugs. Fentanyl is a synthetic opioid that is 80 to 100 times stronger than morphine and is often added to heroin to increase its potency. It can cause severe respiratory depression and death, particularly when mixed with other drugs or alcohol. It has high addiction potential.[9]

Hydrocodone - Hydrocodone is a schedule II semi-synthetic opioid medication used to treat pain. Immediate-release (IR) hydrocodone is available as a combination product (combined with acetaminophen, ibuprofen, etc.) and is FDA approved for the management of pain severe enough to require an opioid analgesic and for which alternative (non-opioid) treatments are inadequate. Single-entity hydrocodone is only available in extended-release (ER) formulations. It is FDA approved to treat persistent pain severe enough to require 24-hour, long-term opioid treatment, for which alternative treatments are inadequate. Hydrocodone is also an antitussive and is indicated for cough in adults.[10]

Morphine Sulfate - FDA-approved usage of morphine sulfate includes moderate to severe pain that may be acute or chronic. Most commonly used in pain management, morphine provides significant relief to patients afflicted with pain. Clinical situations that significantly benefit from medicating with morphine include managing palliative/end-of-life care, active cancer treatment, and vaso-occlusive pain during sickle cell crises. Morphine is widely used off-label for almost any condition that causes pain. In the emergency department, morphine is given for musculoskeletal pain, abdominal pain, chest pain, arthritis, and even headaches when patients fail to respond to first and second-line agents. Morphine is rarely used for procedural sedation. However, clinicians will sometimes combine a low dose of morphine with a low dose of benzodiazepine-like lorazepam for minor procedures.[11]

Oxycodone - An opioid agonist prescription medication. The oxycodone immediate-release formulation is FDA-approved for managing acute or chronic moderate to severe pain for which other treatments do not suffice, and for which opioid medication is appropriate. The extended-release formulation is FDA-approved for the management of pain severe enough to require continuous (24 hours per day), long-term opioid treatment, and for which there are no alternative options to treat the pain. The oxycodone to morphine dose equivalent ratio is approximately 1 to 1.5 for immediate-release and 1 to 2 for extended-release formulations.[12]

Tramadol - Tramadol is an FDA-approved medication for pain relief. It has specific indications for moderate to severe pain. It is considered a class IV drug by the FDA. Due to possible abuse and addiction potential, limitations to its use should be for pain that is refractive to other pain medication, such as non-opioid pain medication. There are two forms of tramadol: extended-release and immediate release. The immediate release is not for use as an "as needed" medication; instead, it is for pain of less than a week duration. For pain lasting more than a week, extended-release is the therapeutic choice — the indication for extended-release is for pain control under 24-hour management or an extended period.

Off-label, the drug is useful for premature ejaculation and restless leg syndrome refractory to other medications. For the off-label use of tramadol for premature ejaculation, both sporadic and daily use is effective for treating the condition. Patients indicate a preference for "as needed" therapy for premature ejaculation due to the lack of side effects compared to the daily use of tramadol.[13]

Addiction, Dependence, and Tolerance

While each of these terms is similar, providers should be aware of the differences.

• Addiction - the constant need for a drug despite harmful consequences.
• Pseudoaddiction - constant fear of being in pain, hypervigilance; usually, there is a resolution with pain resolution.
• Dependence - physical adaptation to a medication where it is necessary for normal function and withdrawal occurs with lack of the medication.
• Tolerance - lack of expected response to a medication increasing dose to achieve the same pain relief resulting from CNS adaptation to the medication over time.

Mainstreaming Addiction Treatment (MAT) Act

The Mainstreaming Addiction Treatment (MAT) Act provision updates federal guidelines to expand the availability of evidence-based treatment to address the opioid epidemic. The MAT Act empowers all health care providers with a standard controlled substance license to prescribe buprenorphine for opioid use disorder (OUD), just as they prescribe other essential medications. The MAT Act is intended to help destigmatize a standard of care for OUD and will integrate substance use disorder treatment across healthcare settings. 

As of December 2022, the MAT Act has eliminated the DATA-Waiver (X-Waiver) program. All DEA-registered practitioners with Schedule III authority may now prescribe buprenorphine for OUD in their practice if permitted by applicable state law, and SAMHSA encourages them to do so. Prescribers who were registered as DATA-Waiver prescribers will receive a new DEA registration certificate reflecting this change; no action is needed on the part of registrants.

There are no longer any limits on the number of patients with OUD that a practitioner may treat with buprenorphine. Separate tracking of patients treated with buprenorphine or prescriptions written is no longer required. 

Pharmacy staff can now fill buprenorphine prescriptions using the prescribing authority's DEA number and does not need a DATA 2000 waiver from the prescriber. However, depending on the pharmacy, the dispensing software may still require the X-Waiver information in order to proceed. Practitioners are still required to comply with any applicable state limits regarding the treatment of patients with OUD.  Contact information for State Opioid Treatment Authorities can be found here: https://www.samhsa.gov/medicationassisted-treatment/sota. 

Etiology

The pain associated with acute injuries may require scheduled drug treatment. For some patients, the acute pain experienced may become chronic. Pain can be the result of neurologic and musculoskeletal conditions. Pain may also be local or systemic as a complication of diseases.[14] Chronic pain syndromes have associations with many long-term conditions and diseases.

Common Causes of Legitimate Pain

Neurologic and Systemic Diseases that Cause Pain

• Alcohol use disorder
• Ankylosing spondylitis
• Brachial plexus traction injury
• Cancer
• Complex regional pain syndrome
• Diabetic polyneuropathy
• Drugs
• Fibromyalgia
• Giant cell arteritis
• Glaucoma
• Infections
• Migraine
• Osteoarthritis
• Osteomalacia
• Pernicious anemia
• Polymyalgia rheumatica
• Polyneuropathies
• Polyradiculopathies
• Postherpetic neuralgia
• Rheumatoid arthritis
• Side effects of chemotherapy or radiation therapy
• Sjögren syndrome
• Spinal stenosis
• Systemic lupus erythematosus (SLE)
• Smoking
• Temporomandibular joint dysfunction
• Thoracic outlet syndrome
• Trigeminal neuralgia
• Thyroid disease

Psychological Causes of Pain

• Anxiety
• Depression
• Emotional disorders
• Personality disorders
• Sleep disorders

Musculoskeletal Causes of Pain

• Ankylosing spondylitis
• Chronic overuse
• Dislocations
• Fractures
• Muscular strains
• Myofascial diseases
• Polymyalgia rheumatica
• Polymyositis
• Osteomyelitis
• Osteoarthritis
• Osteoporosis
• Rheumatoid arthritis
• Mechanical back injury

Common Causes of Situations Resulting in Illegitimate Use of Controlled Substances

Any of the above conditions and causes of acute pain may progress to chronic pain. When there is chronic use of pain medicine, the risk of developing a use disorder to a controlled substance to control the pain increases. Risk factors for a use disorder with a pain medication include:

• Age
• Life circumstances
• Medical problems
• Physical problems

Factors that increase the risk of developing use disorder include:

• If an individual uses drugs to stay awake or sleep, they are at increased risk of developing a use disorder.
• If an individual undergoes exposure to other individuals with use disorder, they are at a higher risk of developing use disorder.
• If a parent has a use disorder, there is a greater chance the children will develop a use disorder.
• Individuals who engage in prescriber shopping are at increased risk of use disorder.
• If an individual receives multiple drugs from multiple prescribers, they are at a higher risk of addiction.

Factors that decrease the risk of use disorder include:

• Middle-age
• No psychiatric history
• Relaxed personality
• Those that follow instructions

Epidemiology

Acute and chronic pain is a significant problem in the United States and worldwide. In the United States alone, it affects more than 100 million Americans annually. The cost of evaluating and treating pain is substantial, estimated to be over 600 billion dollars annually, including those unable to work as a direct consequence of pain syndromes.

Pain Frequency

Pain is among the primary reasons individuals receive federal and private disability payment support.

• Pain syndromes affect as much as 50% of the United States population at some point in their lifetime.
• For those over 21 years of age, approximately 10% have experienced pain for 3 to 12 months, and almost 50% have had pain longer than one year. Nearly half report their pain is uncontrolled.
• Over 5 million Americans are receiving long-term opioid analgesics for chronic pain. For many of those, the pain is disabling.

The frequency of Acute and Chronic Pain is Believed to be Increasing for Several Reasons

• The increased average age of the population
• Increased diversion of pain medications due to state and federal enforcement of illicit drugs
• Increased frequency of surgery and post-operative pain management with opioid analgesics
• Increased obesity with comorbid problems such as muscle strain and joint deterioration
• Increased treatment of pain
• The survival of military and civilians with traumatic conditions has increased with increased numbers in pain during recovery

Frequency of Opioid-Related Concerns

The Frequency of Opioid Prescribing and Consumption

• Even though the lay literature reports that opioid prescribing is on the rise, opioid analgesic prescribing is actually declining.
• Hydrocodone, methadone and fentanyl prescribing has decreased by as much as one-third since peaking in 2011.
• Before 1990, physicians rarely prescribed opioids for noncancer pain. Starting in the 1990s, physicians were encouraged to control pain as this was the "fifth vital sign." The use of opioid analgesic pain medicine increased substantially. The consensus is that overprescribing of opioid analgesics occurs, but it is still unclear in the literature where this occurs and the exact circumstances when prescriptions are inappropriate.
• There has been a drastic reduction in opioid analgesic prescribing and overdose, but it has also resulted in sometimes making it difficult for patients with legitimate pain to receive pain relief.
• Abuse in the healthcare system has resulted in increasing barriers to access; for some, increasing difficulty finding health professionals willing or able to prescribe pain medication.
• Opioid analgesic prescribing has also declined in Florida.
• Worldwide, the consumption of opioid analgesics has substantially increased over the last 20 years. 

Opioid Overdose

• Nationally, opioid-related overdose fatalities are decreasing, peaking in 2011 and dropping since.
• In Florida, fatalities from illicit drugs have increased, whereas there has been a decrease in prescription overdose fatalities.
• Opioid analgesic fatalities often occur with co-ingestion of benzodiazepines, e.g., diazepam. 

Controlled Substance Use And Addiction/Use Disorder

The use disorder of prescription drugs has become a common problem. Those afflicted may not fit the profile of an individual addicted to street drugs. They are often individuals with jobs and chronic pain syndromes. For multiple reasons, they may have sought self-medication to control the pain while maintaining their lifestyles. As societal views normalize using prescription drugs, access may be easier and safer than obtaining illicit drugs. Since medications may be covered under insurance, more and more people choose to figure out ways to obtain prescription drugs over the use of illicit drugs.

Prescription drug use disorder is more common in some demographic populations than others. It is a more common problem with:

• Individuals that use opioids inappropriately
• Those who regularly use opioids
• Those that use alcohol or tobacco
• Women who tend to abuse sedatives and tranquilizers

Illicit drug use is growing. In the United States, since the restrictions on prescription drug use, heroin use has increased dramatically. Heroin used to be a rare problem, but as drug enforcement agencies clamped down on prescription abuse, those addicted turned to Schedule I drugs such as heroin. Individuals may also move from abusing Schedule II prescription drugs to abusing Schedule I illicit drugs. Those with use disorder tend to follow the path of least resistance. If unable to easily obtain prescription drugs, they turn to illicit drugs or vice versa.

Often, patients are not appropriately educated on the addictive potential of controlled substances such as benzodiazepines or opioids. They are not aware of the danger when prescription renewals are easily accessible, especially if they see more than one prescriber.

Of those patients receiving treatment in an emergency department, some are actually seeking additional medication to supplement their current consumption of opioids. Studies have found that of patients prescribed opioids in an emergency setting, 5% to 10% are already consuming opioid medications from other prescribers. Many states have made this problem less prevalent by instituting statewide reporting of controlled substance prescriptions.

Pathophysiology

Pain is a common reason patients seek medical care. Pain occurs due to both emotional and sensory inputs and has acute or chronic components. Acute pain has associations with the sympathetic nervous system with physical findings that include an elevated heart rate, respiratory rate, and blood pressure. Pupillary dilation and diaphoresis may be evident.

Chronic pain usually does not involve the sympathetic nervous system and may be associated with depression, fatigue, loss of appetite, and loss of libido.

Acute Pain

It typically occurs in response to acute tissue injury and results from activation of peripheral pain receptors and specific A-delta and C sensory nerve fibers (nociceptors).

Chronic Pain

It typically occurs in response to ongoing tissue injury and is thought to be caused by persistent activation of A-delta and C sensory fibers. The severity of tissue injury does not generally predict the severity of the pain. Chronic pain may result from damage or dysfunction of the peripheral or central nervous system causing neuropathic pain.

Nociceptive Pain

Nociceptive pain can be somatic or visceral. 

Somatic pain receptor stimulation produces dull or sharp local pain; burning is uncommon unless the skin or subcutaneous issues are involved. Locations of these receptors include the skin, fascia, subcutaneous tissues, periosteum, endosteum, and joint capsules. 

Visceral pain receptors result in pain due to an injury of organ capsules and connective tissue. Pain can be localized or sharp. Visceral pain resulting from obstruction of a hollow organ is poorly localized, deep, cramping, and possibly referred to remote cutaneous sites. 

Pain Modulation and Transmission of Pain

Pain fibers enter the spinal canal and the spinal cord at the dorsal root ganglia and then synapse in the dorsal horn. Fibers cross to the other side and up the lateral columns to the thalamus and then to the cerebral cortex.

Repeat stimulus from a chronic pain condition may sensitize neurons in the dorsal horn of the spinal cord. As a result, a lesser peripheral stimulus may cause pain. Peripheral nerves and nerves at other levels of the CNS may become sensitized, producing long-term synaptic changes in cortical receptive fields that exaggerate pain perception.

When tissue is injured, substances are released, causing an inflammatory cascade that can sensitize peripheral nociceptors. These include chemical messengers such as serotonin, bradykinin, epinephrine, calcitonin gene-related protein, substance P, neurokinin A, and prostaglandin E2.

Pain signals are modulated at multiple points in both ascending and descending pathways by several neurochemical mediators, including endogenous opioids such as methionine enkephalin and beta-endorphin, and monoamines such as norepinephrine and serotonin. These mediators are thought to increase, sustain, shorten, or reduce the perception of and response to pain. They mediate the potential benefit of CNS-active drugs such as antidepressants, anticonvulsants, opioids, and membrane-stabilizing agents that interact with specific receptors and neurochemicals in treating chronic pain. 

Psychologic Factors Causing Pain

Psychogenic factors can modulate pain intensity. Emotion has a vital role in an individual's perception of pain. Patients in chronic pain have a high degree of psychological distress, often suffering from anxiety and depression. Patients with poorly explained pain may be incorrectly diagnosed with a psychiatric disorder rather than a legitimate underlying cause of the pain and are inappropriately denied pain relief, exacerbating the cycle of anxiety and depression.

Acute and chronic pain may impair concentration, memory, and thought processes. Pain may be multifactorial. Often the pain is due to both nociceptive components as well as neuropathic (due to nerve damage).

Psychologic factors may modulate pain. It affects how patients describe the pain and their response. The psychologic reaction to long-standing chronic pain interacts with CNS factors to induce changes in pain perception. Psychologic factors generate neural output that modulates neurotransmission along each pain pathway.

Histopathology

Chronic pain and opioids generally do not cause any specific histopathology in and of themselves. However, there is a diversity of histopathologic changes that can occur in the presence of improper/recreational parenteral administration of opioids. There may be chronic tissue damage present due to the original assault.[15]

Toxicokinetics

How each person processes a drug, including the rate of chemical absorption and what occurs to excrete and metabolize the compound once it has entered the body, is highly variable among individuals. Further, it may change with the degree and years of use.

Use disorder is a biological condition secondary to various environmental and genetic factors. Each human metabolizes drugs differently, and depending on their body's response; they may have little or no ability to discontinue the use of a drug.

History and Physical

For prescribers, it may be difficult to distinguish legitimate pain from drug-seeking behavior. Pain is often difficult to assess because patients may be impaired, and self-reporting may be inaccurate or difficult to obtain. The astute clinicians should rely on a combination of taking an accurate history, physical, and observation-based assessment.

Signs of Pain

• Activity changes: Appetite, increased fatigue, increased alcohol consumption, routines, and increased sleep.

• Facial expressions: Frowning, grimacing, and rapid blinking

• Body movements: Guarding, fidgeting, inactivity, motor restlessness, pacing, rigidity, rocking, and muscle tension

• Interpersonal interaction changes: Aggression, diminished sex drive, disruptive behavior, irritability, resisting care, and being withdrawn

• Mental status change: Anxiety, crying, confusion, depression, distress, irritability, and suicidal thoughts

• Verbalizations: Calling out, "I hurt everywhere," requesting help, sighing, and verbal abuse

Symptoms of Pain

• Diaphoresis

• Hypertension

• Pupil dilation

• Tachycardia

• Tachypnea 

Pain Evaluation Questions

• Character - A description of how the pain feels (dull, pinching, pounding, sharp, shooting, throbbing, pounding, stinging, burning).

• Radiation - Does the pain move anywhere?

• Site - Where is the pain? Where does it hurt?

• Onset - When did the pain start?

• Progression - Has the pain gotten worse or better since it started?

• Duration - For how long have you had the pain? Is it episodic?

• Severity - What is the pain severity (1 to 10)?

• Aggravating factors - Does anything make it worse, such as movement or a position?

• Relieving factors - Does anything you do or not do make the pain better? What treatments have you tried?

• Associative factors - The clinician should query other relevant questions from a review of systems based on the patient complaint.

Signs and Symptoms of Drug-seeking Behavior and Diversion

A common method to evaluate whether a patient is taking or misusing opioids is a random urine drug screen. Studies show that as high as 25% of patients prescribed opioids will randomly test negative. Patients discontinue opioid use due to remission of pain, side effects, lack of efficacy, and in some instances, opportunities to sell their medications.

Behaviors suggesting opioid drug use disorder

• Aggressive demand for more drugs
• Forging prescriptions
• Increased alcohol use and lack of control
• Increasing dose without permission
• Injecting or inhaling drugs prescribed for oral use
• Obtaining drugs from illegitimate sources
• Obtaining opioids from other providers
• Prescription loss
• Refusing to decrease pain medication dosage when stabilized
• Resisting medication change
• Requesting early refills
• Requesting specific medications
• Selling drugs
• Sharing prescriptions
• Stockpiling medications
• Using illegal drugs 

Evaluation

Evaluating a patient needing opioid analgesics requires a complete history, physical examination, laboratory, and radiographic studies. Depending on the circumstances, consultation with psychiatry should be a consideration, along with addiction experts, physical therapy, and occupational therapy.[16]

The clinicians must have a complete understanding of the patient's primary disease and any issues regarding the evaluation of proper use, potential side effects, and effectiveness of opioid use for chronic pain.

Overview Of Safe Prescribing Assessment Guidelines

Health professionals are trained to prescribe pain medications; unfortunately, controlled substances are commonly misused. The following provides an overview of the requirements for the safe prescribing of controlled substances. A more detailed discussion follows.

• History
  • Review chief complaint
  • Obtain current and past medical conditions
  • Obtain a list of current and past medications prescribed and dosage
  • Obtain patients' past medical records
  • Review the pain rating scale
  • Review family history, including alcohol, drug (illicit and non-illicit), and mental health (depression assessment)
  • Review social history including alcohol, drug (illicit and non-illicit), tobacco, mental health (depression assessment) as well as dependents, education, employment, living situation, marital status, and legal issues
  • Review opioid abuse risk assessment
  • Review of state prescription drug program
• Physical - perform a head-to-toe detailed physical exam
• Obtain a urine drug test

Chronic Pain Assessment

Standard blood work and imaging are not indicated for chronic pain, but the clinician can order them when specific causes of pain are suspected. This can be on a case-by-case basis. In some cases, urine toxicology is ordered to monitor compliance and exclude nonprescription drugs.

Psychiatric disorders can amplify pain, signaling making symptoms of pain worse.[17] Furthermore, comorbid psychiatric disorders, such as major depressive disorder can significantly delay the diagnosis of pain disorders.[18] Major depressive disorder and generalized anxiety disorder are the most common comorbid conditions related to chronic pain. There are twice as many prescriptions for opioids prescribed each year to patients with underlying pain and a comorbid psychiatric disorder compared to patients without such comorbidity.[19] Intuitively, this makes sense. For example, a patient suffering from depression often complains of fatigue, sleep changes, loss of appetite, and decreased activity. These symptoms can make their pain worse over time. It is also crucial to realize patients with chronic pain are at an increased risk for suicide and suicidal ideation.[20][21]

Simultaneously screening for depression is recommended for patients with chronic pain. The Minnesota Multiphasic Personality Inventory-II (MMPI-2) or Beck's Depression Scale are the two most commonly used tools. The MMPI-2 has been used more frequently for patients with chronic pain.[22][23]

Addiction Risk Assessment

The clinician should consider information from the history and physical, family members, the state prescription monitoring program, and screening tools to assess the risk of developing an untoward behavioral response to opioids.[9][24][25] Patients can be stratified to three risk levels:

1. Low-risk: standard monitoring, vigilance, and care
   • Objective signs and symptoms, localizable physical pathology
   • Confirmatory testing such as physical exam findings, CT, MRI, etc.
   • No individual or family history of substance abuse
   • At most, mild medical or psychologic comorbidity
   • Age < 45
   • High pain tolerance
   • Active coping strategies
   • Willingness to participate in multimodal therapy
   • Attempting to function at normal levels
2. Moderate-risk: additional level of monitoring and more frequent provider contact
   • Significant pain
   • Defined pathology with objective signs and symptoms
   • Confirmatory testing such as physical exam findings, CT, MRI, etc.
   • Moderate psychologic problems controlled by therapy
   • Moderate comorbidities are well controlled by medical therapy and are not affected by opioids
   • Mild opioid tolerance but not hyperalgesia without addiction or physical dependence
   • Individual or family history of substance abuse
   • Pain involving more than three regions of the body
   • Moderate levels of pain acceptance
   • Active coping strategies
   • Willing to participate in multimodal therapy
   • Attempting to function at normal levels
3. High-risk: intensive and structured monitoring, frequent follow-up contact, consultation with an addiction psychiatrist, and limited monthly prescription of short-acting opioids
   • Significant widespread pain
   • No objective signs and symptoms
   • Pain involves more than three body regions
   • Divergent drug-related behavior
   • Individual or family history of addiction, dependency, diversion, hyperalgesia, substance abuse, or tolerance
   • Major psychologic problems
   • Age >45
   • HIV-related pain
   • High levels of pain exacerbation
   • Poor coping strategies
   • Unwilling to participate in multimodal therapy
   • Not functioning at a normal lifestyle

Prescribing Opioids

Before prescribing opioids, complete a detailed patient history that includes:

• Indication requested for pain relief
• Location, nature, and intensity of pain
• Prior pain treatments and response
• Comorbid conditions
• Potential physical and psychological pain impact on the function
• Family support, employment, and housing
• Leisure activities, mood, sleep, substance use, and work
• Emotional, physical, or sexual abuse

When considering opioids, weigh the risks of abuse, addiction, adverse drug reactions, overdose, and physical dependence. If there are any special concerns, such as a history of substance abuse, consult a psychiatrist or addiction specialist. If current substance abuse, withhold prescribing until the patient is involved in an addiction treatment and monitoring program.

Assessment Tools [25]

Screening tools help determine the risk level and degree of monitoring and structure required for a treatment plan; however, their validity is not yet supported in the literature. Some examples of opioid tools include:

Brief Intervention Tool

Brief Intervention Tool is a 26-item "yes-no" questionnaire used to identify signs of opioid addiction or abuse. The items assess for problems related to drug use-related functional impairment.

CAGE, CAGE-AID, and CAGE-Opioid

CAGE (Cut down, Annoyed, Guilty, and Eye-opener) Questionnaire consists of four questions designed to assess alcohol abuse. CAGE-AID and CAGE-OPIOID are revised versions to evaluate the likelihood of current substance abuse.[26]

Current Opioid Misuse Measure (COMM)

The Current Opioid Misuse Measure is a 17-item patient self-reported assessment designed to identify abuse in chronic pain patients. It identifies aberrant behaviors associated with opioid misuse in patients already receiving long-term opioid therapy.

Diagnosis, Intractability, Risk, and Efficacy (DIRE) Tool

The Diagnosis, Intractability, Risk, and Efficacy is a clinician-rated questionnaire used to predict patient compliance with long-term opioid therapy. Patients scoring low are poor candidates for long-term opioids.

Mental Health Screening Tool

The Mental Health Screening Tool is a five-item screen that evaluates feelings of calmness, depression, happiness, peacefulness, and nervousness in the past month. A low score indicates that the patient should be referred to a pain management specialist.

Opioid Risk Tool

The Opioid Risk Tool is a five-item assessment to evaluate for aberrant drug-related behavior. It categorizes the patient into low, medium, or high levels of risk for aberrant drug-related behaviors based on question responses concerning previous alcohol, drug abuse, psychologic disorders, and other risk factors.

Pain Assessment and Documentation Tool (PADT)

Guidelines by the CDC, the Federation of State Medical Boards, and the Joint Commission stress documentation from both a quality and medicolegal perspective. The Pain Assessment and Documentation Tool (PADT) was designed to help the clinician document appropriate information.

Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)

The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a screen with questions addressing the history of alcohol or substance use, cravings, mood psychologic status, and stress. The SOAPP-R helps assess the risk level of aberrant drug-related behaviors and the monitoring level needed.

VIGIL

• Verification: Is this a responsible opioid user?
• Identification: Is the identity of this patient verifiable?
• Generalization: Do we agree on mutual responsibilities and expectations?
• Interpretation: Do I feel comfortable allowing this person to have controlled substances?
• Legalization: Am I acting legally and responsibly? 

Urine Drug Tests (UDT)

Urine drug tests evaluate the use of the medication prescribed and detect unsanctioned drug use. The CDC recommends drug testing before starting opioid therapy and at least annually.

One study suggests monitoring frequency based on risk level.[27] 

Testing is usually done with class-specific immunoassay drug panels; however, this may be followed with gas chromatography/mass spectrometry for specific metabolite detection. The test should identify the specific drug. If urine test results suggest aberrant opioid use, discuss the issue with a positive, supportive approach, and document the discussion.

Treatment / Management

Opioid analgesics should be prescribed for a limited period, typically several days to 3 to 4 weeks. The patient needs education on the risks and benefits of opioid treatment. Treatment goals should be set at the outset, including establishing the estimated time period, expected side effects, expected pain improvement, and avoiding more medication than prescribed without prior discussion with the provider. The therapy plan should include the drug selected, starting dosage, measures to track pain relief and associated therapies such as occupational or physical therapy.[28]

The initial patient dose should always be the lowest dose possible and, if necessary, gradually increase dose and frequency to achieve the desired effect. Dosing should be adjusted to achieve efficacy and tolerability. The patient should clearly understand the need for regular monitoring of progress and the need to frequently access the benefits and risks. The patient should be aware of complications such as constipation, fatigue, nausea, and risk of respiratory depression. The patient should make sure that only one prescriber should prescribe and monitor opioid analgesic therapy. Further, patients should understand that all prescribers need to be aware of opioid dosing so that other agents, such as CNS depressants, can be avoided, which may interact and cause additional respiratory depression.

When prescribing opioids, prescribers must be aware of the need for patient monitoring, equianalgesic dosing, and cross-tolerance. Prescribers need to consider the risks and benefits of short vs. long-acting/extended-release opioids.

All prescribers must be aware of federal and state opioid prescribing regulations.

Treatment Agreements and Informed Consent

Due to the inherent risks of opioids, the opioid prescription should include a treatment agreement or written informed consent for any treatment for more than a few days. Treatment agreements should include the following:

• Use disorder and misuse risks
• Drug interactions
• Physical dependence
• Motor impairment
• Short and long-term risks/benefits
• Side effects (constipation, rash, nausea, and respiratory depression)
• Tolerance

Prescribing practices should be stated, including:

• Frequency of refills
• Policy regarding early refills
• Procedure for lost or stolen medications

The agreement should also require the patient to limit opioid prescriptions to one physician and consent to random urine drug screens. Patient instruction should be to contact the prescriber for problems and make in-person appointments for refills. The agreement should discuss monitoring, the need for follow-up visits, storage, and disposal of opioids not used. The agreement should list potential reasons for the discontinuation of opioid therapy.

Overview Of Safe Treatment With or Without Controlled Substances

Generally, the provider should consider using a non-controlled substance to alleviate pain. However, if this fails, and the decision is made to prescribe a controlled substance, before beginning therapy, two important documents should be obtained:

1. Informed consent - should include the drug prescribed, risks (overdose, respiratory depression, dependence, drug interaction, death, and if the female is at risk of neonatal withdrawal syndrome), benefits (pain relief), desired goal or outcome, expected length, and follow-up care. Those goals should be collaborative.
2. Patient-provider agreement - This is signed by the patient and provider and includes responsibilities of the patient and provider, goals of controlled substance use, and the consequences of nonadherence with the treatment plan.
   • The first prescription is a trial with a determined follow-up appointment
   • Includes pill counts if needed
   • Refills and how they are handled
   • Use of a single provider for all controlled substances
   • Exit strategy when goals are achieved

Mild pain - start with acetaminophen or nonsteroidal anti-inflammatory drug, or in some cases, both. Whenever possible, consider alternative pain relief therapies, including physical therapy, massage, electrotherapy stimulation, Yoga, biofeedback, and acupuncture.

Moderate pain - start with a mild opioid such as codeine or tramadol. Also, consider supplemental alternative pain relief therapies.

Severe pain - start with a more potent opioid such as hydrocodone, hydromorphone, oxycodone, or morphine. Use immediate-release controlled substances with a half-life of 2 to 4 hours until the dose is stabilized. Adjust dose initially every 2-3 days. Extended-release or long-acting opioids with a half-life of 8-12 hours in the same family are added later. Also, consider supplemental alternative pain relief therapies.

Chronic Pain

Healthcare professionals who treat patients with chronic pain should understand best practices in opioid prescribing, approaches to pain assessment, pain management modalities, and appropriate use of opioids for pain control. Pharmacologic and nonpharmacologic approaches should be evaluated. Patients with moderate-to-severe chronic pain who have been assessed and treated with non-opioid therapy without adequate pain relief are candidates for opioid therapy. Initial treatment should be a trial of therapy, not a definitive course of treatment. The CDC has issued updated guidance on prescribing opioids for chronic pain. These guidelines address when to initiate or continue opioids for chronic pain, opioid selection, dosage, duration, follow-up, and discontinuation, assessing risk, and addressing opioid use harm.

Pain Referral

Recommendations are to refer a patient to pain management in the case of debilitating pain which is unresponsive to initial therapy. The pain may be located at multiple locations, requiring multimodal treatment or increases in dosages for adequate pain control or invasive procedures to control pain. Treatment of both pain and a comorbid psychiatric disorder leads to a more significant reduction of both pain and symptoms of the psychiatric disorder.[29] Pain may also worsen concurrent depression; thus, the treatment of pain has been demonstrated to improve the responses to the treatments for depression.[30] There are multiple pharmacological, adjunct, nonpharmacological, and interventional treatments for chronic, severe, and persistent pain. 

Pharmacologic Options

The list of pharmacological options for chronic pain is extensive. This list includes non-opioid analgesics such as nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, and aspirin. Medications such as tramadol, opioids, and antiepileptic drugs (gabapentin or pregabalin) can be useful. Furthermore, antidepressants such as tricyclic antidepressants and SNRIs, topical analgesics, muscle relaxers, N-methyl-d-aspartate (NMDA) receptor antagonists, and alpha 2 adrenergic agonists are also possible pharmacological therapies. 

Treatment response can differ between individuals, but treatment is typically done in a stepwise fashion to reduce the duration and dosage of opioid analgesics. However, there is no singular approach appropriate for treating pain in all patients.[31]

Major Pain Types and Treatment Options

Musculoskeletal

Chronic musculoskeletal pain is nociceptive pain. The treatment of such pain is in a stepwise approach but includes a combination of non-opioid analgesics, opioids, and nonpharmacological therapies. First-line therapy would be acetaminophen or NSAIDs. Both are effective for osteoarthritis and chronic back pain.[32][33][34] However, NSAIDs are relatively contraindicated in patients with a history of heart disease or myocardial infarction, renal disease, or patients on anticoagulation or with a history of ulcers.[35][36] There is limited evidence of which NSAID to use over another. One nonsteroidal anti-inflammatory pharmacological agent may have a limited effect on a patient's pain, while another may provide adequate pain relief. The recommendations are to try different agents before moving on to opioid analgesics.[37] Failure to achieve appropriate pain relief with either acetaminophen or NSAIDs can lead to considering opioid analgesic treatment. 

Opioids are considered a second-line option; however, they may be warranted for pain management for patients with severe persistent pain or neuropathic pain secondary to malignancy.[38] There have been conflicting results on the use of opioids in neuropathic pain. However, for both short-term and intermediate use, opioids are often used to treat neuropathic pain.[39] Opioid therapy should only start with extreme caution for patients with chronic musculoskeletal pain.[40] Side effects of opioids are significant and frequent and may include opioid-induced hyperalgesia, constipation, dependence, and sedation. For chronic musculoskeletal pain they are not superior to non-opioid analgesics.[41][42]

Administration of opioid analgesics should be reserved for when alternative pain medications have not provided adequate pain relief or are contraindicated and when pain impacts the patient's quality of life. The potential benefits outweigh the short and long-term effects of opioid therapy. The patient must make an informed choice before starting opioid treatment after discussing the risks, benefits, and alternatives to opioids.[41][43][44] Patients taking opioids at greater than 100 morphine milligram equivalents per day are at significantly increased risk of side effects. Side effects of opioids such as respiratory compromise will increase as the dosages increase. Patients with chronic pain could benefit from a therapy program designed to wean them from opioid analgesics to a safer dosage.[45][46] Long-acting opioids should only be used over short-acting opioids in the setting of disabling pain, causing severe impairment to quality of life.[47]

There is an estimated 78 percent risk of an adverse reaction to opioids, such as constipation or nausea, while there is a 7.5 percent risk of developing a severe adverse reaction ranging from immunosuppression to respiratory depression.[48] Patients with chronic pain who meet the criteria for the diagnosis of opioid use disorder should receive the option of buprenorphine to treat their chronic pain. Buprenorphine is a considerably better alternative for patients with very high daily morphine equivalents who have failed to achieve adequate analgesia.

Different types of pain also warrant different treatments. For example, chronic musculoskeletal back pain would be treated differently from severe diabetic neuropathy. A combination of multiple pharmacological therapies is often necessary to treat neuropathic pain. Less than 50% of patients with neuropathic pain will achieve adequate pain relief with a single agent.[49] Adjunctive topical therapy, such as lidocaine or capsaicin cream, can also be utilized.[50][51]

Neuropathic

The initial treatment of neuropathic is often with gabapentin or pregabalin. These are calcium channel alpha 2-delta ligands. They are indicated for postherpetic neuralgia, diabetic neuropathy, and mixed neuropathy.[52] There is limited evidence in using other antiepileptic medications to treat chronic pain, where many of these, such as lamotrigine, have a more significant side effect profile. The exception is carbamazepine in treating trigeminal neuralgia and other types of chronic neuropathic pain.[53][54]

Alternatively, antidepressants such as dual reuptake inhibitors of serotonin and norepinephrine (SNRI) or tricyclic antidepressants (TCA) can is an option. Antidepressants are beneficial in treating neuropathic pain, central pain syndromes, and chronic musculoskeletal pain. For neuropathic pain, antidepressants have demonstrated a 50 percent reduction in pain. Fifty percent is a significant reduction, considering the average decrease in pain from various pain treatments is 30%.[55][56]

The serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine is a useful treatment for treating chronic pain, osteoarthritis, and fibromyalgia.[57] Furthermore, the efficacy of duloxetine in the treatment of comorbid depression is comparable to other antidepressants.[58][55] Venlafaxine is an effective treatment for neuropathic pain, as well.[59] A TCA can also be utilized, such as nortriptyline. TCA medications may require six to eight weeks to achieve their desired effect.[38]

Adjunctive topical agents such as topical lidocaine are a useful treatment for neuropathic pain and allodynia, as in postherpetic neuralgia.[60][61] Topical NSAIDs have been shown to improve acute musculoskeletal pain, such as a strain, but are less effective in chronic pain. Yet, topical NSAIDs are more effective than controls in treating pain related to knee osteoarthritis.[62][63] Separately, topical capsaicin cream is an option for chronic neuropathic or musculoskeletal pain unresponsive to other treatments.[64] Botulinum toxin has also demonstrated effectiveness in the treatment of postherpetic neuralgia.[65] The use of cannabis is also an area of interest in pain research. There is some evidence that medical marijuana can effectively treat neuropathic pain, while the evidence is currently limited in treating other types of chronic pain.[66]

Additional Nonpharmacologic Options

The list of nonpharmacological therapies for chronic pain is extensive. Nonpharmacological options include heat and cold therapy, cognitive behavioral therapy, relaxation therapy, biofeedback, group counseling, ultrasound stimulation, acupuncture, aerobic exercise, chiropractic, physical therapy, osteopathic manipulative medicine, occupational therapy, and TENS units. Interventional techniques can also be utilized in the treatment of chronic pain. Spinal cord stimulation, epidural steroid injections, radiofrequency nerve ablations, botulinum toxin injections, nerve blocks, trigger point injections, and intrathecal pain pumps are some procedures and techniques commonly used to combat chronic pain. TENS units' efficacy has been variable, and the results of TENS units for chronic pain management are inconclusive.[67] Deep brain stimulation is for post-stroke and facial pain as well as severe, intractable pain where other treatments have failed.[68] There is limited evidence of interventional approaches to pain management. For refractory pain, implantable intrathecal delivery systems are an option for patients who have exhausted all other options. Cognitive-behavioral has been found to be particularly helpful for pelvic pain syndromes.[69] 

Spinal cord stimulators are an option for patients with chronic pain who have failed other conservative approaches. Most commonly, spinal cord stimulators are placed following failed back surgery but can also be an option for other causes of chronic pain such as complex regional pain syndrome, painful peripheral vascular disease, intractable angina, painful diabetic neuropathy, and visceral abdominal and perineal pain.[70][71][72][73][74] Spinal cord stimulators have shown a 50% reduction in pain compared to continued medical therapy.[75]

Differential Diagnosis

Examples of conditions that may require acute or chronic opioid analgesic use include:

• Abdominal epilepsy
• Abdominal migraines
• Achilles tendon injuries
• Adhesive capsulitis
• Adenomyosis
• Adhesions
• Adnexal cysts
• Brachial neuritis
• Cancer
• Carpal tunnel syndrome
• Cervical disc disease
• Cervical myofascial pain
• Cervical spondylosis
• Cervical sprain and strain
• Complex regional pain syndromes
• Cervical stenosis
• Chronic pelvic pain
• Chronic visceral pain
• Chronic fatigue syndrome
• Colitis
• Dyspareunia
• Endocervical polyps
• Endometriosis
• Fibromyalgia
• Gastrointestinal problems
• Hernias
• Irritable bowel syndrome
• Lateral epicondylitis
• Lumbar degenerative disk disease
• Lumbar facet arthropathy
• Lumbar spondylolysis and lumbar spondylolisthesis
• Mechanical back strain
• Medial epicondylitis
• Mononeuropathy and nerve entrapment
• Morton neuroma
• Myofascial pain
• Neoplasia of the spinal cord
• Neoplastic brachia plexopathy
• Neoplastic lumbosacral plexopathy
• Osteoarthritis
• Osteoporosis
• Ovarian retention syndrome
• Pelvic floor pain syndrome
• Piriformis syndrome
• Radiation-induced brachial plexopathy
• Radiation-induced lumbosacral plexopathy
• Rectus abdominis pain
• Rotator cuff disease
• Pelvic varicosities
• Plantar fasciitis
• Reproductive system disorders
• Spasticity
• Substance abuse
• Thoracic outlet syndrome
• Traumatic brachial plexopathy
• Trochanteric bursitis
• Uterine leiomyomas
• Urinary system disorders
• Urolithiasis
• Vulvodynia 

Treatment Planning

Opioid analgesics should be prescribed for a limited period, typically several days to 3-4 weeks. Patient education on the risks and benefits of opioid analgesic treatment should always be a feature of opioid prescribing. The goal of treatment should be defined at the outset, including establishing the estimated period for opioid therapy, expected side effects, expected pain improvement, and avoidance of using more medication than prescribed without prior discussion with the provider. The treatment plan should include the drug selected, starting dosage, measures to track pain relief, and associated therapies such as occupational or physical therapy, which can help decrease pain sensation.

Opioid therapy should begin as a trial for a pre-defined period, usually less than 30 days. Treatment goals should be established prior to the initiation of opioid therapy. These include the level of relief of pain, anxiety, depression, and the return of function while avoiding unnecessary opioid use. The plan should include therapy selection, progress measures, and additional consultations, evaluations, referrals, and therapies. The provider should:

• Start at the lowest possible dose and then titrate to effect
• Start with short-acting opioid formulations
• Discuss the need for frequent risk/benefit assessments
• Be instructed in the signs and symptoms of respiratory depression
• Reassess risk/benefit with each dose increase
• Decisions to titrate dose to 90 mg or more morphine equivalent dose should be justified
• Be knowledgeable of federal and state opioid prescribing regulations
• Be knowledgeable of patient monitoring, equianalgesic dosing, and cross-tolerance with opioid conversion
• Augment treatment with nonopioid or, if necessary immediate-release opioids over long-acting opioids
• Taper opioid dose whenever possible

Consent and Treatment

The patient must consent to the course of therapy and understand all implications of their medical regimen.[9]

The opioid prescription should include documented informed consent and a treatment agreement addressing:

• Drug interactions
• Physical dependence
• Side effects
• Tolerance
• Physical dependence
• Driving and motor skill impairment
• Limited evidence of long-term benefit
• Addiction, dependence, misuse
• Risk/benefit profile of the drug prescribed
• Signs/symptoms of overdose

Prescribing policies should be clearly described, including policies regarding the number and frequency of refills and procedures for lost or stolen medications.

Patient and Physician Treatment Agreement

• The patient should agree to use medications safely, avoid "prescriber shopping," and consent to urine drug testing.
• The prescriber should agree to address problems, follow-up visits, and scheduled refills.

Reasons for opioid therapy change or discontinuation should be listed. Agreements can also include follow-up visits, monitoring, and safe storage and disposal of unused drugs. If the patient does not speak English, an interpreter should be used.

Discontinuing Opioid Therapy

Discontinuing opioid therapy should be based on a physician-patient discussion. Opioids should be discontinued when the pain has resolved, side effects develop, analgesia is inadequate, quality of life is not improved, deterioration of function, or evidence of aberrant medication use. Opioids should be tapered slowly, and an addiction specialist should manage withdrawal.

Toxicity and Adverse Effect Management

The toxicities of prescribed opioid analgesics are avoidable with appropriate daily dosing, and opioid analgesics are not combined with other central nervous system depressants, e.g., ethanol, diazepam, and phenobarbital.[76]

Constipation is not an uncommon side effect of opioid analgesics, but this is manageable with the careful use of laxatives. If laxative treatment is ineffective, then drugs like methylnaltrexone can help relieve constipation while maintaining pain control with the opioid analgesic, e.g., morphine.

Adverse Reactions to Opioids

Common adverse reactions include drowsiness, respiratory depression, confusion, dizziness, nausea/vomiting, headache, fatigue, pruritus, pinpoint pupils, constipation, and urinary retention. Because opioids induce euphoria at higher doses than prescribed, these drugs are at high risk for abuse and addiction. Long-term drug tolerance, hyperalgesia, or increased sensitivity to pain caused by damage to nociceptors or peripheral nerves may occur.

Depressants 

Hypnotics, sedatives, and tranquilizers treat anxiety and sleep disorders. These drugs increase the inhibitory activity of the neurotransmitter gamma-aminobutyric acid by inhibiting overall brain activity, producing a calming effect. Examples of depressants include:

Anxiety

Benzodiazepines are schedule IV  medications and include drugs such as alprazolam, clonazepam, diazepam, estazolam, and triazolam. They are used to treat anxiety, stress reactions, muscle spasms, and sleep disorders. They should be used short-term with caution as they have a high risk of addiction, dependence, and tolerance. The combination of benzodiazepines and opioids should be avoided due to the potential for addiction and respiratory depression.

All CNS depressants can cause confusion, drowsiness, and poor coordination. Avoid stopping these medications abruptly due to the risk of dangerous or fatal withdrawal symptoms or seizures. Benzodiazepine overdose is treated with a benzodiazepine antagonist, flumazenil, which can be administered via IV and provides rapid reversal.

For anxiety treatment, there are available options that are less risky such as buspirone, which binds to serotonin and dopamine D2 receptors. It causes minimal drowsiness and has less abuse potential.

Sleep

Whenever possible, prescribers should select non-benzodiazepine sleep medications such as eszopiclone, zolpidem, and zaleplon, which act on GABA type A receptors in the brain but with fewer side effects and less risk of dependence, and they are schedule IV. Other options include melatonin and ramelteon.

Stimulants

Stimulants often abused include dextroamphetamine, methamphetamine, and methylphenidate. They work by enhancing the effects of the neurotransmitters norepinephrine and dopamine in the brain. While stimulants increase alertness, cognition, energy, and motivation, they also induce vascular constriction resulting in elevated heart rate and blood pressure, increased respiratory rate, dilated airway, elevated blood glucose, and insomnia. They are used to treat attention-deficit hyperactivity disorder, narcolepsy, and rarely depression. Misuse can cause euphoria due to increased dopamine activity in the brain. Abrupt withdrawal can cause depression, fatigue, and insomnia. Abuse or overdose may cause hostility, paranoia, psychosis, hyperthermia, arrhythmias, cardiovascular arrest, or seizures. They are classified as schedule II drugs.

A slightly safer alternative is modafinil, which works to block the reuptake of dopamine and other neurotransmitters. It has a slightly safer profile and is classified as schedule IV.

The American Society of Interventional Pain Physicians guidelines recommends monitoring opioid adherence, abuse, and nonadherence through urine drug tests and monitoring programs.

The treatment plan for opioid use in chronic pain should include frequent assessment of pain level, origin, and function. If there is a dosage change or agent, the frequency of patient visits should be increased. Chronic response to opioids should be monitored by evaluating the "5 As."

• Affect
• Aberrant drug-related behaviors
• Activities of daily living
• Adverse or side effects
• Analgesia

Signs and symptoms, if present, that suggests treatment goals are not being achieved include:

• Decreased appetite
• Excessive sleeping or day/night reversal
• Impaired function
• Inability to concentrate
• Mood volatility
• Lack of involvement with others
• Lack of re-engaging in life
• Lack of hygiene

The decision to change, continue, or terminate opioid therapy is based on achieving treatment objectives without adverse effects. Physicians, wherever possible, should work with pharmacists. 

Acute Overdose Management

Accidental or deliberate overdose is always a risk factor in patients taking opioids. The patient and family should be instructed in the signs and symptoms of an overdose and basic emergency management until paramedics' arrival.[77]

The immediate response to overdose management is to secure the airway and breathing; however, survival is heavily dependent upon the rapid administration of an opioid antagonist. Many states allow naloxone distribution to the public. Licensed healthcare providers may prescribe opioid antagonists for at-risk individuals, relatives, or caregivers. Emergency medical service personnel, peace officers, and firefighters also have the drug available.

While opioid antagonists such as naloxone, naltrexone, and nalmefene are available, acute overdoses are usually treated with naloxone as it quickly reverses opioid-related respiratory depression. Naloxone competes with opioids at receptor sites in the brain stem, reversing desensitization to carbon dioxide and preventing respiratory failure. 

The naloxone dose is 0.4 to 2 mg administered intravenously, intramuscularly, or subcutaneously. The dose may be repeated every 2 to 3 minutes. Naloxone is available in pre-filled auto-injection devices. Advanced Cardiac Life Support protocols should be continued while naloxone is being administered. Naloxone is also available in a nasally administered dosage form.

Prognosis

Physicians should carefully evaluate and treat patients for acute pain syndromes and use opioid analgesics at the appropriate dose and only on a short-term basis. Those patients requiring long-term pain control should obtain a referral to a pain management specialist.

Current chronic pain treatments can result in an estimated 30% decrease in a patient's pain scores.[31] A thirty percent reduction in pain can significantly improve a patient's function and quality of life.[78] However, the long-term prognosis for patients with chronic pain demonstrates reduced function and quality of life. Improved outcomes are possible in patients with chronic pain and improve with the treatment of comorbid psychiatric illness. Chronic pain increases patient morbidity and mortality and increases rates of chronic disease and obesity. Patients with chronic pain are also at a significantly increased risk for suicide compared to the regular population.

Spinal cord stimulation results in inadequate pain relief in about 50% of patients. Tolerance can also occur in up to 20 to 40 percent of patients. The effectiveness of spinal cord stimulation decreases over time.[79] Similarly, patients who develop chronic pain and are dependent on opioids often build tolerance over time. As the amount of morphine milligram equivalents increases, the patient's morbidity and mortality also increase.

Ultimately, prevention is critical in the treatment of chronic pain. If acute and subacute pain receives appropriate treatment and chronic pain can be avoided, the patient will have limited impacts on their quality of life. 

Complications

In the United States, two of the critical complications and public health concerns of opioid analgesics are overdoses and opioid use disorder.

Chronic pain leads to significantly decreased quality of life, reduced productivity, lost wages, worsening chronic disease, and psychiatric disorders such as depression, anxiety, and substance abuse disorders. Patients with chronic pain also have a significantly increased risk for suicide and suicidal ideation.

Many medications often used to treat chronic pain have potential risks and side effects, and possible complications associated with their use.

Acetaminophen is a standard pharmacological therapy for patients with chronic pain. It is taken either as a single agent or in combination with an opioid analgesic. The hepatotoxicity occurs with acetaminophen when exceeding four grams per day.[80] It is the most common cause of acute liver failure in the United States.[81] Furthermore, hepatotoxicity can occur at therapeutic doses for patients with chronic liver disease.[82]

Frequently used adjunct medications such as gabapentin or pregabalin can cause sedation, swelling, mood changes, confusion, and respiratory depression in older patients who require additional analgesics.[83] These agents require caution in elderly patients with painful diabetic neuropathy. Also, gabapentin or pregabalin, combined with opioid analgesics, has been shown to increase the rate of patient mortality.[84]

Duloxetine can cause mood changes, headaches, nausea, and other possible side effects and should be avoided in patients with a history of kidney or liver disease.

Feared complications of opioid therapy include addiction as well as overdose resulting in respiratory compromise. However, opioid-induced hyperalgesia is also a significant concern. Patients become more sensitive to painful stimuli while on chronic opioids.[85] The long-term risks and side effects of opioids include constipation, tolerance, dependence, nausea, dyspepsia, arrhythmia (methadone treatment QTc prolongation), and opioid-induced endocrine dysfunction, which can result in amenorrhea, impotence, gynecomastia, and decreased energy and libido. Also, there appears to be a dose-dependent risk of opioid overdose with increasing daily milligram morphine equivalents.

Complication rates for spinal could stimulators are high, ranging from five to 40%.[86][87] Lead migration occurs most commonly, causing inadequate pain relief and requiring revision and anchoring.[88][89] Lead movement often occurs in the cervical region of the spinal cord, given an increased range of motion of the cervical vertebra.[90][91] Spinal cord stimulator lead fracture can occur in up to 9% of placements.[92][93] Seromas are also very common and may require surgical incision and drainage.[94][86] The risk of infection following a spinal cord stimulator placement is between 2.5 and 12 percent.[95][96] Lastly, direct spinal cord trauma could occur. The most significant infectious complication would be a spinal cord abscess. A dural puncture can cause a post-dural headache in up to 70% of patients.[97][98][94] A spinal epidural hematoma is the most significant adverse to spinal cord stimulator placement. This emergency would require immediate neurosurgical decompression of the hematoma. The incidence of a spinal epidural hematoma is 0.71%.[99]

Drug Diversion and Drug Seeking

Unfortunately, some individuals seek prescribed opioids for illicit purposes due to addiction or financial gain. Prescription opioids may be obtained from a friend or relative, purchased from a black market drug dealer, obtained by prescriber shopping and acquiring drugs from multiple prescribers, and theft from clinics, hospitals, or pharmacies.[24]

• Aggressive demands for more opioids
• Asking for opioids by name
• Behaviors suggesting opioid use disorder
• Forged prescriptions
• Increased alcohol use
• Increasing medication dose without provider permission
• Injecting oral medications
• Obtaining medications from nonmedical sources
• Obtaining opioids from multiple providers
• Prescription loss or theft
• Reluctance to decrease opioid dosing
• Resisting medication change
• Requesting early refills
• Selling prescriptions
• Sharing or borrowing similar medications
• Stockpiling medications
• Unsanctioned dose escalation
• Using illegal drugs
• Using pain medications to treat other symptoms

Drug Diversion Interventions

Prescribers and dispensers can take several precautions to avoid drug diversion. Some approaches include:

• Communication among providers and pharmacies to prevent "prescriber shopping"
• Educate patients on the dangers of sharing opioids 
• Encourage patients to keep opioid medications in a private place
• Encourage patients to refrain from public disclosure of opioid use
• Report patient prescribing to a state-level central database if available

If a patient is suspected of drug-seeking or diversion, consider the following actions:

• Inquire about prescription and illicit drug use
• Obtain a urine drug screen
• Perform a thorough examination
• Perform pill counting
• Prescribe smaller quantities of the opioid

If a patient is abusing prescribed opioids, this is a violation of the treatment agreement. The provider may then choose to discharge the patient from their practice. If the relationship is terminated, the provider must do it legally. The provider should avoid patient abandonment, ending a relationship with a patient without considering the continuity of care, and without providing notice to the patient. To avoid abandonment charges, the patient must be given enough advanced warning to allow them to secure another physician and facilitate the transfer of care.

Patients with a substance misuse problem or addiction should be referred to a pain specialist. Theft or loss of controlled substances should be reported to the Drug Enforcement Administration. The activity should be documented and reported to law enforcement if drug diversion has occurred.

Consultations

Most clinicians should have the knowledge and ability to evaluate and treat patients for acute pain syndromes and use opioid analgesics on a short-term basis. Those patients that require long-term pain control may receive a referral to a pain specialist.

All clinicians who regularly prescribe opioids should be familiar with opioid use disorder treatment and be aware of local referral options. They should seek a referral to specialists when use disorder, pain, psychiatry, or mental health assistance is needed.

If a patient has a use disorder, providers should refer the patient to both an addiction/use disorder and pain management professional. Unfortunately, clinicians specializing in pain and use disorders are rare, and it is difficult for most clinicians to find appropriate referrals.

Documentation is of particular importance when opioid analgesic prescribing is involved. Clinicians should maintain accurate, complete, and up-to-date records, including copies of all prescription orders for all controlled substances, opioid contracts, instructions given for use, and the name, telephone, and address of the pharmacy dispensing them. Accurate medical records demonstrate that the prescription and management of an opioid analgesic prescription was medically necessary. Thorough medical records protect the prescriber and the patient.

Deterrence and Patient Education

Many nations have instituted efforts to minimize the quantities of opioid analgesics prescribed. Hopefully, this will decrease opioid use disorder and the morbidity and mortality associated with opioid analgesic abuse.

Involvement of Patient and Family

The patient and family can assist in making informed decision-making regarding continuing or discontinuing opioid therapy. Family members are often aware of when a patient is depressed and less functional. Questions to ask the family include:

• Is the patient's day focused on taking opioid pain medication? 
• What is the frequency of pain medication?
• Does the patient have any other alcohol or drug problems?
• Does the patient avoid activity?
• Is the patient depressed?
• Is the patient able to function? 

What To Teach A Patient Taking Opioids

• Avoid driving or operating power equipment
• Avoid stoping opioids suddenly
• Avoid taking other drugs that depress the respiratory system as alcohol, sedatives, and anxiolytics
• Contact prescribing if pain medication is not adequate for relief
• Destroy opioids based on product-specific disposal information (usually flushing down the toilet or mixing with cat litter or coffee grounds)
• Do not chew tables
• Do not share opioids with friends or family
• Follow the prescribed dosing regimen
• Provide product-specific information
• Take opioids only as prescribed

Pearls and Other Issues

Maintain Accurate Medical Records Regarding Opioid Analgesic Prescriptions

All clinicians should maintain accurate, complete, and current medical records, including:

• All communication should be noted
• Notes should be clear, documenting dose adjustments, effectiveness, and any adverse effects
• Describe adherence or lack of adherence to treatment
• Urine drug screen results
• Concerning behaviors
• Family interactions
• In particular, document any decisions regarding the termination of care 

Federal and State Laws[100]

Several regulations and programs at the federal and state levels reduce prescription opioid abuse, diversion, and overdose. These laws require:

• Immunity from prosecution for individuals seeking assistance during an overdose
• Pain clinic oversight
• Patient identification prior to dispencing
• A physical examination before prescribing opioids
• Prescription limits
• A prohibition from obtaining controlled substance prescriptions
• Tamper-resistant prescriptions

Federal Laws

The U.S. Drug Enforcement Administration (DEA) sets national standards for controlled substances. Drug scheduling was mandated under The Federal Comprehensive Drug Abuse Prevention and Control Act of 1970. The law addresses controlled substances within Title II. The DEA maintains a list of controlled medications and illicit substances categorized from scheduled I to V. The five categories have their basis on the medication's proper and beneficial medical use and the medication's potential for dependency and abuse. The purpose of the law is to provide government oversight over the manufacturing and distribution of these substances. Prescribers and dispensers must have a DEA license to supply these drugs. The licensing provides links to users, prescribers, and distributors.[101][102][103]

The schedules range from Schedule I to V. Schedule I drugs are considered to have the highest risk of abuse, while Schedule V drugs have the lowest potential for abuse. Other factors considered by the DEA include pharmacological effect, evidenced-based knowledge of the drug, risk to public health, trends in the use of the drug, and whether or not the drug has the potential to be made more dangerous with minor chemical modifications. 

 It is essential to understand the DEA controlled-substance scheduling both to ensure adequate caution when prescribing medications with high abuse potential and also to ensure against prescribing outside of one's authority.[104][105]

The Controlled Substances Act has great potential to improve patient safety by providing federal oversight for drugs with a high potential for abuse. Providers of scheduled substances (physicians, dentists, podiatrists, advanced practitioners) may have links to the distribution of these substances. They are required to have a DEA license and record prescription of scheduled drugs.[106][107] This licensing prevents overprescribing and obligates providers to be wary of potential drug-seeking patients. The dispenser must also be aware of a patient's medication history and be mindful of the potential for polypharmacy if a patient seeks multiple providers.[108] The current opioid epidemic is a time where federal oversight and interdisciplinary coordination can potentially reduce harm to patients prescribed scheduled drugs drastically. However, it will take additional time and evaluation to determine if drug scheduling reduces abuse, addiction, and overdose.[109][110]

Enhancing Healthcare Team Outcomes

A common concern of patients is how effectively the healthcare provider treats their pain. The healthcare team, e.g., physicians, nurses, pharmacists, etc., must work together to assess and treat the patient's pain appropriately and avoid addiction. The prescriber should always initiate therapy on the lowest dose possible, and then the dose and frequency should be gradually increased to achieve the desired effect, efficacy, and tolerability. The prescriber should ensure that the patient clearly understands the need for regular monitoring and for the need to frequently assess the benefits and risks of treatment. The patient should be aware of complications such as constipation, fatigue, nausea, and the risk of respiratory depression.

The patient should ensure that only one healthcare provider prescribes and monitors the opioid analgesic therapy. Further, patients should understand that all healthcare providers are aware of any current opioid analgesics to avoid polypharmacy and medication interaction with other prescriptions. This can help reduce the chance of medication-induced CNS depression or respiratory depression. The healthcare team must be aware of federal and state opioid analgesic prescribing and dispensing regulations. Due to the inherent risks of opioid analgesic abuse, any treatment or opioid analgesic prescription of greater than a few days duration should include a treatment agreement or written informed consent.

The agreement should also require the patient to have only a single physician or appropriately licensed healthcare provider prescribe their opioid analgesic prescriptions and consent to random urine drug screens. The patient should receive counsel to contact the healthcare team for problems and make in-person appointments for refills. The agreement should discuss monitoring, need for follow-up visits, storage, and disposal of opioid analgesics not used. The agreement should list possible reasons for the discontinuance of opioid analgesic therapy.[106][107]

Chronic pain is a significant condition affecting millions of people and is an important public health concern with considerable morbidity and mortality and associated with opioid drug diversion and misuse. Thus chronic pain is best managed with an interprofessional approach. Managing chronic pain requires an interprofessional team of healthcare professionals, including a primary care physician, nursing team, pharmacist, and pain medicine specialists. Without proper management, the patient's quality of life can have a deleterious impact. The evaluation and treatment of such patients are paramount, but health professionals must work as a team to avoid drug diversion and misuse.

Chronic pain correlates with several severe complications, including severe depression and suicide attempts, and ideation. The lifetime prevalence for chronic pain patients attempting suicide attempts was shown to be between 5% and 14%; suicidal ideation was approximately 20%.[20] These complications often require psychiatric intervention and advanced pharmacological or interventional therapies. Severe symptoms must receive treatment immediately, leading to an increase in healthcare costs. It is of the utmost importance to identify the risk factors and perform a thorough assessment of the patient with chronic pain as well as monitor for progression of symptoms. A team approach is an ideal way to limit the effects of chronic pain and its complications. 

• The first step is to evaluate a patient with acute pain by the primary care provider to prevent the progression of chronic pain.
• Conservative management of chronic pain should commence when symptoms are mild or moderate, including physical therapy, cognitive-behavioral therapy, and pharmacological management.
• A pharmacist or other expert knowledgeable in the medications frequently utilized to treat chronic pain should evaluate the medication regimen to include medication reconciliation to preclude any drug-drug interactions and alert the healthcare team regarding any concerns.
• The patient should regularly follow up with a primary care provider and pain specialists to assess and effectively treat the patient's pain.
• Clinicians must address comorbid psychiatric disorders. This action may require the involvement of a psychiatrist, depending on the severity of the patient's symptoms.
• If symptoms worsen on follow-up or if there is a concerning escalation of pharmacological therapy such as with opioids, a referral to a pain medicine specialist merits consideration.
• If the patient has exhausted various pharmacological and nonpharmacological treatment options, interventional procedures can be considered.
• If the patient expresses concern for suicidal ideation or plan at any time, an emergent psychiatric team should evaluate the patient immediately.
• Patients who have developed opioid dependence secondary to pharmacological therapy should be offered treatment, possibly referral for addiction treatment or detoxification if indicated. The patient should be placed on a medication weaning schedule or possibly medications to treat opioid dependence.
• Based on CDC recommendations, patients on high-dose opioid medications or patients with risk factors for opioid overdose (e.g., obesity, sleep apnea, concurrent benzodiazepine use, etc.) should receive naloxone at home for the emergent treatment of an unintentional overdose.

The interprofessional team should openly discuss and communicate clearly about the management of each patient so that the patient receives optimal care delivery. This area is where nurses and pharmacists can play a crucial role by verifying patient adherence to the treatment plan and monitoring progress (or lack thereof) with the present treatment plan. Nurses and pharmacists can help monitor for adverse medication side effects and concerns regarding diversion or misuse of opioids and communicate any areas of concern to the treating clinicians. Effective, open interprofessional communication and accurate documentation of findings for access by all team members are crucial in managing chronic pain and minimizing the adverse effects of chronic pain in the patient. [Level 2] 

Interprofessional Team Case Study

CC: Syncope and Confusion

HPI: A 70-year-old confused female arrives in the trauma after she was found passed on the bathroom floor near the toilet. The husband reports a history of morbid obesity, diabetes mellitus, kidney disease, and chronic right hip pain, for which she has been scheduled for prosthetic hip surgery replacement that has been delayed to get her weight under control. She has been prescribed a combination of hydrocodone and acetaminophen to allow control of the pain enough for ambulation and daily pool exercises. Lately, the pain has been getting worse, and the husband mentions that occasionally she takes more medicine than prescribed.

PE: Vital signs T 98.7 degrees oF, BP 100/70, HR 110, RR 14, and O2 Saturation 92%.

A physical exam reveals a somnolent female that arouses to a painful stimulus. The heart, lung, and extremity exam is normal. There are no focal neurologic deficits.

Workup

Laboratory studies, including a CBC, chemistry, and urinalysis, are normal except for a moderate elevation of the blood urea nitrogen and creatinine. A chest x-ray and pelvic film are negative for fracture. The ECG was normal. The drug screen is positive for opioids and cannabinoids.

The patient is given naloxone and becomes awake and conversant. She admits that she was sitting on the toilet urinating; the last thing she remembers is feeling faint. She indicates that she has difficulty sleeping and walking due to chronic hip pain, and she experiences severe pain with exercise in their home pool. She denies suicidal ideation. She admits to taking an extra pain pill and "smoking a joint" prior to the episode.

Checking E-FORCE reveals she has been on a three times a day dose of her oxycodone and acetaminophen for the last six weeks prescribed by her orthopedic surgeon.

Treatment

The patient is admitted to the hospital, and orthopedic surgery, pain management, pharmacy, physical therapy, and dietician are consulted. Subsequent workup by the interprofessional team concludes the incident was caused by an accidental overdose of her opioid medication combined with her comorbid conditions.

The family and husband were informed that due to age, diabetes mellitus, and kidney disease, the opioid analgesic that she is taking was cleared less efficiently. With the doubling of her dose, she developed an acute toxic encephalopathy. The family and patient have a limited understanding of the potential side effects of opioids in treating pain and a poor understanding of exercise and dieting for weight control.The interprofessional team recommends that the family continue opioids at the prescribed dose without any additional doses, rare NSAIDs for breakthrough pain, monitored physical therapy and exercise, a planned diet, temporary placement of a TENS unit, pain monitored by a pain specialist, and surgical intervention as soon as possible.

At discharge, a written treatment and management plan is presented to the family and patient for discussion and consent. The goals include relief of pain, increased exercise and weight loss, and surgical intervention as soon as possible.

The patient is scheduled for outpatient pain management, physical therapy, and weight management. Before discharge, the pharmacist counsels the family and patient regarding the safe use, dosage regulation, side effects, and proper disposal of opioid medication. An emergency naloxone kit is prescribed, and the family is educated on its use.

Follow-up

Three months after discharge, the patient successfully lost 40 pounds (18 kg) and was cleared for surgery. Following hip replacement, the patient's pain has dramatically diminished, and she has gradually tapered off her pain medications. She continues to maintain regular exercise and dieting until she is noticeably improved. She reports that she feels better, enjoys life, and is encouraged by her progress.