One of the single most difficult challenges for any prescriber is to distinguish 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 as well as the signs and symptoms of patients using controlled substances for non-legitimate purposes.
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. The prescribing of 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 prescription of opioid analgesics peaked in 2011, since then both prescribing and overdose has 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.
Perhaps the biggest challenge of caring for patients with pain is that individuals have different levels of tolerance 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 not only appropriate patient assessment and treatment planning but also the possibility of use disorder, diversion, and potentially dangerous behavioral responses to controlled substances, e.g., opioid analgesics differ from pseudo-addiction 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 chronic non-use disorder pain patient from the one who is misusing their prescribed opioid. Lack of training and educational deficits often interferes with the appropriate prescription of opioid analgesic agents. To prevent misuse of controlled substances, providers that prescribe controlled substances should learn prescribing practices that minimize or prevent adverse consequences.
Five Characteristics of Addiction/Use Disorder (ASAM)
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 which guide their manufacture and distribution. Controlled substances have a high risk of resulting in an 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:
The Controlled Substance Act established five drug schedules and classified them to control their manufacture and distribution. Part of regulation requires providers that prescribe scheduled drugs and pharmacists that fill 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.
Of the five schedules, each has parameters based on their medical value, the risk of addiction, and ability to cause harm. The schedules range from schedule I (most potential for addiction and use disorder) to schedule V (least potential for addiction/use disorder).
Drug Use Disorder, Abuse, and Misuse
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 that results in personal, professional, or social problems. A patient that is abusing an opioid analgesic may no longer be appropriately interacting with their family, friends, or be able to perform their duties at work.
Misuse of a controlled substance refers to the use of 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 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 is 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, the potential for abuse and misuse will continue to increase.
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 they present with a different 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. Use of these systems is gradually curbing "pill shopping."
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 own 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 as well as illicit drugs imported or manufactured. In both instances, these drug sales and usage result in increased criminal activity as well as dangerous overdoses and death.
Methods of Obtaining Prescription Drugs
A review of multiple studies demonstrates a variety of means individuals obtain prescription drugs. The following summarizes the studies' findings.
Studies also reveal the source of the majority of these drugs was a single legal prescriber.
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. Chronic pain syndromes have associations with many long-term conditions and diseases.
COMMON CAUSES OF LEGITIMATE PAIN
Neurologic and Systemic Diseases that Cause Pain
Psychological Causes of Pain
Musculoskeletal Causes of Pain
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 use disorder to a controlled substance to control the pain increases. Risk factors for a use disorder to a pain medication include:
Factors that increase the risk of developing use disorder include:
Factors that decrease the risk of use disorder include:
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 per year, including those unable to work as a direct consequence of pain syndromes.
Pain is among the primary reasons individuals receive federal and private disability payment support.
The frequency of acute and chronic pain is believed to be increasing for several reasons:
FREQUENCY OF OPIOID RELATED CONCERNS
The Frequency of Opioid Prescribing and Consumption
Controlled Substance Use And Addiction/Use Disorder
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. Since the societal view on using prescription drugs is that it is normal, access may be easier and safer than obtaining illicit drugs and medications may be covered under insurance, more and more people chose 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:
Illicit drug use is growing. In the United States, since the clamping down 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 a substance such as a benzodiazepine or opioid. They are not aware of the danger if 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 of those patients prescribed opioids in an emergency setting, 5-10% are already consuming opioid medications from other prescribers. Many states have made this problem less prevalent by instituting statewide reporting of controlled substances prescriptions.
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 included an elevated heart rate, respiratory rate, and blood pressure. Pupillary dilation and diaphoresis may be evident.
Chronic pain usually does not involve sympathetic and may be associated with depression, fatigue, and loss of appetite and libido.
Typically occurs in response to acute tissue injury, results from activation of peripheral pain receptors and specific A-delta and C sensory nerve fibers (nociceptors).
Typically occurs in response to ongoing tissue injury 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 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 as a result of obstruction of a hollow organ is poorly localized, deep, and 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 painful 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 which 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 by endorphins such as enkephalin 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, antidepressants, and membrane stabilizing agents that interact with specific receptors and neurochemicals in the treatment of chronic pain.
Psychologic Factors Causing Pain
Psychogenic factors can modulate pain intensity. Emotion has a vital role in an individuals perception of pain. Patients in chronic pain have a high degree of psychologic 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 inappropriate 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 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 the perception of pain. Psychologic factors generate neural output that modulates neurotransmission along each of the pain pathways.
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 disorder.
Use disorder is a biological condition secondary to a variety of 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 use of a drug.
For prescribers, it may be difficult to distinguish legitimate pain from drug-seeking behaviors. 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
Symptoms of Pain
Pain Evaluation Questions
Signs and Symptoms of Drug Seeking 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
The evaluation of a patient needing opioid analgesics requires a complete history and physical, and laboratory and radiographic studies. Depending on the circumstances, consultation with psychiatry should be a consideration, addiction experts, physical, and occupational therapy.
The clinicians must have a complete understanding of the patients primary disease and any issues in regards to the evaluation of proper use, potential side effects, and effectiveness of opioid use for chronic pain.
Opioid analgesics should be prescribed for a limited period, typically several days to 3-4 weeks. The patient needs education in the risks and benefits of opioid treatment. Setting treatment goals should be done at the outset, including establishing the estimated time period, expected side effects, expected pain improvement, and avoidance of using more medication that prescribes without prior discussion with the provider. The plan for therapy should include the medication selected, starting dosage, measures to track pain relief, and associated therapies such as occupational or physical therapy.
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 respiration depression. The patient should make sure that only one prescriber should prescribe and monitor the opioid analgesic therapy. Further, patients should understand that all prescribers need to be aware of opioid dosing so that other agents, e.g., CNS depressants can be avoided which may interact and cause additional respiratory depression.
When prescribing opioid drugs, 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, for any treatment more than a few days, the opioid prescription should include a treatment agreement or written informed consent. Treatment agreements should include the following:
Prescribing practices should be stated, including:
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.
Examples of conditions that may require acute or chronic opioid analgesic use include:
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 that prescribes without prior discussion with the provider. The plan for treatment should include the medication selected, starting dosage, measures to track pain relief, and associated therapies such as occupational or physical therapy which can help decrease pain sensation.
The toxicities of prescribed opioid analgesics are avoidable if with appropriate daily dosing and opioid analgesics are not combined with other CNS depressants, e.g., ethanol, diazepam, and phenobarbital.
Constipation is a not uncommon side effect of opioid analgesics, and this is manageable with the careful use of laxatives. If laxative treatment is not effective, then drugs like methylnaltrexone can help relieve constipation and while maintaining pain control with the opioid analgesic, e.g., morphine.
Physicians should carefully evaluate and treat patients for short 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.
In the United States, two of the critical complications and public health concerns of opioid analgesics are overdoses and opioid use disorder.
Most clinicians should have the knowledge and ability to evaluate and treat patients for short acute pain syndromes and use opioid analgesics on a short-term basis. Those patients that require long-term pain control should probably receive a referral to a pain specialist.
All clinicians who regularly prescribe opioids should be familiar with opioid use disorder treatment options and be aware of local referral options. Seek referral to specialists when use disorder, pain, psychiatry, or mental health assistance as needed.
If a patient has a known use disorder, providers should refer the patient to both an addiction/use disorder and pain management professional. Unfortunately, clinicians that specialize in pain and use disorder 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 the prescription and management of an opioid analgesic prescription was medically necessary. Thorough medical records protect the prescriber and the patient.
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.
A common concern of patients is how effectively we treat their pain. The healthcare team, e.g., physicians, nurses, and pharmacists, etc. need to work collaboratively to assess and treat the patient's pain appropriately. The patient should always initiate therapy on the lowest dose possible, and then the dose and frequency gradually increased to achieve the desired effect, efficacy and tolerability. The prescriber should ensure that the patient clearly understands the need for regular monitoring of progress 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 risk of respiratory depression. The patient should make sure that only one healthcare provider prescribes and monitors their opioid analgesic therapy. Further, patients should understand that all healthcare providers they see are aware of any current opioid analgesic 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, for 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 to 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.
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