Prescription of Controlled Substances: Benefits and Risks

Continuing Education Activity

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 recognize the signs, symptoms, and treatment of acute and chronic pain as well as the signs and symptoms of patients misusing controlled substances. This activity assists members of the interprofessional team by helping develop an awareness of appropriate dosing, substance control, and recognizing patients that may be abusing these drugs for non-legitimate purposes.


  • 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.


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 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. 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 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 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 patient with chronic non-use disorder from the one who is 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]


  • 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 biologic, psychologic, 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 prescribing: 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 treatment.
  • Controlled substances: 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 comprise 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 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:

  • 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 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 the 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).

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 are those with 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 to be medically necessary and that 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 date of issue. 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 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, 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.

Pill 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 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. The use of these systems is gradually curbing "pill shopping."[6]


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 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 1% from internet

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. [7] Chronic pain syndromes have associations with many long-term conditions and diseases.


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


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:

  • 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.
  • If an individual engages in prescriber shopping, they 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


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.

  • 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 3-12 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


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. Now, the consensus is that overprescribing of opioid analgesics occurs, but it is still unclear in the literature where this takes place 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 the societal view on using prescription drugs is that it is normal, access may be easier and safer than obtaining illicit drugs, and since 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:

  • 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 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 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 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 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 as a result of 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 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, 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 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 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.

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 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 - 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 


The evaluation of 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. [8]

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

Treatment / Management

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 avoiding more medication than prescribed 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. [9]

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, for any treatment for more than a few days, the opioid prescription should include a treatment agreement or written informed consent. 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.

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 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.

Toxicity and Side 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. [10]

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


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.


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 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 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 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.

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, and pharmacists, etc., need to work together to assess and treat the patient's pain appropriately and to avoid addiction. The patient 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 make sure 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. [11][12]

Article Details

Article Author

Charles Preuss

Article Author

Arun Kalava

Article Editor:

Kevin King


2/17/2021 10:29:56 PM



Kaldy J, Controlled Substances Add New Layer to E-Prescribing. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists. 2016 Apr     [PubMed PMID: 27056356]


Manchikanti L,Kaye AM,Knezevic NN,McAnally H,Slavin K,Trescot AM,Blank S,Pampati V,Abdi S,Grider JS,Kaye AD,Manchikanti KN,Cordner H,Gharibo CG,Harned ME,Albers SL,Atluri S,Aydin SM,Bakshi S,Barkin RL,Benyamin RM,Boswell MV,Buenaventura RM,Calodney AK,Cedeno DL,Datta S,Deer TR,Fellows B,Galan V,Grami V,Hansen H,Helm Ii S,Justiz R,Koyyalagunta D,Malla Y,Navani A,Nouri KH,Pasupuleti R,Sehgal N,Silverman SM,Simopoulos TT,Singh V,Solanki DR,Staats PS,Vallejo R,Wargo BW,Watanabe A,Hirsch JA, Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain physician. 2017 Feb     [PubMed PMID: 28226332]


Jayawant SS,Balkrishnan R, The controversy surrounding OxyContin abuse: issues and solutions. Therapeutics and clinical risk management. 2005 Jun     [PubMed PMID: 18360547]


D'Aunno T,Park SE,Pollack HA, Evidence-based treatment for opioid use disorders: A national study of methadone dose levels, 2011-2017. Journal of substance abuse treatment. 2019 Jan     [PubMed PMID: 30466543]


Thomas CP,Ritter GA,Harris AHS,Garnick DW,Freedman KI,Herbert B, Applying American Society of Addiction Medicine Performance Measures in Commercial Health Insurance and Services Data. Journal of addiction medicine. 2018 Jul/Aug     [PubMed PMID: 29601307]


Rigg KK,March SJ,Inciardi JA, Prescription Drug Abuse & Diversion: Role of the Pain Clinic. Journal of drug issues. 2010     [PubMed PMID: 21278927]


Schug SA,Daly HCS,Stannard KJD, Pathophysiology of Pain . 2011     [PubMed PMID: 30485023]


Tenney L,McKenzie LM,Matus B,Mueller K,Newman LS, Effect of an opioid management program for Colorado workers' compensation providers on adherence to treatment guidelines for chronic pain. American journal of industrial medicine. 2019 Jan     [PubMed PMID: 30499587]


Copenhaver DJ,Karvelas NB,Fishman SM, Risk Management for Opioid Prescribing in the Treatment of Patients With Pain From Cancer or Terminal Illness: Inadvertent Oversight or Taboo? Anesthesia and analgesia. 2017 Nov     [PubMed PMID: 29049111]


Gomes T,Khuu W,Craiovan D,Martins D,Hunt J,Lee K,Tadrous M,Mamdani MM,Paterson JM,Juurlink DN, Comparing the contribution of prescribed opioids to opioid-related hospitalizations across Canada: A multi-jurisdictional cross-sectional study. Drug and alcohol dependence. 2018 Oct 1     [PubMed PMID: 30096638]


Clinton HA,Hunter AA,Logan SB,Lapidus GD, Evaluating opioid overdose using the National Violent Death Reporting System, 2016. Drug and alcohol dependence. 2019 Jan 1     [PubMed PMID: 30481691]


Rose AJ,McBain R,Schuler MS,LaRochelle MR,Ganz DA,Kilambi V,Stein BD,Bernson D,Chui KKH,Land T,Walley AY,Stopka TJ, Effect of Age on Opioid Prescribing, Overdose, and Mortality in Massachusetts, 2011 to 2015. Journal of the American Geriatrics Society. 2019 Jan     [PubMed PMID: 30471102]