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Controlled Substance Prescribing

3 Contact Hours including 3 Advanced Pharmacology Hours
Florida & Texas Advanced Practice Requirement
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This peer reviewed course is applicable for the following professions:
Advanced Practice Registered Nurse (APRN), Certified Nurse Midwife, Certified Nurse Practitioner, Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Registered Nurse (RN), Registered Nurse Practitioner
This course will be updated or discontinued on or before Saturday, May 9, 2026

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.


≥ 92% of participants will understand controlled substance prescribing practices.


After completing this course, the participant will be able to meet the following objectives: 

  1. Define the risks of abuse and addiction associated with opioid medications.
  2. Describe the assessment and measurement of pain.
  3. State three principles for the safe and effective use of controlled substances.
  4. List three risk management tools used when considering prescribing controlled substances.
  5. Compare and contrast pharmacological and non-pharmacological methods to manage pain.
  6. Explain the use of opioids, benzodiazepines, barbiturates, and carisoprodol.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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Controlled Substance Prescribing
To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
  2. Reflect on practice impact by completing self-reflection, self-assessment and course evaluation.
    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Raymond Lengel (MSN, FNP-BC, RN)


Opioids manage pain but are associated with many risks, including abuse, diversion, and inappropriate use. A controlled substance is a drug, compound, preparation, mixture, or substance contained in Schedule I, II, III, IV, or V. This list is updated annually, and substances are classified into their schedules based on the substance's current medical use, abuse potential, and the likelihood of causing dependence.

Controlled substances are laced with risks. Understanding the dangers of controlled substances is critical for proper prescribing. The prescriber who understands the medications and prescribes them appropriately will provide better and safer care for their patients.

Prescription opioid abuse takes a heavy toll on the patient, healthcare provider, and society.  Abuse and misuse of controlled substances occur for multiple reasons, including self-medication, use for reward, diversion, and compulsive use. Opioid use has increased in recent times, leading to increased abuse and opioid overdoses. Proper screening lowers the risk of iatrogenic addiction. Unfortunately, no currently available screening method accurately predicts who is at high risk of abuse or misuse of opiates.

Misuse of prescribed medications describes potentially aberrant drug-taking behaviors. In 2016, 48.5 million individuals in the United States misused prescription drugs or used illicit drugs (Hoots et al., 2018). Sixty-six percent of the 630,000 drug overdose deaths were due to illegal or prescription opioids. The number of opioid overdoses in the emergency department increased by 30 percent from July 2016 to September 2017 (Hoots et al., 2018).

Healthcare providers tend to under-assess patients at risk for opioid-related aberrant behaviors.  One study showed that providers assessed the risk of misuse, abuse, or diversion at less than 2% when in reality, 10.4% of patients had prior illicit drug use, 23.4% had abnormal urine drug tests, almost 11% reported crushing or chewing opioids in the past, and 60% of patients self-reported abuse, misuse, or diversion (Setnik et al., 2017).

Prescribers' lack of training and inexperience can profoundly impact the misuse of medications. One study showed that resident physicians (compared to attending physicians) were more likely to prescribe opioids for more than three months (Strain et al., 2020). In addition, they were more likely to have their patients report that their prescriptions were lost or stolen. They were also more likely to have patients who exhibited substance misuse and were more likely to have their patients get opioids prescribed by a different prescriber in addition to them.

Prescribers receive little training in prescribing scheduled substances, screening for substance abuse, and referring patients who need treatment for substance abuse. Proper continuing education is one way to address this problem.

Substance Abuse

The National Institute of Drug Abuse (NIDA) reports findings on the cost of drug use. Data from NIDA suggests that illicit drug use is very costly to the United States, costing more than $740 billion each year in costs related to crime, lost work productivity, and health care. See Table 1, adapted from the NIDA (National Institute on Drug Abuse, 2017).

Table 1: Costs of Substance Use
SubstanceHealthcare Costs in DollarsOverall Cost in DollarsYear
Tobacco168 billion300 billion2010
Alcohol27 billion249 billion2010
Illicit Drugs11 billion193 billion2007
Prescription Opioids26 billion78.5 billion2013

Substance abuse issues are a genuine concern in the management of pain. Inappropriate prescriptions of pain medications have the potential to increase patients' chances of medication abuse. Below are some statistics regarding the current state of substance abuse:

  • According to the Center for Disease Control and Prevention (CDC), 41 people die each day in the United States from an overdose of prescription painkillers (Center for Disease Control, 2020).
  • Overdoses from synthetic opioids increased from 3.1 per 100,000 people in 2015 to 6.2 people per 100,000 people in 2016 (Hedegaard et al., 2017).
  • Between 1999 and 2015, drug overdose deaths have tripled (Black et al., 2020).
  • About 53 percent of people who have ever tried heroin develop heroin abuse or dependence (Strain et al., 2020).


Prescription drug misuse involves using prescription medication with a method or intent inconsistent with how it was prescribed. Misuse includes using medicine to get high, selling or sharing it with others (diversion), overuse, having multiple prescribers, and concurrent use of alcohol or other illicit substances. Misuse is a necessary but not solely a sufficient criterion for a substance use disorder (McKay, 2020).

Susceptible individuals are at risk of misusing medications that stimulate the brain's reward center, including opioid analgesics, stimulants, benzodiazepines, or tranquilizers. Medically or socially inappropriate drug use defines drug abuse. Controlled substances may lead to dependence, either physical or psychological. Physical dependence transpires when withdrawal symptoms include anxiety, tachycardia, hypertension, diaphoresis, a volatile mood, or dysphoria after the substance's rapid discontinuation (McKay, 2020).

Psychological dependence is the perceived need for the substance (McKay, 2020). It makes the person feel as though they cannot function if they do not have the substance. Psychological dependence often kicks in after physical dependence wears off. It typically lasts much longer than physical dependence and often is a substantial contributing factor to relapse.

Addiction is psychological dependence and extreme behavior patterns associated with the drug (McKay, 2020). At this point, there is typically a loss of control regarding drug use and continued drug use despite severe medical and social consequences. Tolerance, increasing doses of the medication needed to produce an equivalent effect, typically occurs when addiction is present. Physical dependence can occur without addiction. Individuals who take chronic pain medication may be dependent on the medication but not addicted (McKay, 2020).

Addiction is a primary concern in those taking opioids. When prescribing opioids, it is essential to determine who is likely to participate in aberrant drug-related behaviors. Misuse may occur in those with major depression, psychotropic medication use, younger age, or family or personal history of drug or alcohol misuse. The prescriber and a specialist should co-manage the patient.

Aberrant behaviors may include abuse, misuse, or addiction. Examples of aberrant drug-related behaviors include (McKay 2020):

  • Requests for early refills
  • Not taking medications as prescribed
  • Failure to keep appointments
  • Visits in distress
  • Frequent reports of lost medication
  • Using multiple prescribers
  • Positive urine drug test for illicit substances
  • Altering prescriptions
  • Resistance to referrals
  • Resistance to providing prior medical records
  • Resistance to change in therapy
  • Increasing the dose without telling the prescriber
  • Requests for specific drugs


Addiction is a chronic condition that tends to relapse. Traditionally, treatment involved managing withdrawal signs and symptoms and then limited outpatient treatment, with the actual duration of outpatient treatment being less than 30 days (McKay, 2020). Research indicates that between 40 and 60 percent of individuals treated for drug or alcohol dependence go back to regular use within 12 months (McKay, 2020).

Management includes continual assessment of the patient's risk of relapse, and treatment intensity is modified based on individual risk. Patients are taught self-management skills, utilize community support services, work with mental health providers, and take prescribed medications to manage drug addiction's physiological effects (Saxon & Strain, 2019).

Addiction leads to functional and structural alterations in the brain. Brain volume loss is seen with cocaine use, opiate use, alcohol dependence, and polysubstance abuse (McKay, 2020). In addition, dopamine and endorphins are changed in those who chronically use drugs and alcohol.   Early life addiction may lead to difficulty obtaining practical life skills resulting in chronic functional deficits (McKay, 2020).

Addiction treatment has shifted to a chronic care model working with patients over time instead of short-term interventions during an acute crisis with addiction. Patients are taught skills to encourage self-management of addiction. Treatment involves linking patients to community resources.

Some addicted individuals need more care than others. Individuals who have been in recovery for extended periods may only require brief, sporadic assessments to manage their disease.  Those who are at high risk of relapse may need long-term, intensive, structured care.

Pain Assessment: When and How Should Pain Intensity be Assessed?

According to the Joint Commission Statement on Pain: "The hospital assesses and manages the patient's pain." The current Joint Commission standard requires that facilities implement pain assessment policies, treat pain, and carry out staff education to ensure the implementation of proper policies (Joint Commission, 2017).

Regardless of the patient setting, the intensity of pain should be assessed and documented (Joint Commission, 2017):

  1. During the initial evaluation of the patient.
  2. After any known pain-producing procedure.
  3. With each new report of pain.
  4. At suitable intervals after pharmacologic (45-60 minutes after an oral intervention; 15-30 minutes after parenteral intervention) or non-pharmacologic intervention to evaluate the current pain treatment plan.

Pain threshold refers to the minimal level at which an individual senses pain as a harmful stimulus. It is the level at which the patient first states that what they are feeling is painful and varies significantly from patient to patient.

Pain tolerance refers to the degree of pain a person can tolerate before it becomes unbearable for them. Pain tolerance differs from patient to patient and varies for the same individual depending on numerous factors, including time, setting, and stimulus. Healthcare providers must resist the temptation to compare patients' pain thresholds and tolerance, especially those with similar procedures.

Measuring the severity of pain is often done on scales. Pain scales compare the intensity of the patient's pain at different time points, not compare one person's pain to another. The use of pain scales assists the healthcare provider in determining the effectiveness of pain treatment.

It is essential to consider which type of scale would work best for the individual patient. The best scales are brief, valid, require minimal training, and use behavioral and descriptive pain measures. Patient education regarding pain assessment is also important; for example, before a surgical procedure, the nurse needs to discuss how their pain will be assessed after the surgery and demonstrate how the Numbering Rating Scale and the Wong-Baker FACES Pain Rating Scale work. After explaining each to the patient, allow the patient to choose which scale will work better.

Numerical Rating Scale (NRS)

A "0 to 10" numerical scale is the most widely used measure to assess pain intensity. When using the Numerical Rating Scale (NRS), patients rate their pain from 0 to 10, with "0" equaling no pain and "10" equals the worst possible pain one can imagine. This numeric pain scale has become widely used, but an unexpected result is prescribing specific doses of opioid pain medication centered exclusively on pain intensity (Joint Commission, 2017). Prescribing pain medication in this way is a practice that is commonly referred to as "Dosing to Numbers" and has become an issue for several reasons: pain ratings are an utterly subjective finding, pain cannot be measured objectively, and pain ratings are frequently not a repeatable finding even for the same patient.

No research indicates that a given dose of opioids will produce pain relief for a specific pain intensity level in all patients. In a position paper released by the American Society of Pain Management Nursing (ASPMN), the organization states that "prescribing doses of opioids based solely on a patient's pain intensity should be prohibited." The ASPMN believes that this practice does not consider other facets of pain management assessment, and basing opioid administration entirely on a numeric value on a pain intensity scale results in poor pain control. The ASPMN advocates that "safe and effective opioid dosing is dependent on the careful assessment of multiple objective measures," and they include in these findings the following (American Chronic Pain Association [ACPA], 2020):

  • Age of the patient
  • Other existing healthcare conditions
  • Level of sedation
  • Patient's respiratory status
  • Other sedating medications being used
  • Patient's previous response to opioid medication
  • A subjective measure of pain intensity

Pain Maps

Another scale (see Image 1) allows patients to rate their pain as "no pain, mild pain, moderate pain, severe pain, or unbearable pain."

Image 1: Pain Scale

pain map scale

Pain maps can be used for those who have a difficult time speaking. In a pain map, there is a front and rear view of the body on a piece of paper, and the patient draws on the location of the pain and rates the severity of the pain.

Since we have no instrument to objectively measure pain intensity in the same way that a sphygmomanometer measures blood pressure, the only valid measure of pain is the patient's self-report (a subjective measure). Sometimes, healthcare providers may believe they are the best judges of a person's pain; however, many studies demonstrate that healthcare providers either over or underestimate a patient's pain.

Wong-Baker FACES Pain Rating Scale

Patients who are NOT cognitively impaired but cannot respond verbally can rate their pain numerically using face scales with happy faces representing no pain and progressively sadder faces representing increasing pain intensity. The patient chooses the face that best depicts how they are feeling. Being unable to report pain reliably makes a patient vulnerable to underappreciating pain and the possibility of under or overtreatment of pain. Nurses play an essential role in ensuring that pain is accurately assessed and treated in these vulnerable populations.

Image 2: Wong-Baker FACES Pain Rating Scale

pain chart with faces going from happy to sad in expression

Pain Assessment

Besides current pain intensity, the complete pain assessment includes the following:
  1. Location of pain. Where does the pain start, and does it spread to other parts of the body?
  2. Pain intensity for the worst pain, the best pain gets, and the acceptable level of pain. Satisfactory pain relief is a level of pain that may be noticeable but not bothersome.
  3. Character or quality of pain. The words used by the patient to describe pain may enhance the understanding of the etiology of the pain and provide usefulness in selecting interventions to manage it. For example, somatic (musculoskeletal) pain is usually localized and described as dull, achy, and sore. Visceral pain is usually poorly localized and described as cramping or squeezing pain. Descriptors of burning, shooting, or knife-like are indicative of neuropathic (nerve) pain. Refer to Table 2 for more information on pain types, description, etiology, and treatment.
  4. Onset, duration, variations, and pattern (Is the pain better or worse at certain times, certain hours?).
  5. Alleviating factors – What makes the pain better?
  6. Aggravating factors – What makes the pain worse?
  7. Impact of pain on quality of life and daily functioning. How does the pain affect sleeping, relationships with others, mood, emotions, and concentration?
Table 2: Pain Assessment
Pain TypeDescriptionEtiologyTreatment
  • Burning
  • Shooting
  • Tingling
  • Numbness
  • Radiating
  • Nerve involvement
  • Tumor
  • Post-herpetic neuralgia
  • Diabetic neuropathy
  • Post-stroke pain
  • Antidepressants
  • Anticonvulsants
  • Local anesthetics
  • Opioids
Visceral (Poorly localized)
  • Squeezing
  • Cramping
  • Pressure
  • Distention
  • Deep
  • Tumors occupying the:
    • liver
    • pancreas
    • spleen
  • Abdominal or thoracic surgery
  • Ascites
  • Non-opioids
  • Acetaminophen
Somatic (Well-localized)
  • Dull
  • Achy
  • Throbbing
  • Sore
  • Bone metastases
  • Musculoskeletal injury
  • Mucositis
  • Skin lesions
  • Co-analgesics
  • Corticosteroids
  • Local anesthetics
  • Bisphosphonates
  • Radioisotopes

It is also essential to document the impact pain has on quality of life. Key questions to ask include:

  • Does pain affect sleep?
  • Does the pain lead to mood alterations?
  • Does the pain lead to reduced energy?
  • Does the pain reduce the patient's ability to participate in activities and socialize?
  • Does the pain affect relationships?
  • Does the pain limit or affect activity or exercise?
  • Can the patient participate in daily living activities such as bathing, dressing, feeding, toileting, or brushing their teeth?
  • Does the pain impact instrumental activities of daily living (IADL), such as using the telephone, doing the laundry, handling medications, or managing the finances?  IADLs are less critical in the nursing home setting as many are impaired at baseline, so there was nursing home placement.

Review of Medical History

Understanding how pain was treated in the past for the patient will help the clinician treat the current pain. A review of past medical records helps the pain management team evaluate the condition (ACPA, 2020). Reviewing all previous history, diagnostic testing, treatment options, and the efficacy of those options helps the team make an accurate diagnosis and manage pain appropriately. Certain treatment modalities, including specific medications, are often more effective in one individual when compared to another based on individual genetic variations.

Chronic disease may have a substantial impact on the management of pain (ACPA, 2020). Chronic kidney disease, for example, reduces medication excretion. The use of non-steroidal anti-inflammatory medications contributes to kidney failure in patients with chronic kidney disease. Having a complete understanding of all medical and surgical conditions helps assure proper pain management.

A mental health evaluation helps the clinician understand the best way to manage pain. Mood or cognitive disorders affect pain management (ACPA, 2020). Chronic pain cannot be adequately managed in those with unidentified and untreated mental illness. A history of drug abuse is essential to ascertain, which could profoundly affect chronic pain treatment. Personal characteristics may have a substantial effect on pain management. Factors that influence pain include race, age, culture, religion, sex, or language.

A review of the patient's perception of the pain is essential (ACPA, 2020):

  • Why does the patient believe they have persistent pain?
  • Does the patient feel there was adequate workup done on their condition?
  • What does the patient expect out of treatment?
  • What are the patient's goals? 

Psychological factors that contribute to the pain should be assessed to help assess the patient's expectations. Patients need to have realistic expectations about pain management.

Physical Exam

A complete physical exam is an essential part of the management of pain (ACPA, 2020). It is vital to have a baseline examination so subsequent evaluations will allow the healthcare team to determine pain management and functional capacity progress.

The physical exam should include a detailed neurological exam, including the patient's ability to ambulate. Observing hygiene, posture, dress, and appearance is essential as well. Those with severe pain often have poor hygiene, unkempt dress, and appear to be in pain. Observe for any splinting, which may suggest a painful part of the body.

Assessing skin and joints for redness, swelling, or deformities helps determine the location and etiology of pain. Perform an abdominal exam for any tenderness or distention. Also, checking joints for a full range of motion is essential for the physical exam in chronic pain. The exam should include an evaluation of functional capacity, strength, endurance, and any pain-related limitations (ACPA, 2020).

Ongoing monitoring of the efficacy and effectiveness of the implemented plan is essential.  Utilizing similar assessment tools, the healthcare provider can document the effectiveness of the pain management plan on the patient, including improved quality of life.

Diagnostic Tests

Diagnostic testing helps evaluate painful conditions. It is essential to realize that an abnormal diagnostic test does not confirm the source of the pain. Blood tests can be helpful in some conditions to determine or monitor specific causes of pain. For example, an elevated C-reactive protein or an erythrocyte sedimentation rate may be seen in those with polymyalgia rheumatica, infection, or rheumatoid arthritis (which are all conditions that may cause pain).

Imaging may be necessary for some situations of chronic pain. X-rays, computed tomography, and magnetic resonance imaging can help define the etiology of the pain (Strain et al., 2020). Use caution when imaging, as many abnormalities may be seen in imaging tests that are not the pain source.

An electromyogram (EMG) or nerve conduction studies assess the cause of pain (Strain et al., 2020). The EMG measures the muscle's electrical activity and can help find damaged muscle, nerves, or neuromuscular abnormalities such as herniated discs or myasthenia gravis. The nerve conduction study measures the nerves' ability to send electrical signals and helps diagnose carpal tunnel syndrome or other neuropathies.


In recent times, opioid therapy has become more commonly used. In the past, it was only used for severe acute pain and cancer pain (Black et al., 2020). A position paper from the American Academy of Neurology suggested evidence for good short-term pain relief with opioids. However, no good evidence exists showing continued pain relief or improved function with opioids for extended periods without sustaining a severe risk of dependence, overdose, or addiction.

Opioids function by activating opioid receptors that are located in the spinal cord and the brain. Most of the pain relief related to opioids is their actions on the periaqueductal gray (PAG) cells and the descending pain pathways. Opioid receptors are molecules located on the surface of cells; opioid substances attach themselves to them and release their effects.

There are three different opioid receptors found in the brain: Mu, Kappa, and Delta receptors (Strain et al., 2020). Mu and Kappa receptors are also found in the spinal cord and mediate pain transmission from the brain's peripheral nervous system. A primary pain receptor in opioid abuse and treatment is the Mu receptor. When opioids activate Mu receptors, the most significant potential for pain relief and addiction is initiated. However, Kappa and Delta receptors also play a role in opioid addiction.

Controlled Substance Act

The Controlled Substance Act divided drugs and other substances into five schedules, updated annually here:

  • Schedule I controlled substances have no accepted medical use in the United States; they include heroin and lysergic acid diethylamide (LSD).
  • Schedule II and IIN substances may potentially be abused and may lead to severe physical or psychological dependence.
  • Schedule II narcotics include oxycodone (OxyContin, Percocet), hydrocodone (Vicodin, Zohydro ER), Fentanyl (Sublimaze, Duragesic), methadone (Dolophine), hydromorphone (Dilaudid), morphine, opium, and codeine.
  • Schedule III or IIIN substances have less abuse potential than those substances that are Schedule I or II. They are at high risk for psychological dependence and low to moderate risk of physical dependence. Examples of medications in this class include buprenorphine (Suboxone) and products with less than 90 milligrams of codeine per dosage unit, such as Tylenol with codeine. Schedule IIIN includes anabolic steroids such as Depo-Testosterone and ketamine.
  • Schedule IV controlled substances have a lower potential for abuse when compared to Schedule III controlled substances. Examples of this class include benzodiazepines, midazolam (Versed), tramadol (Ultram), and carisoprodol (Soma).
  • Schedule V controlled substances have a low abuse potential relative to Schedule IV and include cough preparations containing less than 200 milligrams of codeine per 100 milliliters or 100 grams, such as Robitussin AC.

Most controlled substances alter mood, feeling, or thought due to their effect on the central nervous system. Medications likely to produce euphoria are more likely to be abused, but medications may be abused to aid in sleep, reduce pain, reduce anxiety, reduce depression, and improve energy.

Pain Management

The goals of pain management are not necessarily complete pain relief. They may include reducing pain, improved quality of life, improved physical and psychological functioning, improved ability to work, improved ability to function in society, and reduced healthcare utilization (Strain et al., 2020).

A pain management plan is more than just a prescription for pain medication (Strain et al., 2020). In addition to pharmacotherapy, it should include psychological and physical modalities to manage pain.  It should be modified when interventions are not effective. Successful treatment of chronic pain requires an interdisciplinary healthcare team's input and a holistic approach to care to improve the patient's overall quality of life. One of our most essential roles is listening to our patients, which is especially important for patients with chronic pain. These patients often live with intense fear, anxiety, uncertainty about the future, and frequently social isolation and loneliness. The opportunity to tell one's story to someone who is consciously listening is therapeutic in itself.

Educate the patient regarding the plan. Education should include medications prescribed, other treatment options, and methods to contact the pain management team.

When developing a treatment plan, there are many considerations. Consider the type of pain and its effect on lifestyle, including psychological, social, and biological components of life.

Many factors affect the success of the treatment plan (Strain et al., 2020). Issues related to the patient, such as their ability to understand and apply the management plan, will help determine its success. The patient's willingness to implement the whole plan can profoundly affect the plan's success. If a patient is willing to take a pill but is unwilling to work on non-pharmacologic interventions (such as physical therapy or weight loss), the plan will lose its effectiveness.

Referral to a pain management specialist may be indicated for those who have debilitating symptoms, need increased doses of pain medications, are non-responsive to treatments, or have symptoms at multiple sites (Strain et al., 2020). In addition, any APRN who does not provide long-term pain management to patients with intractable pain should refer the patient to a provider whose primary practice is to manage the pain.

Caregiver or healthcare provider issues often affect the pain management plan (Strain et al., 2020). Many caregivers and healthcare providers do not accurately comprehend the patient's pain and may hold false beliefs regarding pain management. Caregivers and healthcare providers may be inhibited by fear of side effects from medications or drug addiction concerns; therefore, they may withhold medication from pain patients. Also, caregivers, healthcare providers, and patients may have conflicting goals.

Prescribe controlled substances for a legitimate medical purpose while carefully considering the patient's safety, therapy goals, and efficacy. Not only should the treatment of pain include pharmacotherapy but also physical and psychological therapies. Many caregivers lack knowledge and understanding of non-pharmacological pain treatments and cannot provide patients with the full scope of available pain therapies.

Chronic Pain Guidelines

Clinical practice guidelines for outpatient management of chronic non-malignant pain discusses how to treat chronic pain to improve function and quality of life. The guidelines specifically discuss the use of opioid medications.

Key Principles of Prescribing

Key principles outlined by the guidelines include (Tennessee Department of Health, 2020):

  • A previous prescription for opioids is not a good reason to continue the prescription
  • Implement non-opioid treatments before opioids
  • All pregnant women should take a urine drug test
  • Discuss a birth control plan when opioids are started in a female of childbearing age to avoid unintended pregnancy
  • Document a complete evaluation supporting the use of opioids before writing a prescription
  • Do not prescribe controlled substances to manage pain through telemedicine

Before starting opioid therapy, multiple steps should occur. The provider should (Tennessee Department of Health, 2020):

  • Complete a full history, including the impact pain has on patient functioning
  • Assess for co-morbid medical and mental health conditions
  • Perform a comprehensive physical exam
  • Evaluate for a history of substance abuse disorder
  • Review of prior medical records
  • Evaluate females of childbearing age for pregnancy and establish an appropriate diagnosis to justify opioid therapy

If a woman gets pregnant when on opioid therapy, she must inform her healthcare provider. If opioids are continued during pregnancy, educate the pregnant patient on the risks versus the benefits and the risk of stopping opioids during pregnancy and obtain informed consent that they understand. Risks of stopping medication without proper supervision include preterm delivery, relapse, fetal distress, intrauterine withdrawal, and fetal death. Pregnant women who continue therapy should be managed by an obstetrician, a pain management specialist, or a medical replacement treatment program (Tennessee Department of Health, 2020).

Before prescribing opioids, an assessment for abuse potential should occur. Common tools used to assess risk include

  • The Brief Risk Interview (BRI)
  • The DIRE Score: Diagnosis, Intractability, Risk, Efficacy score
  • The Opioid Risk Tool (ORT)
  • The Pain Medication Questionnaire (PMQ)
  • The Screener and Opioid Assessment for Patients with Pain (SOAPP).

In addition, it is essential to obtain a urine drug test to check for other controlled substances or illegal substances and evaluate previous prescription patterns utilizing the Substance Monitoring Database (Tennessee Department of Health, 2020).

The clinician and patient should establish goals for treatment. Goals focus on improvement in function and reducing pain, not eliminating pain. The three-item PEG assessment scale monitors response to treatment. The PEG tool assesses (Tennessee Department of Health, 2020):

  • The average Pain over the last week
  • How much pain interferes with the Enjoyment of life
  • And how much the pain interferes with General activity

Non-pharmacological Therapy

Numerous non-pharmacologic therapies manage pain. These may include a combination of physical and psychological techniques. Some methods used other than medications include physical therapy, exercise, massage, ultrasound therapy, heat/cold application, chiropractic manipulation, psychotherapy, biofeedback, relaxation therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS), music therapy, injections, neuromodulation, spinal cord stimulation, deep brain stimulation, and radiofrequency ablation of nerve tissue (National Institute of Health [NIH], 2018).

For those with pain, a trial of physical therapy or occupational therapy can be helpful. With the help of a physical therapist, exercises targeting a specific type of pathology can help manage pain. Occupational therapists can help recommend devices that can assist in enhancing activities of daily living.

There is a tendency not to move with chronic pain, which leads to deconditioning and further incapacity—deconditioning results in more significant pain with any form of movement. Maintaining muscle mass prevents this downward spiral. The more an individual participates in exercise, the less probability of developing back pain. For those who have lower back pain, physical activity improves overall health significantly. Exercise, especially in water, is beneficial for patients with arthritis pain, and aerobic exercise has effectively decreased pain connected with fibromyalgia (NIH, 2018).

Yoga and Pilates have also become popular alternative treatments, especially for back pain (NIH, 2018). Tai' Chi, a Chinese practice involving slow, gentle movements, deep breathing, and relaxation, has positive effects on pain relief for several conditions, including fibromyalgia, arthritis, and low back pain. However, some yoga poses can be a potential cause of injury, especially those that involve overstretching of the neck.

Massage is soothing and relaxing, both physically and mentally. Massage may decrease pain by relaxing muscle tension and increasing capillary circulation, thereby improving general circulation.

A vibration is a form of electric massage. When vibration is applied lightly, it may have a soothing effect similar to massage. Vibration used with moderate pressure may relieve pain by causing numbness, paresthesia, and anesthesia of the area stimulated.

Heat and cold therapies can assist in managing pain (NIH, 2018). Heat reduces inflammation and promotes relaxation. It can be in the form of hot tub baths, heating pads, or heat packs. Cold is often more effective in relieving pain than heat. The application of cold reduces muscle spasms secondary to underlying skeletal muscle pain, joint pathology, or nerve root irritation. Cold application methods include ice massage, ice bags, and gel packs. Alternating heat and cold may be more effective than using either one alone.

Multiple psychological techniques can aid in reducing pain. The basis for using these methods is that thought influences feelings, and if thought (and behaviors) can be changed, so can feelings and even sensations, such as pain. Cognitive-behavioral methods require the patient's active participation.

Cognitive-behavioral therapy (CBT) is an effective coping skill for those with chronic pain (NIH, 2018). CBT emphasizes the present moment, where the individual becomes aware of their thoughts, feelings, and behaviors, and may include journaling these perceptions. CBT helps decrease the emotional distress associated with chronic pain by focusing on perceiving pain and adjusting to it. CBT decreases pain in chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and back pain. It also helps prevent headaches.

Relaxation is a state of relative freedom from anxiety and skeletal muscle tension, quieting or calming the mind and muscles. Relaxation is a learned technique but can be learned quickly in a motivated patient.

Imagery/visualization involves mentally creating a picture by using one's imagination. This mental picture may focus on a person, a place of enjoyment, a past event, or anything that brings pleasure. An occupied mind does not focus on the pain.

Distraction from pain is the focusing of attention on stimuli other than the pain sensation (NIH, 2018). The stimuli focused upon can be auditory, visual, or tactile-kinesthetic (hearing, seeing, touching, and moving). By concentrating on stimuli other than pain, the pain moves to the periphery of awareness. Distraction does not make the pain go away, nor does the effectiveness of distraction indicate the absence of pain. Music and humor are good means of distraction.

Transcutaneous Electrical Nerve Stimulation (TENS) provides low-voltage electricity to the body via electrodes placed on the skin. TENS may help with acute or chronic pain. Electrical stimulation of sensory nerves helps block pain signals going to the brain. TENS is contraindicated in patients with pacemakers, electrical implants, cardiac arrhythmias, circulation problems, and pregnancy.

Biofeedback is a technique to harness the mind's power to make the patient more aware of the body's sensations. Its exact mechanism is unclear, but it promotes relaxation and helps reduce pain (NIH, 2018).

Acupuncture is a neurostimulation technique that treats pain by inserting small, solid needles into the skin at varying depths. Various theories exist to explain how acupuncture works. The Chinese theory of acupuncture is that it allows the release of blocked energy in the body. In Chinese medicine, this energy source is known as Qi, and its ability to flow freely through the body is related to overall well-being (NIH, 2018).

Music therapy treats pain. Music therapy is the clinical and evidence-based use of music interventions to accomplish individualized goals within a credentialed professional's therapeutic relationship. This individual has to complete an approved music therapy program. Research in music therapy supports its effectiveness in a wide variety of healthcare and educational settings (NIH, 2018).

Music therapists use music to facilitate changes that are non-musical. Individuals doing music therapy listen to music created under the guidance of a specially educated and certified professional in music therapy.

The theory of music therapy's effect on chronic pain deals with how pain signals travel through the body. When the brain senses injury to the body, pain signals begin in the somatosensory cortex and the hypothalamus and work their way through the "pain pathway," ultimately sending signals that provide pain relief. Some signals stimulate the release of neurotransmitters such as endorphins, dynorphins, and enkephalins. Music helps in pain reduction by activating these sensory pathways. Like relaxation and guided imagery, music can strengthen the brain's right side, which controls the body's healing processes.

Different surgical interventions or procedures assist in the pain management plan. Procedures include injections, spinal cord stimulation, deep brain stimulation, neural ablative techniques, and surgical interventions. These are potential options for those for whom other methods have not controlled the pain (NIH, 2018).

Teaching Coping Skills

Pain has two parts. First of all, there is the perception of pain, which is related to the strength and characteristics of the pain, and secondly, there is the effect the pain has on the individual.

What is its emotional impact, and how is it impacting their quality of life? In a pain assessment, healthcare providers measure the strength or intensity of the pain, which may not reflect how the pain affects their lives. How pain affects an individual is intimately associated with the patient's ability to cope with the pain.

Coping can be defined as what an individual thinks and does in a situation that causes stress. It is greatly affected by the resources that are available to the person to manage the event.  Coping is a crucial part of pain management, especially for those with chronic pain. Healthcare providers need to be aware of the necessity to assess the patient's coping patterns as they relate to pain and to be able to discuss necessary coping skills with them.

Catastrophizing is the opposite of coping and is the belief that a situation will continue to worsen, and it is an essential predictor of pain and adjustment, especially in chronic pain. However, recent research has shown an important link between acute pain and pain catastrophizing (Block et al., 2017). The individual experiences heightened levels of worry and fear that have intensified the person's amount of pain.  Instead of problem-solving, the individual tends to turn away and feel hopeless about their situation. Catastrophizing needs to be something that nurses are watchful of when assessing a patient's pain by listening carefully to how the patient describes their pain and how they perceive its effect on their life now and in the future.

Pharmacologic Interventions

Undertreatment of chronic pain remains a persistent problem, with an estimated of approximately 30% of those who suffer from chronic pain receiving less than adequate treatment (American Chronic Pain Association [ACPA], 2020).

Pain medication may be administered on an as-needed basis for episodic pain or given routinely for chronic pain. The use of routine, around-the-clock medication sustains a steady state in the blood and offers better pain relief for those with persistent pain (ACPA, 2020). Consider side effects when deciding which medication to use.

Medication classes include non-opioid analgesic agents, antidepressants, muscle relaxants, antiepileptic medications, topical agents, and opioids. Some get adequate relief from one medication, but some get better pain relief from a combination of medications that work on different pathways. Unfortunately, research is sparse on combination medication in the management of pain (ACPA, 2020).

Considering all co-morbidities is an essential step in pain management (ACPA, 2020). For example, when a patient suffers from chronic pain and depression, some medications may help effectively manage both conditions (for instance, duloxetine treats chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain in addition to depression). It is also essential to establish the pain syndrome's pathophysiology, evaluate the medication list, and consider the medications' side effects (ACPA, 2020).

The clinician should distinguish between neuropathic and nociceptive pain (ACPA, 2020). Establish the etiology of neuropathic pain and manage the underlying problem if the etiology is reversible. For example, if a medication (e.g., metronidazole, nitrofurantoin, isoniazid, or many cancer agents) is the cause of the neuropathy, stop that medication (if possible).

Medications used in treating neuropathic pain include gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants, serotonin-norepinephrine uptake inhibitors (SNRIs), the lidocaine patch, and narcotic analgesics (ACPA, 2020).

Nociceptive pain is treated with non-narcotic and opioid analgesia (ACPA, 2020). Common causes of nociceptive pain include arthritis and chronic low back pain.


Acetaminophen is used as a first-line agent in the management of nociceptive pain.

Acetaminophen has become a chief cause of acute liver failure. According to government statistics, close to 30,000 hospital admissions are annually associated with acetaminophen overdose (ACPA, 2020). Warn patients that alcohol and acetaminophen are hazardous mixtures and should not be combined.  In January 2011, the Food and Drug Administration (FDA) requested drug manufacturers to limit acetaminophen in combined products to 325 milligrams per dose. The FDA also required that labels carry a 'black-box' warning, highlighting that acetaminophen can result in severe liver damage (ACPA, 2020).

Acetaminophen is not an anti-inflammatory agent but is a very common over-the-counter medication used to manage pain. Acetaminophen is commonly administered with opioid medications to reduce the opioid medication needed to manage the pain (ACPA, 2020).

Acetaminophen is dosed 325 to 650 mg every four hours or 500-1000 mg every 6 hours, not to exceed 3000 to 4000 mg a day. In the pediatric population, acetaminophen is dosed at 10-15 mg/kg/dose every 4-6 hours with a maximum of 75 mg/kg/day, but no more than 4000 mg a day.  Reduce the dose in those with hepatic insufficiency or alcohol abuse. Absolute contraindication to acetaminophen is liver failure, while relative contraindications include chronic alcohol abuse or hepatic insufficiency. Those who are on a statin cholesterol medication may need a lower dose of acetaminophen (ACPA, 2020).

Before going to stronger pain medication, clinicians must ensure proper acetaminophen dosing. The use of up to 1000 mg per dose (in adults) may be necessary to provide relief.

Non-Steroidal Anti-Inflammatories

Non-steroidal anti-inflammatory drugs (NSAIDs) are used as alternative options to acetaminophen and are indicated for mild to moderate pain and some severe pain. Like acetaminophen, they act synergistically with opioids (ACPA, 2020).

These anti-inflammatory agents treat arthritis, strains, sprains, bursitis, and tendonitis.

Frequently used NSAIDs are (ACPA, 2020):

  • Acetylsalicylic acid (Aspirin®, which is the oldest known NSAID)
  • Ibuprofen (Advil®, Motrin®)
  • Naproxen (Aleve®)
  • Diclofenac (Voltaren®)

NSAIDs inhibit the production of the enzymes cyclooxygenase 2 (COX-2) and cyclooxygenase 1 (COX-1), which are involved in the synthesis of prostaglandins that mediate inflammatory responses and cause pain (ACPA, 2020). COX-1 is involved in protecting the stomach lining from the damaging effects of acid, and one of the most frequently cited side effects of NSAIDs is stomach bleeding. Do not use aspirin in children under 17 because of the danger of Reye's Syndrome.

Compared to acetaminophen, NSAIDs are associated with more side effects and are more problematic, especially in older adults. In older adults, the American Geriatric Society guidelines recommend that persistent pain due to osteoarthritis not be primarily managed with non-steroidal anti-inflammatory agents (Ali et al., 2018). The use of topical NSAIDs is a good option for those with localized pain.

Absolute contraindications to NSAIDs include an active peptic ulcer, chronic kidney disease, or heart failure. Relative contraindications include a history of peptic ulcer disease, Helicobacter pylori infection, hypertension, or concomitant use of selective serotonin receptor inhibitors or corticosteroids.

NSAIDs' side effects include renal insults, adverse cardiovascular effects, headaches, constipation, and mental status changes. Gastrointestinal effects may include gastric ulceration and dyspepsia. Taking the medication with food or antacids may reduce the risk of dyspepsia.  Those at high risk of gastric ulceration – older age, taking corticosteroids, bleeding problems, or a history of gastric ulceration – should not use NSAIDs. For those with compromised gastrointestinal tracts, using a proton pump inhibitor reduces the risk of gastric ulceration when NSAIDs are necessary. NSAIDs interact with many antihypertensive medications, selective serotonin reuptake inhibitors, corticosteroids, and warfarin (ACPA, 2020).

NSAIDs have the potential to cause nephrotoxicity. They inhibit prostaglandin synthesis, which leads to vasoconstriction of the afferent arteriole in the kidney, thus reducing the glomerular filtration rate. Use NSAIDs cautiously in those with renal impairment (Ali et al., 2018).

NSAIDs lead to cardiovascular complications and increase the risk of myocardial infarctions, especially in patients who take high doses over a prolonged period. For those with increased cardiovascular risk, their use should be limited.

Do not use NSAIDs in those with thrombocytopenia (low platelet count). Patients receiving warfarin or heparin should not receive NSAIDs. NSAIDs impede thrombocyte aggregation, which can increase the risk of bleeding.

Anti-Depressant Use in Pain Management

Antidepressant medications are effective for multiple chronic pain types, including neuropathic pain, fibromyalgia, and pain associated with depression. This next section will look at some of the antidepressants used in the management of pain.

Tricyclic Anti-Depressants

Tricyclic antidepressants (TCAs) modify pain by inhibiting the uptake of norepinephrine and serotonin and blocking multiple channels, including the sodium, adrenergic, cholinergic, and histaminergic channels. Medications in this class include nortriptyline, desipramine, amitriptyline, and imipramine.

Nortriptyline and desipramine (secondary amine TCAs) are preferred agents in this class as they have a better side effect profile (Tauben & Stacey, 2020). These agents are often used in managing neuropathic pain or in chronic pain management as adjuvant agents.

TCAs need to be used cautiously in older adults. They have many side effects (Tauben & Stacey, 2020):

  • Constipation
  • Dry mouth
  • Mental status changes
  • Blurred vision
  • Urinary retention
  • Blood pressure changes
  • Tachycardia
  • Heart block

They should be used very cautiously or not at all in those with cardiac or electrocardiographic abnormalities. The analgesic effect is typically noticed in a shorter time and at a lower dose when treating depression. Some patients will have diminishing side effects as their body adapts to the medications (Tauben & Stacey, 2020).

Most TCAs are started at 10 mg per day and titrated up to 75 mg per day in adults. Older individuals rarely tolerate doses of more than 75-100 mg per day. It may take up to 8 weeks before analgesia is appreciated, but pain relief occurs as soon as one week (Tauben & Stacey, 2020).

Serotonin-Norepinephrine Reuptake Inhibitors

Serotonin-norepinephrine reuptake inhibitors (SNRIs) treat neuropathic pain but also manage other types of pain.

Duloxetine (Cymbalta) treats diabetic neuropathy and painful chronic musculoskeletal conditions such as osteoarthritis and chronic low back pain (Pop-Busui et al., 2017). It is also approved for fibromyalgia. Common side effects include insomnia, drowsiness, dry mouth, fatigue, nausea, and dizziness.

Avoid use in those with severe renal insufficiency or hepatic insufficiency. When stopped, it should be tapered slowly due to withdrawal symptoms.

Venlafaxine (Effexor), another SNRI, is used for neuropathic pain, but it is unlabeled. Venlafaxine may lead to increased blood pressure. When stopping the medication, taper it slowly to minimize withdrawal symptoms.

Anti-Epileptic Agents

Gabapentin is approved in adults for post-herpetic neuralgia up to 3600 mg per day in divided doses. Adjust the dose in those with renal disease. It comes in an extended-release form called Gralise. Gabapentin is often used off-label for other neuropathic conditions, including diabetic neuropathy, generalized neuropathic pain, anxiety, and postoperative pain.

Pregabalin (Lyrica) is approved in adults for fibromyalgia, neuropathic pain (diabetes-related), neuropathic pain in those with spinal cord injury, and post-herpetic neuralgias. Pregabalin and duloxetine have regulatory approval for pain management in neuropathic diabetic pain in the United States, Canada, and Europe (Pop-Busui et al., 2017).

Miscellaneous Agents

Topical lidocaine is first-line therapy for post-herpetic neuralgia. Apply the patches to intact skin, up to three patches, for no more than 12 hours in 24 hours.

Muscle relaxants manage acute and chronic pain. Cyclobenzaprine (Flexeril) was initially classified as a tricyclic antidepressant but remade as a muscle relaxer. Side effects are similar between the TCAs and cyclobenzaprine, including sedation, dry mouth, constipation, urinary retention, and mental status changes.

Carisoprodol (Soma) is another commonly used muscle relaxer that can cause dependence. Due to the concerns of dependence, it is not widely prescribed. It should only be used for short periods as it lacks evidence for long-term benefit. The most common side effect of all muscle relaxers is sedation, and it may potentiate respiratory depression in those on controlled substances.


In recent times, opioid therapy has become more commonly used. It was only used for severe acute pain and cancer pain in the past. A recent position paper from the American Academy of Neurology suggested evidence for good short-term pain relief with opioids (Strain et al., 2020). However, no good evidence exists for the continuation of pain relief or improved function with opioids for extended periods without sustaining a serious risk of dependence, overdose, or addiction.

Opioids function by activating opioid receptors that are located in the spinal cord and the brain. The majority of the pain relief related to opioids is due to their actions on the periaqueductal gray (PAG) cells and the descending pain pathways. Opioid receptors are molecules located on the surface of cells, and opioids attach themselves to them and release their effects. As mentioned above, the three different opioid receptors found in the brain are the Mu, Kappa, and Delta receptors. Mu and Kappa receptors are also found in the spinal cord and mediate pain transmission from the brain's peripheral nervous system. The Mu receptor is the most important pain receptor in opioid abuse and treatment. When opioids activate Mu receptors, the most significant potential for pain relief and addiction is initiated. However, Kappa and Delta receptors also play a role in opioid addiction.

Some critical points for opioid prescribing include:

  • Screen for pregnancy.
  • Obtaining and reviewing personal or family histories of a substance abuse disorder.
  • Evaluating the patient's mental status or pertinent behavioral issues.
  • Patients with complex pain issues, mental health conditions, or other serious illnesses should be considered for referral to a specialized pain clinic.
  • Review the patient's medication profile. Is the patient on benzodiazepines or other medications that can potentiate the danger of opioid use?
  • If using opioids, start a trial of short-acting medication. During this trial period, closely monitor the patient for both the positive and negative effects – is it relieving the pain, and how is it affecting the patient's level of functioning and quality of life? Are there any cognitive side effects or safety issues? 
  • Educate patients to store opioid medication safely, preferably in a locked cabinet, and under no circumstances to share opioid medicines with others and properly dispose of unused or expired medications. 

In consultation with the patient, a treatment agreement should be drawn up and preferably signed; it then becomes part of the medical record. Treatment agreements include:

  • Measurable goals for the reduction of pain
  • A plan for a reduction in opioid medication that mirrors the decrease in patient pain and maintains or improves function
  • Quality of life measurements are included in the plan
  • Circumstances where a patient could get prescriptions from other providers


While there are many opioids, morphine is considered by many as a standard comparator for other drugs. Morphine can be given orally, rectally, intravenously, subcutaneously, or intramuscularly.

Morphine is used for moderate to severe acute pain and chronic serious pain. It comes in multiple formulations. It is dosed at 10-30 mg every 4 hours for acute pain for opioid naïve patients.  It is available as a tablet, solution, suppository, and parenteral solution. The immediate-release tablet is dosed 15-30 mg every 4 hours as needed, and the oral solution is dosed 10-20 mg every 4 hours as needed. It can also be given rectally and is often dosed 10-20 mg every 4 hours as needed. Morphine also comes in a controlled release form, a sustained-release form, and an extended-release form.

Side effects of morphine are like other opioid analgesics and include (Strain et al., 2020):

  • Dry mouth
  • Constipation
  • Bradycardia
  • Hypotension
  • Nausea
  • Drowsiness
  • Dizziness
  • Mental status changes
  • Fever
  • Itching
  • Weakness
  • Hypoxia
  • Urinary retention

Morphine should not be used in those with a hypersensitivity to morphine, toxin-mediated diarrheal disease, severe/acute asthma, paralytic ileus, or severe respiratory depression. The extended-release form should not be used in those with gastrointestinal obstruction.

Drug interactions that are commonly seen with morphine include (Strain et al., 2020):

  • Amphetamines may increase the effect of morphine
  • Anticholinergic agents may increase the side effects of morphine (constipation and urinary retention)
  • Antipsychotic agents with morphine may reduce blood pressure
  • Nasal azelastine (Astelin) with morphine enhances the central nervous system (CNS) depression effect
  • Clopidogrel therapeutic efficacy may be reduced with morphine
  • Diuretics' side effects may be increased with morphine
  • Hydrocodone enhances CNS depression
  • Hydroxyzine enhances CNS depression
  • MAO Inhibitors enhance the side effects of morphine
  • Selective serotonin reuptake inhibitors with morphine enhance the serotonergic effect and CNS depression
  • Zolpidem enhances the CNS depression
Table 3: Opioid Tolerance
The FDA defines opioid tolerance as taking, for at least one week or longer, one of the following (Tan, 2019):
  • Oral morphine 60 mg/day
  • Oral oxycodone 30 mg/day
  • Oral hydromorphone 8 mg/day
  • Transdermal fentanyl 25 mcg/hour
  • Oral oxymorphone 25 mg/day
  • Or an equianalgesic dose of any other opioid


Fentanyl can be given as an injection, transdermal patch, an oral transmucosal lozenge, a sublingual tablet, a sublingual spray, a buccal tablet, and a buccal film, and a nasal spray. The transdermal patch is used in opioid-tolerant patients with moderate to severe pain and is often started at 25 mcg per hour and changed every 72 hours.

Fentanyl can be used for multiple reasons, including premedication for surgery, general anesthesia, as an adjunct to general and regional anesthesia, and chronic pain management. The transdermal patch is indicated for around-the-clock pain management in those with chronic severe pain. Fentanyl transmucosal and intranasal are indicated for cancer pain.

While no official dosage adjustment is recommended in those with renal or hepatic impairment, those with mild to moderate renal or hepatic impairment should likely have the dose reduced by 50 percent with the patch. The use is not recommended in severe renal or hepatic impairment.  Transmucosal and nasal spray have no specific recommendations for dose reduction in renal or hepatic impairment.

Common side effects of fentanyl include (Strain et al., 2020):

  • Dry mouth
  • Edema
  • Bradycardia
  • Dehydration
  • Respiratory depression
  • Shortness of breath
  • Diaphoresis
  • Nausea
  • Vomiting
  • Constipation
  • Application site erythema (patch)
  • Weakness
  • Muscle rigidity
  • Mental status changes
  • Headache
  • Sedation
  • CNS depression

As with most opioids, contraindications include hypersensitivity, toxin-mediated diarrheal disease, and paralytic ileus. The transmucosal and nasal forms of fentanyl are typically only used by specialists for opioid-tolerant cancer patients. It should not be used for short-term pain, post-operative pain, and in those with severe respiratory disease.

Exercising with the patch on has the potential to increase the absorption of fentanyl. In addition, patients with a fever may also notice an increase in absorption of the medication. The patch form should not be exposed to external heat as this may increase the medication's absorption. The patch should only be applied to intact skin, contains aluminum, and must be removed before an MRI.

Like many medications, there are multiple potential interactions. Some more common interactions include (Strain et al., 2020):

  • Alcohol may enhance CNS depression
  • Beta-agonists may decrease the serum concentration of fentanyl
  • Amphetamines may enhance the effects of fentanyl
  • Anticholinergic medications, along with fentanyl, increase the risk of urinary retention and constipation
  • Antipsychotic agents may increase the risk of low blood pressure
  • Azelastine nasal spray enhances CNS depression
  • Beta-blockers with fentanyl enhances bradycardia
  • Calcium channel blockers increase the risk of hypotension and bradycardia
  • Hydrocodone may enhance CNS depression
  • Selective serotonin reuptake inhibitors with fentanyl increase serotonergic properties
  • Zolpidem effects are increased


Oxycodone is a schedule II-controlled substance and is available in multiple forms. Immediate release is dosed 5-30 mg every 4-6 hours (lower range for opioid-naive patients). There is also an abuse-deterrent tablet that comes as a 5 mg and 7.5 mg tablet.

The controlled-release tablet is indicated for those who require around-the-clock pain control. It is dosed 10 mg every 12 hours to start and titrated carefully. When changing from immediate release to extended release, start the extended-release at half of the daily dose of oxycodone every 12 hours. When switching from transdermal fentanyl to extended-release oxycodone, substitute 10 mg of extended-release oxycodone every 12 hours for each 25 mcg/hour of fentanyl. The oxycodone should be started 18 hours after removing the transdermal fentanyl patch. It also comes as an oral concentrate and an oral solution. Oxycodone is often combined with other analgesic agents such as acetaminophen, aspirin, and ibuprofen (Strain et al., 2020).

Those with a creatinine clearance of less than 60 mL/min should have the dose adjusted down as serum concentration of oxycodone will increase in renal insufficiency. Those with hepatic impairment should have doses reduced; with the extended-release formulation, the starting dose should be lowered one-third to one-half and slowly titrated up to effect.

Side effects include (Strain et al., 2020):

  • Drowsiness
  • Dizziness
  • Itching
  • Constipation
  • Nausea
  • Vomiting

Less common side effects include dry mouth, headache, abnormal dreaming, blood pressure changes, diaphoresis, weakness, and fever.

Oxycodone is contraindicated in paralytic ileus, significant respiratory depression, hypercarbia, acute or severe bronchial asthma, and GI obstruction.

Caution should be used in those with biliary tract impairment, such as acute pancreatitis, as it may lead to constriction of the sphincter of Oddi. It may lead to an elevation of intracranial pressure (ICP) and should be used carefully for those with intracranial lesions, elevated ICP, or a head injury.

Extended-release tablets may get lodged into the GI tract, including the throat, in those with swallowing issues. It may lead to intestinal obstruction or diverticulitis.

Common drug interactions with oxycodone (Strain et al., 2020):

  • Alcohol may enhance CNS depression
  • Amphetamines may increase the effect of oxycodone
  • Anticholinergic agents may increase the side effects of oxycodone (constipation and urinary retention)
  • Antipsychotic agents with oxycodone reduce blood pressure
  • Nasal azelastine (Astelin) enhances CNS depression
  • Diuretics' side effects may be increased with oxycodone
  • Hydrocodone and hydroxyzine enhance CNS depression
  • MAO inhibitors enhance the side effects of oxycodone
  • Mirtazapine increases CNS depression
  • Rifampin decreases the serum concentration of oxycodone
  • Selective serotonin reuptake inhibitors with oxycodone increase the serotonergic effect and CNS depression
  • Zolpidem increases CNS depression


Hydrocodone, classified as a Schedule II Controlled Substance, is available as a combination pill with a non-narcotic analgesic and by itself in an extended-release form. The combination pill has a short-acting version of hydrocodone and is dosed with 2.5 to 10 mg of hydrocodone every 4-6 hours as needed for moderate to severe pain.

Hydrocodone extended-release is typically dosed 10 mg every 12 hours in treatment-naive patients.  It is used for severe pain requiring around-the-clock dosing of hydrocodone. The dose may be increased every 3-7 days in 10 mg increments.

Those with severe hepatic impairment should start at the lowest dose and titrate up very slowly while monitoring side effects. Caution should be used with renal impairment as plasma concentration may rise.

Side effects include (Strain et al., 2020):

  • Constipation
  • Nausea
  • Vomiting
  • Dry mouth
  • Drowsiness
  • Headache
  • Dizziness
  • Pruritus
  • Nausea

Contraindications to hydrocodone include paralytic ileus, severe asthma, severe respiratory depression, and hypercarbia.

Common drug interactions with hydrocodone (Strain et al., 2020):

  • Alcohol may enhance CNS depression
  • Amphetamines may increase the effect of hydrocodone
  • Anticholinergic agents may increase the side effects of hydrocodone (constipation and urinary retention)
  • Nasal azelastine (Astelin) enhances CNS depression
  • Diuretics' side effects are increased with hydrocodone
  • MAO inhibitors enhance the side effects of hydrocodone
  • Selective serotonin reuptake inhibitors with hydrocodone increase the serotonergic effect and CNS depression
  • Zolpidem enhances the CNS depression


Tramadol is a Schedule IV medication in the Controlled Substance Act. It is indicated for moderate-to-severe pain, and the immediate release form is dosed at 50-100 mg every 4-6 hours for a maximum of 400 mg a day.

Tramadol is also indicated for chronic moderate-to-severe pain. Those who do not need a rapid onset of pain relief and are affected by side effects may be dosed at 25 mg/day and titrated every three days to 50-100 mg every 4-6 hours to a maximum of 400 mg a day. Tramadol also comes in an extended-release form, dosed 100 mg once a day and maybe titrated by 100 mg every five days to a maximum dose of 300 mg a day.

When prescribing tramadol to older adults, use the lower end of the dosage range and titrate slowly. In those over 75 years old, 300 mg a day should not be exceeded, and utilize extreme caution with the extended-release form.

In those with a creatinine clearance of less than 30 mL/min, only the immediate-release formulation should be used with doses of 25-100 mg split every 12 hours (maximum dose of 200 mg a day). In those with severe liver impairment, the immediate release form should be given at a maximum of 50 mg every 12 hours.

Side effects include (Strain et al., 2020):

  • Flushing
  • Dizziness
  • Constipation
  • Nausea
  • Vomiting
  • Dyspepsia
  • Itching
  • Headache
  • Somnolence
  • Insomnia
  • Weakness

Less common side effects include orthostatic hypotension, mental status changes, euphoria, rash, hot flashes, diarrhea, dry mouth, anorexia, joint pain, blurred vision, and sweating.

Patients may experience withdrawal symptoms from tramadol, including nausea, diarrhea, anxiety, pain, sweating, tremors, and rigors. Extended tramadol use may lead to dependence, and these medications should be tapered slowly to reduce the risk of withdrawal symptoms.

Tramadol is contraindicated in individuals hypersensitive to the agent and those with severe liver or kidney impairment. The extended-release tablet should not be used with psychotropic drugs, opioids, hypnotics, acute intoxication with alcohol, centrally acting analgesics, or those with severe respiratory depression, severe asthma, or hypercapnia.

Tramadol increases the risk of seizures. This risk is increased in those who take serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, other opioids, or other drugs that lower the seizure threshold. The risk may also be increased in those who have seizures or are at risk for seizures, such as those who have a CNS infection, cancer, a history of head trauma, or while patients are going through drug or alcohol withdrawal.

Caution should be used in those with respiratory disease as those with significant disease may be at increased risk for respiratory depression.

Common drug interactions with tramadol (Strain et al., 2020):

  • Alcohol enhances CNS depression
  • Amphetamines increase the effect of tramadol
  • Anticholinergic agents increase the side effects of tramadol (constipation and urinary retention)
  • Antiemetics reduce the effects of tramadol
  • The combination of antipsychotics and tramadol lowers blood pressure, increases the risk of a neuroleptic malignant syndrome, and increases the risk of serotonin syndrome
  • Nasal azelastine (Astelin) enhances CNS depression
  • Carbamazepine with tramadol enhances CNS depression; tramadol may reduce the therapeutic effect of carbamazepine
  • Cyclobenzaprine and tramadol, taken together, increases the risk of seizures and increases the risk of serotonin syndrome
  • Diuretics' side effects may be enhanced with tramadol
  • Hydrocodone and hydroxyzine increase CNS depression
  • MAO inhibitors with tramadol increase seizure risk and serotonin syndrome risk
  • Metoclopramide with tramadol increases the side effects of metoclopramide, increases the risk of serotonin syndrome and neuroleptic malignant syndrome
  • Selective serotonin reuptake inhibitors and tricyclic antidepressants with tramadol increase the risk of seizures and increases the risk of serotonin syndrome
  • Warfarin with tramadol may affect the anticoagulant effect
  • Zolpidem enhances CNS depression

Side Effects of Opioids in General

Opioid medications are associated with multiple side effects, including constipation, nausea, vomiting, pruritus, abdominal cramping, sedation, and mental status changes. Multiple interventions are available to reduce side effects (Strain et al., 2020).

Constipation is a frequent issue in those who use opioids. Risk factors for constipation include older age, intra-abdominal pathology, and those who eat a low-fiber diet. Those on opiates should be encouraged to increase fiber intake, drink plenty of fluids, and exercise. Stool softeners (e.g., docusate sodium) and stimulants (e.g., bisacodyl) manage constipation. An osmotic laxative such as polyethylene glycol or lactulose can be used or added to stool softeners/stimulants for resistant constipation.

Antiemetic medication can help treat nausea.

Antihistamines can treat pruritus.

Opioids are associated with somnolence and other mental status changes. Patients do develop tolerance to these symptoms over weeks. Reducing the dose may lessen the mental status changes. An adjunctive medication may be added to lower the opioid dose to help manage the pain. Rarely the addition of a stimulant to manage sedation due to opioid use is used.

Respiratory depression may occur, but it is uncommon when the medication is used carefully.  Starting low and slowly titrating the dose will reduce the risk of respiratory depression. Problems arise with rapid titration, the addition of another drug that may suppress the respiratory drive (benzodiazepine, alcohol, or a barbiturate), or the patient overdoses.

Sedation precedes respiratory depression, so when starting a patient on opioid therapy, encourage them to take the first dose in the office to be monitored or in the presence of a responsible adult who can help monitor the patient. Assess the level of consciousness 30-60 minutes after administering the opioid. Hold the next dose and contact the provider if there is a reduced level of consciousness, the patient has hypoxia or has a respiratory rate of less than 10 per minute.

The most severe risk linked with opioid use is an overdose. Death from overdosing on semi-synthetic opioids occurs every 19 minutes in this country, and after car accidents, it is the second major cause of accidental deaths.

The Role of Naloxone

All clinicians who work with pain patients must ensure that they know naloxone and how it reverses opioid overdose. It reestablishes normal respiration rates for an individual whose respirations have slowed or stopped due to opioid overdose. Currently, there are three major formulations of naloxone (U.S. Food and Drug Administration [FDA], 2020):

  • Injectable naloxone – is given by paramedics, emergency room providers, and other specially trained first responders.
  • Auto-injectable - is marketed under the trade name of Evzio®, and it is a prefilled injection device that is injected quickly into the patient's outer thigh. Once it is activated, the device gives verbal instructions on using it, comparable to automated defibrillators.
  • Prepackaged Nasal Spray – Narcan® and Kloxxado® are the trade name for a prefilled device that does not need to be assembled and is sprayed into the nostril of a supine patient.

Take precautions when administrating naloxone (FDA, 2020). Regardless of the setting, the patient must be continuously monitored until trained emergency personnel arrive. Once the patient has been transferred to a health professional’s care, they will require observation for at least two hours to ensure that respirations do not slow down or stop.

Naloxone is a safe medication. It can sometimes cause withdrawal symptoms that may be unpleasant, but they are not life-threatening, such as headaches, alterations in blood pressure, rapid heartbeat, sweating, vomiting, and tremors (FDA, 2020).

Consider prescribing naloxone with opioids as it can reverse the effects of an opioid overdose.  Individuals considered to be at high risk for overdose include those who (FDA, 2020; Saxon & Strain, 2019):

  • Are taking a benzodiazepine, more than 50 morphine milliequivalents (MME) per day
  • Have obstructive lung disease or sleep apnea
  • Have a mental illness
  • Have a history of heroin use or opioid misuse
  • Have a history of overdose
  • Reports excessive alcohol use
  • Those with difficulty accessing medical care and having others in the home with access to the medication

The risk of overdose death starts at 40 MME in those who have never used opioids. The risk is highest within two weeks of starting therapy, and the risk increases tenfold when doses exceed 80-100 MME.

General Prescribing Rules

When prescribing opioids for acute pain, the prescription should be no longer than the expected length of pain. The typical duration is three days or less, and if more than seven days are needed, good documentation must outline the reason for this course. Treat acute pain with immediate-release opioids and not extended-release medications. Start opioids at low doses in the opioid naïve patient and titrate to effectiveness.

Avoid benzodiazepines in those receiving opioids. If the patient is receiving 120 mg MME and the patient is on benzodiazepines for mental health reasons, the mental health provider should assess the need for the benzodiazepine. Any patient on more than 120 MME a day should be referred to a pain management specialist (Tennessee Department of Health, 2020).

Tapering Protocol

Significant withdrawal symptoms occur when abruptly stopping opiates, including (FDA, 2020; Saxon & Strain, 2019):

  • Sweating
  • Nausea
  • Vomiting
  • Headache
  • Abdominal pain
  • Myalgia

Abruptly stopping benzodiazepines and alcohol can be fatal, but opiate withdrawal is rarely fatal.

Opiate withdrawal could be managed using multiple protocols. One method uses a ten percent reduction per week, and a more aggressive wean would include a 25% reduction every four days. The use of clonidine can be considered to help manage symptoms of opiate withdrawal. If an individual diverts opiates, which a negative urine drug screen may suggest, weaning is unnecessary.

Prevention of Misuse

To prevent prescription drug abuse, the clinician needs to ensure:

  • Patients are assessed and reassessed
  • Treatment agreements are used
  • Prescription monitoring occurs
  • Safe prescription methods are practiced

Patients' risks should be assessed, and contraindications should be immediately identified. Contraindications to opioid treatment include those who have an erratic follow-up, suffer from current untreated addiction, or have poorly controlled mental illness.

When taking a patient history, document the opioid currently prescribed, its dose, the frequency of use, and duration. It is essential to query the state Prescription Drug Monitoring Program (PDMP) to confirm the patient’s medication use (Strain et al., 2020). Also, it is essential to contact past providers to obtain medical records.

Before prescribing controlled substances, an assessment should be done for a history of illegal substance use, alcohol use, tobacco use, prescription drug use, family history of substance abuse and psychiatric disorders, history of sexual abuse, legal history, behavioral problems, employment history, marital history, social network, and cultural background. A history of substance abuse does not prohibit treatment with opioids but may necessitate more intensive monitoring or referral to an addiction specialist.

Multiple tools are available to evaluate opioid risk (Strain et al., 2020).

The Opioid Risk Tool (ORT) is used in primary care to screen adults for the risk of aberrant behaviors when prescribed opioids for chronic pain. It is a copyrighted tool, encompasses five questions, and takes about one minute to use. It classifies a patient as low, moderate, or high risk of abusing opioids. Those who are high risk have a high likelihood of aberrant drug-related behavior. It is not validated in individuals without pain. The five questions include asking about (Strain et al., 2020):

  1. Family history
  2. Personal history of substance abuse (alcohol, prescription drugs, or illegal drugs)
  3. Age (risk is 16-45 years old)
  4. Psychological disease
  5. Preadolescence sexual abuse history

The questions are scored with different points assigned for each question, variable between men and women, and the total score is tallied. The patient is placed into low, moderate, or high risk.

Regular follow-up is important and should occur a minimum of every three months. When assessing the pain patient, the “Five A’s” should be assessed (Strain et al., 2020):

  1. Analgesia
  2. Addiction
  3. Activities of daily living (ADLs)
  4. Adherence
  5. Adverse effects

A follow-up should include urine drug testing to detect medication adherence and illicit and non-prescription drug use. It is critical that the clinician adequately document any interactions with patients, assessments, and results of testing and treatment plans.

Use written treatment agreements between prescribers and patients when controlled substances are used. Agreements help guide the conversation between patient and prescriber. It discusses expectations, risks, and monitoring of the controlled substances (See Table 4).

In addition, obtain informed consent when starting opioid therapy. Informed consent discusses benefits versus risks, including the risk of addiction, physical dependence, sedation, reduced motor skills, and death. An example of a treatment agreement and informed consent is the Tennessee Chronic Pain Guidelines (2020):

Table 4: Points Commonly Seen in Opioid Agreements
  • Early refills will generally not be given
  • The patient will not seek controlled substances from another provider
  • The patient will use only one pharmacy
  • Permission for the prescriber to speak freely with other healthcare providers, pharmacists, and family members regarding opioid use
  • The patient will submit to a urine drug test
  • The patient will safeguard the medications
  • Common side effects of the medication will be discussed

Prescription monitoring programs are available in the majority of states. They provide an online database that lists all prescriptions of controlled substances dispensed to each patient by pharmacy. The prescriber should check the database before prescribing controlled substances. If a patient has an undisclosed prescription for a controlled substance, it is prescription drug misuse.

When abuse/misuse is detected, how should the clinician respond? If it is a single, minor deviation, then provide counseling and more intensive monitoring. Tapering controlled substances to reduce the risk of withdrawal is appropriate in more severe or persistent misuse cases. When diversion is the cause of misuse, immediate removal of the prescription is likely the best course. A referral to an addiction specialist is recommended if a substance abuse disorder is suspected.

An important role of the practitioner is prescribing controlled substances. Controlled substances have inherent risks, so the prescriber needs to realize that the primary goal of prescribing opioids should be to maintain patient safety. A responsible prescriber should follow multiple steps to ensure safe and effective patient care.

Steps a prescriber can take include:

  • Assessment and documentation of a comprehensive history, including medical history, substance abuse history, current medications taken, including dosages, route, and time (including opioids), and psychiatric and psychosocial history.
  • Establish a physical and psychological diagnosis and medical necessity before starting or maintaining opioid therapy. Those with mental illness are at higher risk of abusing medications.
  • Screen for a substance abuse history because substance abusers are at increased risk of misusing controlled substances.
  • Establish goals in therapy regarding pain control and functional goals.
  • Use prescription monitoring programs to help determine patterns of prescription use. There are state-run databases that track controlled substance prescriptions and help find issues with overprescribing and misuse patterns.
  • Urine drug testing can be used to identify non-compliance or aberrant drug use.
  • Consider contraindications before prescribing opioids, such as acute psychiatric instability, uncontrolled suicide risk, opioid allergy, respiratory instability, history or current abuse of substances or alcohol, current use of benzodiazepines, current use of heavy doses of other central nervous system depressants, current use of other medications that have severe drug interactions or those who practice diversion of controlled substances.
  • Judicious utilization of imaging tests and other evaluations as some testing may increase fear, foster activity restriction, encourage maladaptive behaviors, and encourage requests for more opioids.
  • A written agreement between prescriber and patient when opioids are used reduces the risk of abuse, diversion, misuse, and overuse.
  • Discuss the risks and benefits of the medications.
  • Obtain informed consent before prescribing controlled substances.
  • In general, start opioid therapy at low doses with short-acting medications.
  • Use long-acting opioids in high doses only for severe, intractable pain that cannot be adequately managed with short-acting opioids or moderate doses of long-acting opioids.
  • Use caution when titrating long-acting opioids and consider the potential for overdose and misuse.
  • Consider consultation for those who require high-dose opioid therapy.
  • Be the only prescriber of all opioids for a given patient.
  • Monitor for and manage constipation.
  • Prescribe the lowest effective dose and the smallest quantity needed based on the expected length of the pain.
  • Periodically review the treatment plan, including any new information about the patient, their condition, and their pain and progress toward their goals.
  • Keep accurate records.
  • Be compliant with all laws and regulations related to controlled substances.
  • Individualize treatment based on the patient’s prior exposure to opioids, response to treatment, and adverse events.
  • Monitor for aberrant drug-related behaviors.
  • Discontinue chronic opioid therapy in those who repeatedly engage in aberrant drug-related behaviors, do not progress toward established goals, or experience significant side effects. Patients taking the opioid for an extended time should have the medication tapered slowly.

Tips to Reduce Iatrogenic Harm

  • Have an upper dosing threshold. The risk of accidental overdose increases with higher doses of opioids. Prescribers should generally avoid doses of morphine or morphine equivalents more than 90 - 200 mg/day.
  • Use caution with certain medications. For example, methadone should only be used by a prescriber who is extremely comfortable with the medication. Fentanyl is another medication that requires extreme caution as there is unpredictable absorption.
  • With opioid use, respiratory depression is more likely in the older population and cachectic or debilitated. Patients at high risk should be monitored more closely, and opioids should not be given in combination with other respiratory depressants. The dose of opioids should be started at one-third to one-half the typical starting dose in at-risk patients. Titration should be done carefully. Constipation is more likely, and a bowel regime should be prescribed when opioids are used.
  • When starting chronic opioid therapy, it should be started as a therapeutic trial that may last from several weeks to several months. The decision to continue the therapy must be carefully considered based on the trial's outcomes, such as progress toward meeting goals, side effects, changes in the underlying condition causing pain, and any concern for medication misuse or addiction.
  • The greatest risk of opioid use is respiratory arrest and death, which is most significant when therapy is started or increased. Opioid-induced respiratory depression is manifested by the reduced desire to breathe and reduced respiratory rates. The patient will be breathing shallowly, and CO2 retention can exacerbate the sedating effects of opioids. If this is noted, the family should call 911.
  • Opioids should not be used in those with respiratory depression. Titration must be done slowly, and when changing formulations, do not overestimate the converting dosage.
  • Opioid rotation – changing from one opioid regime to another to reduce adverse events and improve therapeutic outcomes – may be considered. Tolerance to one opioid can lessen the analgesic effects, and the use of a different opioid may result in an improved analgesic effect and fewer adverse effects.
  • When opioid rotation is done, the prescriber must determine the approximate equianalgesic dose. This is the ratio used to get about the equivalent analgesic effect.  When switching from one opioid to another, the dose should be reduced by 25 – 50% to prevent adverse effects. Multiple computer programs or applications for mobile devices are available to help with this conversion.
  • Avoid combinations of opioids and benzodiazepines. When these two classes are combined, particularly if more than 100 mg of morphine or morphine equivalents per day are used, the risk of accidental overdose is high.
  • Pay attention to drug-to-drug and drug-to-disease interactions.

Other Controlled Substances


Benzodiazepine, a commonly used medication to control anxiety, works effectively and quickly for those suffering from anxiety and agitation. Unfortunately, they have significant side effects and have issues with tapering and withdrawal. Benzodiazepines became popular agents (they replaced barbiturates) in the 1960s. Chlordiazepoxide (Librium) and diazepam (Valium) were commonly used in the 1960s and 1970s. In the 1980’s alprazolam (Xanax) became a popular agent used for panic disorder, as it became a new diagnosis in the DSM-III. Clonazepam was also a popular medication used in the 1980s.

Benzodiazepines affect the gamma aminobutyric acid (GABA) receptor site – a major inhibitory neurotransmitter (U.S. Department of Justice, 2017). Typically, GABA fastens to postsynaptic GABA-A receptors, which opens the chloride ion channels and slows down neurotransmission. The benzodiazepines enhance the opening of the ion channel, reducing neuronal firing in the brain, leading to less anxiety. Benzodiazepines are absorbed through the GI tract and then absorbed in the small intestine within 30 minutes.

Depending on the condition, benzodiazepines can be prescribed on an as-needed or routine basis. The fixed-dose will more predictably control symptoms, especially in those with constant or frequent anxiety. When given on an as-needed basis, they work well when the anxiety is less constant, such as panic disorder. As needed, benzodiazepines may interfere with cognitive behavioral therapy. Patients are supposed to get more comfortable with emotions related to panic and work through their emotions and automatic thoughts without reliance on a pill.

Benzodiazepines have the potential to reduce anxiety significantly but have the potential to lead to abuse, dependency, and many side effects. Common side effects of benzodiazepines include (U.S. Department of Justice, 2017):

  • A change in mental status
  • Sedation
  • Falls
  • Psychomotor impairment
  • Weight gain

With the continued use of benzodiazepines, tolerance will develop. In addition, dependence may occur within months of starting therapy. Individuals who have been on benzodiazepines for an extended period should be weaned to limit withdrawal symptoms or rebound anxiety.

Benzodiazepines are tapered very slowly depending on the patient's dose (U.S. Department of Justice, 2017). It may take months to taper the medication. For individuals on over 2 mg of daily alprazolam, the dose may be reduced by 0.25 mg every two days, and once the dose is less than 2 mg a day, reducing the dose by 0.125 mg every two days may be used to taper the medication. A 5% reduction every two days may be considered. This 5% reduction may be extrapolated to other benzodiazepines.


Barbiturates are sedative-hypnotics and have anti-anxiety properties. They are addictive and have the potential to lead to overdose. These medications have been less commonly used since the 1970s as benzodiazepines increased in popularity. Barbiturates are still sometimes used for those with a seizure disorder. Medications in this class include phenobarbital, pentobarbital, secobarbital and amobarbital. Some medicines have short half-lives, while others have half-lives lasting up to two days. The most commonly prescribed drug in this class is phenobarbital and its indicated for sedation and seizure management (U.S. Department of Justice, 2017). Barbiturates are associated with drowsiness, disinhibition, and euphoria. When prescribed, levels must be monitored as this class has a narrow therapeutic index.


Carisoprodol (Soma and Vanadom) is a skeletal muscle relaxant used for a maximum of 2-3 weeks for acute discomfort associated with painful musculoskeletal conditions at a dose of 250-350 mg three to four times a day (, 2021). It is a schedule IV-controlled substance and is given with or without food. Common side effects include (, 2021):

  • Drowsiness
  • Dizziness
  • Headache
  • Occasionally seizures

It has the potential to increase respiratory depression when mixed with opioids.

It should be used cautiously in those with abuse issues and is associated with physical and psychological dependence and tolerance. It has a rapid onset of action with a duration of action of 4-6 hours. Withdrawal can occur, particularly in those who have used it for longer than two to three weeks.

Case Study #1: John

John is a 38-year-old male with chronic back pain due to three herniated discs and spinal stenosis, first diagnosed three years ago after a motor vehicle accident. He currently rates the severity of his back pain as a 9/10 and has been unable to work as a plumber due to his pain.

The pain can be described as dull and constant, with occasional sharp exacerbation in the low back, with the pain increasing with bending, prolonged standing, and walking. The patient denies any loss or change of bowel/bladder control, history of IV drug use, recent infection, progressive neurological complaints, night pain, night sweats, weight loss, or fever. The pain occasionally radiates into the right buttock. The patient can do all his daily living activities but reports poor sleep at night.

He has a past medical history of hypertension and recently developed stage II chronic kidney disease secondary to hypertension and excessive use of ibuprofen. His only current medication is lisinopril to control his blood pressure.

He has had multiple treatment modalities, including four rounds of physical therapy, chiropractic treatment, and numerous medications. He tried to control his back pain with acetaminophen, naproxen, ibuprofen, the lidocaine patch, and topical non-steroidal anti-inflammatory agents without relief. The patient experienced significant tremors and increased blood pressure while on tramadol. A series of epidural injections did not help. Surgery was discussed, but the patient refused this option.

John is married and has one daughter who lives over 500 miles away from her biological father. He has limited financial means, lives paycheck to paycheck, and has a prior history of alcohol abuse but has not had a drink in five years. He is currently a smoker. He denies any history of substance abuse and has no family history of alcohol or substance abuse.

A physical exam showed a patient with a slow, deliberate gait, a limited range of motion in the spine, and no obvious deformity, swelling, or erythema. There is mild tenderness on the right side of the spine from L4 to S1 and tenderness in the right sacroiliac joint. Normal reflexes, sensation, strength, and no atrophy are noted in the lower extremities. The straight leg raise test is normal.

An MRI showed a herniated disc at the L5/S1 level and mild spinal stenosis one year ago.

The Opioid Risk Tool was administered, and it was determined that the patient was at moderate risk for opioid abuse. He signs a written opioid treatment agreement that outlines the conditions of opioid therapy. His past medical records were verified, suggesting he is not lying.

The patient is prescribed hydrocodone-acetaminophen 5 mg/500 mg, two tablets every six hours as needed (56 tablets) for one week.

Five days later, he calls for an early refill and reports that the medication is not helping his pain, and he lies around all day.

He comes back into the office for a re-evaluation. He reports he needed to take more pain medication than prescribed. His wife confirms that he has been lying around all day, and she believes it is because he is having so much pain. It was reviewed with the patient that he violated the opioid agreement. A urine sample showed no illicit substances or medications that would not be expected in the urine.

While the patient is at moderate risk of abusing the medication, his past medical history was confirmed. He was referred to a psychiatrist and a pain specialist. He was agreeable to both. The patient saw the psychiatrist, was diagnosed with depression, and was started on sertraline. He could get to the psychiatrist within one week, but the pain specialist appointment was four weeks out. The psychiatrist was unable to make an assessment related to opioid abuse.

With the help of the pain specialist, oxycodone ER 10 mg was ordered every 12 hours. The patient was told to follow up in one week to assess effectiveness. After one week, the patient reports he is more functional but still in a lot of pain. The dose of oxycodone ER was increased to 15 mg every 12 hours. After one more week, he was given oxycodone IR 5 mg one hour before exercise. This allowed the patient to function well and begin participating in an exercise program. The patient was ordered a bowel stimulant (Senna) with a stool softener (Colace) to prevent constipation.

The patient is prescribed fourteen pills of oxycodone ER 10 mg (to be taken twice a day) and seven pills of oxycodone IR 5 mg (to be taken once a day before exercise) once a week. Part of the agreement was that the medications were to be given by the patient’s wife to reduce the risk of misuse.

Case Study #2: Ms. L

Ms. L is a 49-year-old female with a history of bilateral knee pain. She currently rates the pain as an 8/10 in her right knee and a 5/10 in her left knee.

She takes MS Contin 60 mg every 12 hours with an immediate-release tablet of morphine dosed 15 mg every 8 hours as needed (she averages one dose a day) and has been using this regime for the past six months. Still, over the last month, she has not been getting adequate relief from her pain and has been progressively disabled and has, therefore, stopped exercising.

The pain is attributed to osteoarthritis and has progressively worsened over the last 1-2 years. She has a past medical history of anxiety and depression but does not take any medication for these conditions. She has a past surgical history of a hysterectomy approximately three years ago. She takes no other medications and has no known allergies.

She has no history of alcohol, drug, or substance abuse. She has a strong family network, including a supportive husband of 25 years and two sons who live nearby.

The physical exam is significant for obesity (BMI of 34). Due to pain, she has crepitus in both knees and cannot fully extend the right knee. An x-ray demonstrates moderate arthritic changes in both knees. The patient is unwilling to consider surgery on her knees.

After the state’s prescription monitoring program database was accessed, it was determined that she had not gotten any controlled substances other than morphine for the last two years. A urine drug screen was positive for morphine but no other substances.

The nurse practitioner offers meloxicam and a knee injection in her right knee. She reports not using any breakthrough morphine dosing on the follow-up appointment. The nurse practitioner increases the dose of meloxicam, gives her an injection in her left knee, and has a conversation about weaning the morphine dosing. The patient is agreeable to weaning the dose of morphine by 10 mg every 1-2 weeks with frequent follow-up to assess pain control. She is agreeable to a follow-up in two weeks. At that point, there is a notable improvement in her pain level and the amount of enjoyment she gets out of life. Over the next year, she can wean off morphine while continuing on the meloxicam. In addition to the meloxicam, she lost 20 pounds, which she attributes to her improved quality of life and enhanced ability to function.


Pain is a disagreeable sensory and emotional experience connected with actual or potential tissue damage. Many conditions can cause pain. Understanding, assessing, and treating these conditions is vital for adequately managing pain.

The nurse practitioner's role is to perform a thorough initial pain assessment and an ongoing assessment of pain. Many options are available for pain management, including non-pharmacological options, non-opioid medications, opioid medications, and adjunctive medications. Opioid analgesics, while very good at managing pain, have led to many social and legal problems, including overuse and diversion.

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Implicit Bias Statement

CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.


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