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Addiction Disorders

4 Contact Hours including 4 Advanced Pharmacology Hours
Meets Kentucky APRN Requirement
This peer reviewed course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Registered Nurse (RN)
This course will be updated or discontinued on or before Tuesday, August 22, 2023
Outcomes

≥92% of participants will report an increase in knowledge regarding how to assess and manage addiction.

Objectives

After completing the course, the learner will be able to:

  • Define addiction.
  • Compare and contrast substance use disorder, opioid use disorder, alcohol use disorder, and cannabis use disorder.
  • Describe the risks of abuse and addiction with opioid medications.
  • List the diagnostic criteria for opioid use disorder.
  • Summarize the evaluation of a patient with substance use disorder.
  • Compare and contrast the use of methadone, buprenorphine, and naltrexone in the management of opioid use disorder.
  • List five professional standards of 201 KAR 20:065 for prescribing Buprenorphine-Mono- Product or Buprenorphine-Combined-with-Naloxone by APRNs.
CEUFast Inc. did not endorse any product, or receive any commercial support or sponsorship for this course. The Planning Committee and Authors do not have any conflict of interest.

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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)

Introduction

According to the American Society of Addiction Medicine, "Addiction is a treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual's life experiences." (ASAM, 2020). Individuals with addiction utilize substances or participate in actions that grow habitually and often persist, notwithstanding dangerous outcomes.

In addition, the American Society of Addiction Medicine suggests addiction is "a primary, chronic disease of brain reward, motivation, memory, and related circuitry," with a "dysfunction in these circuits" being reflected in "an individual pathologically pursuing reward and relief by substance use and other behaviors." (Comer et al., 2015).

Many people consider addiction a disease. A disease is defined as a disorder of function or structure that produces signs or symptoms. Addiction has defined causes and observable consequences. Addiction is different from other chronic diseases. It has high negative externalities, such as those who are addicted often engage in criminal activity, engage in violent behavior and engage in harmful behavior. Nonetheless, it is still classified as a disease.

Addiction is like many chronic diseases, such as diabetes mellitus and hypertension, for multiple reasons. Like other chronic diseases, addiction can be challenging to manage behaviorally, responds to ongoing treatment, requires lifelong management, and results from certain genetic and environmental factors.

Drugs strongly affect society. Most drug users can function in society while using illicit substances. Seventy percent of people who use drugs are employed. Ten to twenty percent of workplace deaths involve drugs, and substance use significantly affects absenteeism, productivity, and injury. Two-thirds of people who report partner violence report alcohol was involved, and forty percent of traffic fatalities involve alcohol (Substance Abuse and Mental Health Services Administration, 2021).

Substance abuse is a significant problem among prisoners. Eighty percent of state and federal prisoners report a history of substance use, and fifty percent report a substance use disorder. Thirty-three percent report using at the time of their offense, including using while committing the crime, committing a crime to fund drug use, or a crime related to manufacturing and selling drugs (NIDA, 2020b).

Statistics

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
SubstanceHealth care costs in dollarsOverall cost in dollarsYear
Tobacco168 billion300 billion2010
Alcohol27 billion249 billion2010
Illicit Drugs11 billion193 billion2007
Prescription Opioids26 billion78.5 billion2013

Substance Abuse

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

  • In 2016, 48.5 million individuals in the United States misused prescription drugs or used illicit drugs. Sixty-six percent of the 630,000 drug overdose deaths were due to illicit 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).
  • 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).
  • Research shows that white individuals account for 88% of those who reported non-heroin opioid substance abuse, and most of these individuals lived in rural settings.
  • About 53 percent of people who have ever tried heroin develop heroin abuse or dependence (Strain et al., 2020).
  • Approximately 10-20 percent of people who get a prescription of opioids for non-cancer pain go on to develop an opioid use disorder (OUD) (Degenhardt et al., 2015).

Definitions

Prescription drug misuse involves using prescription medication in a method or intent inconsistent with how it was prescribed. Misuse includes using medication 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.

Susceptible individuals are at risk to misuse medications that stimulate the brain's reward center, including opioid analgesics, stimulants, benzodiazepines, or tranquilizers. Drug abuse is when drugs are not used medically or socially appropriately. 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.

Psychological dependence is the perceived need for the substance. 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. At this point, there is typically a loss of control regarding drug use. The drug is continued despite severe medical and social consequences. Tolerance, increasing doses of the medication needed to produce an equivalent effect, is typically seen by the time addiction is present. Physical dependence can occur without addiction. Individuals who take chronic pain medication may be dependent on the medication but not addicted.

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 those with a 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:

  • 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

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 intensity of treatment 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.

Addiction leads to functional and structural alterations in the brain. Volume loss is seen with cocaine, opiate, and alcohol dependence and in those with 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.

Neurobiology

Many brain functions and their structure are affected by addiction, including reward, executive function learning and memory, motivation, and inhibitory control. These functions are critical to living and living functionally.

Dopamine is a chemical that is linked to the reward center. Food and sex stimulate the dopaminergic center and can partly be described as essential for survival. Opioids work on the same reward center and increase dopamine levels even more than food and sex. Amphetamines can increase dopamine by tenfold.

Repeated drug use changes the brain. For example, D2 receptors are lower in those who repeatedly use cocaine. Lower dopamine levels are problematic because dopamine D2 receptors control behavior based on potential consequences. Therefore, this physiological mechanism may partially explain negative choices made by cocaine users.

Social circumstances and stress can significantly affect drug use. When rats were caged (more stressed), they used more cocaine than those who were able to roam free (NIDA, 2020a).

Another study showing how stress affects drug use looked at those fighting in the Vietnam war. It showed that 60-70 percent of men who had opiate addiction in Vietnam were not using opiates 8-10 months after their return, suggesting that stress increases drug use.

Opioids

In recent times opioid therapy has become more commonly used. In the past, it was only used for severe acute pain and cancer pain. A recent 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 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 types of opioid receptors found in the brain: 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. 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; it includes 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 that contain less than 200 milligrams of codeine per 100 milliliters or per 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.

Appropriate Opioid Use

Understanding how to use opioids appropriately will reduce the risk of addiction. The management of pain may include medications, behavioral interventions, physical medicine, neuromodulation, medical interventions, or surgery. A multidisciplinary approach is typically used in the management of chronic pain.

Current treatments in chronic pain management result in approximately a 30% reduction in pain. One of the problems encountered is that general practitioners have limited training in the management of chronic pain. The use of a pain management specialist is often needed to manage pain properly.

The treatment plan should be established before initiating treatment. In this plan, the patient and the provider should discuss the benefits, risks, and alternatives before starting treatment. In addition, the clinician needs to discuss how the patient will be monitored, including how the patient will be evaluated for potential misuse of the prescribed medication. The use of written documents is often included in the plan. Documents may include agreements, treatment plans, and informed consent. It is essential that the clinician document that decision-making was implemented, including informed consent, goal setting was discussed, and a monitoring plan was defined.

When high doses of opioid prescriptions are given, there is an increased risk of overdose death. Therefore, the clinician must discuss and limit the amount of opioids prescribed. The CDC recommends that providers prescribe no more than 90 morphine milliequivalents per day (Dowell et al., 2016).

The World Health Organization (WHO) analgesic ladder was created to manage cancer pain and was published in the 1980s (World Health Organization, 2021). Key points of the analgesic ladder include:

  1. Medications are given through the most comfortable route (preferably orally).
  2. A stepwise approach should be followed, starting with non-opioid medications with or without adjuvant medications.
  3. Managing mild to moderate enduring or progressive pain with opioids, with or without adjuvant medications, with or without non-opioids.
  4. Considering the use of more potent opioids such as morphine with or without adjuvant medications with or without non-opioids for persistent pain or increasing pain.
  5. Administering analgesic pain medication used for moderate to severe chronic pain on a fixed schedule (not as needed).

This approach is 80-90% effective.

Adjunctive medications enhance the analgesic effect, reduce side effects, and assist with co-existent symptoms. Patients respond distinctively to different treatments regarding efficacy and side effects. Trial and error are often used in the treatment of chronic pain.

When starting therapy, the dose should be initiated at a low dose and titrated to obtain pain control and minimize side effects. Tolerance often develops as a patient gets used to the medication.

Treatment is typically started with a short-acting medication, and the medication is then titrated upwards to control pain while side effects are monitored. After determining the dose of the medication required to provide adequate pain relief with minimal side effects, the medication can then be converted to a sustained release form and be administered once or twice a day. When a long-acting medication is used, breakthrough medication can be given.

A periodic review of the patient's pain and clinical status is essential to assure that opioids need to be continued or discontinued. Any change in the patient's state of health, degree or nature of pain, mental health, and overall function should be noted. The clinician and patient should review the proper dosage and schedule of medication. Decisions on the benefits of pain management should focus on previously decided upon goals. A positive response to treatment can include reducing pain, improving quality of life, or improved function.

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

Steps a prescriber can take include (Manchikanti et al., 2012):

  1. Assessment and documentation of a comprehensive history including medical history, substance abuse history, current medications including dosages, route and time (including opioids), psychiatric and psychosocial history.
  2. Establishing a physical and psychological diagnosis and establish medical necessity before starting or maintaining opioid therapy. Those with mental illness are at higher risk of abusing medications.
  3. Screening for substance abuse history because substance abusers are at increased risk of misusing controlled substances.
  4. Establishing goals in therapy regarding pain control and functional goals.
  5. Using prescription monitoring programs to help determine patterns of prescription use and reducing abuse of medications. These are state-run databases that track controlled substance prescriptions and help find issues with overprescribing and misuse patterns.
  6. Urine drug testing can be used to identify non-compliance or aberrant drug use.
  7. 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.
  8. 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.
  9. A written agreement between prescriber and patient when opioids are used reduces the risk of abuse, diversion, misuse, and overuse.
  10. Discussing the risks and benefits of the medications.
  11. Obtaining informed consent before prescribing controlled substances.
  12. In general, starting opioid therapy at low doses with short-acting medications.
  13. Using 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.
  14. Using caution when titrating with long-acting opioids and consider the potential for overdose and misuse.
  15. Considering consultation for those who require high-dose opioid therapy.
  16. Being the only prescriber of all opioids for a given patient.
  17. Monitoring for and managing constipation.
  18. Prescribing the lowest effective dose and the smallest quantity needed based on the expected length of the pain.
  19. Periodically reviewing the treatment plan, including any new information about the patient, their condition and their pain, and progress toward their goals.
  20. Keeping accurate records.
  21. Being compliant with all laws and regulations related to controlled substances.
  22. Individualizing treatment based on the patient's prior exposure to opioids, response to treatment, and adverse events.
  23. Monitoring for aberrant drug-related behaviors.
  24. Discontinuing chronic opioid therapy in those who repeatedly engage in aberrant drug-related behaviors, do not progress toward established goals, or those who experience significant side effects. Patients who have been taking the opioid for an extended time should have the medication tapered slowly. A 10% taper per week will minimize the symptoms of withdrawal. Some recommend a faster taper, such as 20 – 50% per week for those not addicted.

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 exceptionally comfortable with the medication. Fentanyl is another medication that requires extreme caution as there is unpredictable absorption – especially with the patch.
  • With opioid use, respiratory depression is more likely in the older population and those who are cachectic or debilitated. Patients at high risk should be monitored more closely, and opioids should not be combined 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 common, and a bowel regime should be prescribed when opioids are used.
  • When starting opioid therapy, it should be initially started as a therapeutic trial. Then, the decision to continue the therapy must be carefully considered based on the trial 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 most significant risk of opioid use is respiratory arrest and death, and this risk is greatest when therapy is started, or the dose is 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. For example, 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, it requires the prescriber to determine the approximate equianalgesic dose, as this ratio is 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, mainly 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.

The Centers for Disease Control and Prevention (CDC) 2016 Guideline for Prescribing Opioids for Chronic Pain (Dowell et al., 2016) reiterates the need for adequate pain control and the challenges involved, particularly in chronic pain control. It recommends that providers utilize the "full range of therapeutic options" to treat chronic pain. The report states that it is hard to quantify the number of individuals who could benefit from long-term opioid medications.

The report states that between 1999 and 2014, more than 165,000 people died from opioid overdoses. Using DSM-IV diagnosis criteria, in 2013, approximately 1.9 million individuals either abused or were dependent on opioids. Research has found practices that have contributed to the opioid overdose epidemic, the most important of which are prescribing high doses of opioids, overlapping opioid and benzodiazepine prescriptions, and the use of extended-release opioids for acute pain (Dowell et al., 2016).

Prevention of Misuse

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

  • 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. Also, it is essential to contact past providers to obtain medical records.

Before controlled substances are prescribed, 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 should be assessed. 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. The Opioid Risk Tool is a tool 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 to abuse 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 family and personal history of substance abuse (alcohol, prescription drugs, or illegal drugs), age (risk is 16-45 years old), psychological disease, and preadolescence sexual abuse history. The questions are scored with different points assigned for each question, which is variable between men and women, and the total score is tallied.

Regular follow-up is essential and should occur at a minimum of every three months. When assessing the pain patient, the five A's should be assessed: analgesia, addiction, activities of daily living, adherence, and adverse effects. Part of follow-up should be urine drug testing, which can 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.

Written treatment agreements, which should be used between prescribers and patients when controlled substances, help guide the conversation between patient and prescriber. It discusses expectations, the risks, and the monitoring of the controlled substances. (Table 2).

Table 2: Points Commonly Seen in Opioid Agreements
  • Early refills will generally not be given.
  • The patient will not pursue controlled substances from another provider.
  • The patient will use only one pharmacy.
  • Permission is granted for the prescriber to speak freely with other health care providers, pharmacists, and family members regarding the patient’s opioid use.
  • The patient will submit to urine drug tests.
  • The patient will safeguard the medications.
  • Common side effects of the medication will be discussed.

As of 2021, prescription monitoring programs are available in all states except Missouri. They provide an online database that lists all prescriptions of controlled substances dispensed for each patient by pharmacies. Ideally, the prescriber should check the database before prescribing controlled substances. If a patient has an undisclosed prescription for controlled substances, it is prescription drug misuse.

When abuse/misuse is detected, how should the clinician respond? If it is a single, minor deviation, then counseling and more intensive monitoring may be needed. 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. If a substance abuse disorder is suspected, a referral to an addiction specialist is recommended.

The Role of Naloxone

Naloxone is a drug that is used to reverse an opioid overdose rapidly. It reestablishes typical respiration rates for an individual whose respirations have slowed or stopped due to opioid overdose. Currently, there are three formulations of naloxone.

  • Injectable naloxone: It is given by paramedics, ER physicians, and other specially trained first responders.
  • Auto-injectable: This is marketed under the trade name EVZIO®, and it is a prefilled injection device 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® is the trade name for a prefilled, needle less device that does not need to be assembled and is sprayed into the nostril of a supine patient.

Both EVZIO® and NARCAN® are used for emergencies in the home. Laws regarding naloxone prescription and administration vary from state to state.

Take precautions when administrating naloxone; regardless of the setting, the patient must be continuously monitored until trained emergency personnel arrive. Once the patient has been transferred to a health professionals' care, they will require observation for at least another 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).

Substance Use Disorder

Substance use disorder (SUD) is a complex condition where uncontrolled use of a substance is detrimental. SUD is a broad term that encompasses the uncontrolled use of a wide range of substances.

A 2017 survey showed that 7.2 percent of those over twelve had a SUD over the last year, which breaks down into 5.4 percent with an alcohol use disorder and 2.8 percent with illicit drug use disorder (Substance Abuse and Mental Health Services Administration, 2018).

Risk factors for substance use disorder include (McKay, 2020): sleep difficulties, low motivation, co-morbid mental health diagnosis, history of treatment failures, poor social support, and high stress levels.

Assessment for SUD includes taking an inventory of the patient's drug use, including the type of drugs, the amount, and frequency. In addition, any consequences of drug use should be explored. A complete assessment includes interviewing the patient and family members and previous medical reports. In addition, the clinician should evaluate the patient's desires to change and their stage of change. A complete medical evaluation may include medical, surgical, psychiatric diseases; laboratory evaluations; and family and social issues.

A drug history assessment should be done in a non-judgmental way to improve honesty by the patient when taking the assessment. Start with asking about socially acceptable substances and move to illicit drugs. Ask about caffeine, nicotine, tobacco, alcohol, sedatives/hypnotics, stimulants, opioids, marijuana, cocaine, heroin, hallucinogens, and inhalants. The clinician should question any "other" substances, as many novel substances (such as bath salts, synthetic cannabinoids) have been used.

In addition to the type of substance used, ascertain the pattern of use, last use, frequency of use, and quantity used. The route of drug use should also be identified (e.g., oral, inhalation, injection, intranasal). Invasive routes of delivery suggest a more severe disorder potentially complicated by more severe complications (e.g., injection use associated with hepatitis/HIV and intranasal use associated with not only infectious disease but sinus perforation).

The spectrum of substance use provides a framework to understand how to classify the individual's risk. The spectrum includes abstinence, low-risk use, risky use/at-risk use/hazardous use, and harmful use; as the patient moves up the spectrum, the consequences increase. Abstinent individuals are at no risk from substances and will not have any consequences. Individuals classified as low risk have more risk than those who are abstinent, but the consequences are still relatively low. No use of opioids is considered safe.

Unhealthy use is noted at the next step on the substance use spectrum, where the individual places themself at risk and may start to notice some consequences of substance use. When an individual gets to the harmful use spectrum, substance use disorder is recognized. Substance use disorder can be classified as mild, moderate, and severe.

A screening test for other drugs should include a single question in primary care, which is validated as a brief screening test. The question to ask is, "how many times in the past year have you used an illegal drug or used a prescription drug for non-medical reasons?" This question is just as sensitive and specific as a drug abuse screening test, where an affirmative response has 100 percent sensitive and is 74 percent specific for a drug use disorder.

General Treatment Strategies for Substance Use Disorder

Individuals at risk for relapse among those in treatment include (McKay, 2020) those with low motivation after several weeks of treatment, hanging out in areas where use is common (e.g., bars, parties where substances are being used), ongoing craving, continued use, spending time with people who support/encourage substance use after several weeks of treatment.

More intensive monitoring may need to occur in those who are not achieving early treatment goals, including not developing coping behaviors, not developing sources of social support, not committing to abstinence, and not attending meetings/appointments directed at enhancing sobriety (McKay, 2020).

Psychosocial interventions are critical in the management of substance use disorders. These include counseling, teaching patients about self-management skills, and mutual help groups. Clinicians should help clients attain self-management skills, help them set appropriate goals, identify barriers, and create a plan to defeat barriers (McKay, 2020). Self-management also includes encouraging patients to engage in healthy lifestyles such as healthy eating, regular exercise, and stress management.

It is also critical that those suffering from addiction need to be connected to other sources of support, including maintaining employment, engaging in volunteer work, engaging in hobbies, educational endeavors (such as parenting classes and employment training), and participating in help groups.

A significant part of treatment is relapse prevention. Relapse prevention includes:

  • education of potential triggers of relapse
  • early warning signs of relapse
  • strategies to respond to triggers and early warning signs of relapse
  • patients should identify supportive individuals, including family members, friends, and sponsors

Monitoring clinical status can be done using standardized quantitative instruments that have been shown to detect improvement and deterioration. Monitoring will provide insight to both the clinician and provider regarding progress or deterioration in their battle with addiction and offer clues when more rigorous intercession is indicated. It also provides a platform for communication between provider and patient. These tools are more likely to identify early relapse when patients are more likely to be open to more rigorous intercession (McKay, 2020).

Key features that are measured include:

  • Assessment of any recent use
  • How much has the patient been using (number of days of use or average amount of usage)
  • Degree of cravings
  • Degree of depression or sleep difficulty
  • Any exposure to high-risk situations or individuals
  • Involvement in treatment programs
  • Employment status and engaging in activities that provide meaning
  • Degree of social support

Continued care in those with substance abuse disorder is more effective than no treatment in improving outcomes. Interventions used in continued care of those with SUD include case management, couples counseling, telephone calls, home visits, and linking patients to services.

Recovery management, which focuses on the long-term management of addiction, involves regular monitoring of patients and their substance abuse progress. Mixed results regarding the effectiveness of these programs have been demonstrated (McKay, 2020). Strategies used in this program include a clinical evaluation every few months and testing for substance abuse. If a need for more intensive treatment is indicated, the patient is referred to a linkage community program to help get the patient into more intensive treatment.

Extended continuing care offers multiple interventions, including an initial in-person evaluation with follow-up telephone calls. It includes evaluating risk factors and protective factors to help assess the patient's risk of relapse. The use of cognitive-behavioral therapy is an integral part of the program. Contact with a provider occurs every week for two months, then every other week for one year, and then once a month. When an individual is identified as high-risk, they get stepped-up care. Research that is based on this model has found mixed results (McKay, 2020).

Other interventions that may be used in those with substance use disorder include home visits by a nurse, mobile texting, intensive case management, extended employee assistance programs, couples relapse prevention, smartphone-based automated recovery support, and mindfulness-based relapse prevention.

Opioid Use Disorder

While opioids are used for pain relief, they have the potential to be abused. Not only do they have analgesic properties, but they can cause euphoria and depress the central nervous system. Opioid use disorder (OUD) is a chronic, recurrent problem that many individuals struggle with for years. It is associated with significant morbidity and mortality and can lead to many adverse health outcomes, including death from overdose, hepatitis, and HIV. OUD can take many forms and may include the use of heroin, misusing prescription opioids, or the use of diverted opioids (Strain et al., 2020).

Treatment of OUD can include non-pharmacologic options, medication-assisted therapy (MAT), or a combination of the two. MAT includes the use of opioid agonists (buprenorphine and methadone) and opioid antagonists (naltrexone).

Table 3: Opioid Definitions
  • Opioid – A substance that can be synthetic or natural that acts on the opioid receptors. These agents relieve pain, cause euphoria and depress the central nervous system.
  • Opiates – a subclass of opioids made up of compounds that naturally occur, include the opium poppy. Examples include codeine and morphine.
  • Synthetic opioids – include tramadol, fentanyl, and methadone.
  • Semi-synthetic opioids – hydrocodone and oxycodone.
  • Opium – Extracted from the opium poppy. It is a primary source of many narcotics, including codeine and morphine. More common in Asia and the Middle East. It is typically consumed by smoking.
  • Heroin – A morphine derivative that is typically injected but can be snorted.
  • Endorphin – a subclass of opioids made up of endogenous peptides that lead to pain relief and include dynorphins, enkephalins, and beta-endorphins.

It is estimated that in the United States, 2.1 percent of individuals over the age of 12 or 5.7 million people have used heroin at one time, and 0.2 percent or 431,000 people have used it in the last month (SAMHSA, 2019). Heroin use has increased significantly over the last couple of decades, with rates doubling between 2002 and 2018 (Han et al., 2020). Overdose deaths from heroin were approximately 15,000 people in 2018, which equates to five deaths for every 100,000 Americans, but the percentage of death rates has decreased 4.1 percent between 2017 and 2018 (Centers for Disease Control and Prevention; National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention, 2020).

In 2017, in the United States, there were 70,237 drug overdose deaths, and 47,600 were caused by an opioid. In 2018, 67,367 drug overdose deaths occurred, and 46,802 involved an opioid. While there was a decrease in drug overdose deaths, the deaths from synthetic opioids increased by 10 percent, probably due to illicitly manufactured fentanyl (Wilson et al., 2020). The use of opioids among pregnant women has also increased. Between 1999 and 2014, the rate of OUD at hospital delivery increased from 1.5 cases to 6.5 cases per 1000 deliveries (Strain et al., 2020).

Opioid receptors are in the central nervous system and the peripheral nervous system. Stimulation of the mu receptors in the central nervous system can lead to euphoria, respiratory depression, analgesia, and miosis. When the peripheral mu receptors are stimulated, there is resultant cough suppression and constipation (Strain et al., 2020). Opioids act on different neurotransmitters, including glutamate, dopamine, and gamma-amino-butyric acid.

Heroin has a half-life of approximately thirty minutes, but its effects are much longer (up to five hours) because of active metabolites. Heroin has a quick onset of action as it crosses the blood-brain barrier quickly due to its lipid solubility, typically within 20 seconds (Strain et al., 2020).

Clinical Presentation

Patients with OUD may present very differently depending on their current state. They may be acutely intoxicated, in opioid withdrawal, or completely asymptomatic. Acutely intoxicated individuals may be sedated, have injection marks, have pinpoint pupils, or slurred speech. Patients in withdrawal may present with a runny nose, sweating, yawning, myalgia, agitation, anxiety, sleeping difficulty, diarrhea, nausea, vomiting, dilated pupils, and abdominal cramping.

Those who have severe OUD be involved in illegal activity to fund their drug habit. When the disease becomes severe, engaging in activities to fund the drug habit may be a central component of the individual's existence. Many people with a drug habit who engage in illegal activity are not necessarily sociopathic. When the drug habit is controlled, patients often return to "normal" lives.

Medical Complications of OUD

Individuals with OUD often have many health complications. Individuals may appear in poor general health, but some with a mild disorder may appear healthy. Infections are commonly associated with OUD. Injection drug users are more likely to suffer from cellulitis, abscesses, osteomyelitis, hepatitis B and C, HIV, and endocarditis. In addition, drug users are more likely to suffer from systemic bacterial infections such as tuberculosis and pneumonia. Those who chronically abuse opioids may suffer from bowel issues. Opioid use often leads to constipation and other issues such as bloating, abdominal pain, poor appetite, and ileus (Strain et al., 2020).

Opioid-induced hyperalgesia can result from the chronic use of opioids, a condition where there is an increased sensitivity to pain, which can be severe and chronic. Opioid-induced hyperalgesia typically abates after withdrawal from opioids.

Opioid-associated liver fibrosis is a well-known phenomenon. Research has suggested the liver fibrosis and liver-related morbidity and mortality are associated with heroin use independent of other comorbidities such as hepatitis C, HIV, and other substance use (Strain et al., 2020).

Assessment of Opioid Use Disorder

Screening tools for opioid use include the Rapid Opioid Dependence Screen (RODS) and the OWLS. The RODS is an eight-item tool, and the OWLS is a four-item tool. If the screening is positive, then a complete evaluation using the DSM-5 criteria should be implemented.

A substance use history should include the amount, duration, and frequency of opioid use. When taking a history, it is helpful to determine how much drug is consumed. Users may describe how much drug is being used in a fraction of grams or number of bags. Those with an OUD may use heroin 2-6 times each day (Strain et al., 2020). According to one source, a typical quarter bag has enough heroin to inject several times a day and costs about 25 dollars. Users often use between 20-200 dollars per day (Strain et al., 2020).

Determining when the last use occurred can help evaluate any signs of acute complications from recent drug use, such as any chance for overdose or withdrawal. It is also essential to determine what other drugs are being used, especially benzodiazepines and alcohol, as withdrawal from these agents can be life-threatening. Determine if they have any active-controlled substance prescriptions and the route of ingestion. Opioids are typically injected, taken intranasally, or less commonly smoked.

Part of the assessment is to determine if the patient has been using larger doses over time to determine if tolerance is present as it is one criterion for SUD. Patients with tolerance are more likely to develop withdrawal if they abruptly stop opioids. Many people initially use heroin to get high but then need it to avoid withdrawal.

The assessment should include an evaluation of any occupational, psychological, or social issues from drug use. Determining treatment history helps determine the degree of the OUD. The assessment should include evaluating the type of treatment, including supervised withdrawal, counseling, self-help groups, MAT, residential treatment, or inpatient treatment. Determining the length of the most prolonged abstinence can help predict prognosis, as patients who have had one year of abstinence from heroin predicts a good prognosis (Strain et al., 2020).

The physical examination can detect signs of opioid use and physical consequences of use. Signs of chronic intravenous opioid use include track marks (calluses or scars over subcutaneous veins from repeated injections), and a deviated nasal septum may indicate intranasal drug use. The physical consequence of use may include infections; a heart murmur may suggest subacute bacterial endocarditis, and hepatomegaly may suggest acute hepatitis. Opioid withdrawal may be suggested by yawning, runny nose, muscle twitching, watery eyes, piloerection, and hyperactive bowel sounds.

Laboratory evaluation should include evaluating hepatitis and HIV and a general laboratory evaluation, including a complete blood count and liver and kidney function evaluation. Urine drug tests may be done to look for metabolites of heroin and morphine. Not all substances can be detected if used in the last three days, but chronic users may have a longer detection window. Some opioids are not detected on typical urine drug tests, such as oxycodone, methadone, and buprenorphine.

There are many causes of false positives and false negatives. False positives for amphetamines can occur using pseudoephedrine, phenylephrine, trazodone, bupropion, amantadine, desipramine, and chlorpromazine. False positives for opioids can occur with poppy seeds, fluoroquinolones, quinine/tonic water, and rifampin. More sensitive testing should occur using mass spectrometry, gas chromatography, or liquid chromatography if there is a suspected false positive (Strain et al., 2020).

Alcohol Use Disorder

In the United States, 28 percent of adults have unhealthy alcohol use. Twenty-five percent of those with unhealthy alcohol use have binge drank in the last 30 days. In 2012-2013 it was estimated that 13 percent of adults had alcohol use disorder in the last 12 months (Tice, 2016).

Unhealthy alcohol use is a term that describes the amount of use that is linked to consequences. Risky use is defined as use that increases the risk of health consequences.

Alcohol has a risk threshold, but no other drugs do. The amount of alcohol that is thought to increase health risks is estimated at 14 standard drinks per week or more than four drinks in a day for a man under the age of 65 and seven standard drinks per week or more than three drinks on any day for women and adults over 65. A standard drink is considered 1.5 ounces of hard liquor, five ounces of wine, or 12 ounces of beer (Saitz, 2017).

Specific factors that increase risk should be documented. Factors include any amount of alcohol in those with known liver disease, those who use substances that interact with alcohol, such as benzodiazepines or drug/alcohol use in pregnancy.

All primary care patients should be screened for unhealthy alcohol use annually. Multiple tools are available to detect unhealthy use. A commonly used tool is the AUDIT-C, which is a good screening tool in primary care. If a patient is determined to have moderate to severe alcohol abuse disorder, they should be screened for adverse consequences of use, including medical issues such as cirrhosis (Saitz, 2017).

The AUDIT-C test asks three questions (Bradley et al., 2007):

  • How often do you have a drink containing alcohol?
  • How many drinks containing alcohol do you have on a typical day when you are drinking?
  • How often do you have six or more drinks on one occasion?

Each of the three questions is given a score of zero to four, and the scores are added. A score of 3 or more in women has a 73 percent sensitivity and 91 percent specificity. In comparison, a score of 4 or more in men has an 86 percent sensitivity and 89 percent specificity for alcohol misuse (Saitz, 2020).

The AUDIT screening test consists of 10 questions, takes less than three minutes to perform, and requires scoring. A score of over eight is considered positive for unhealthy alcohol use with an 80 percent specificity and a 90 percent sensitivity (Saitz, 2017).

The CAGE questioner is a four-question screening tool that is often used in primary care. If used as a screening test, one positive response is considered a positive test. For example, two positive questions are 79 percent specific and 77 percent sensitivity for alcohol abuse/dependence, 70 percent specific, and 53 percent sensitive to unhealthy alcohol use. Below are the four questions of the CAGE questioner.

  • Have you ever felt you should Cut down on your drinking?
  • Have people Annoyed you by criticizing your drinking?
  • Have you ever felt bad or Guilty about your drinking?
  • Have you ever taken a drink first thing in the morning (Eye-opener) to steady your nerves or get rid of a hangover?

For those determined to have alcohol use disorder (AUD), brief intervention is used in primary care. For those with mild substance use disorder or unhealthy alcohol use, the goal should be abstinence or reduced substance use. For those with moderate to severe substance use disorder, the goal is to get the patient into more extensive treatment (Saitz, 2017).

Cannabis Use Disorder

According to Gorelick (2021), cannabis is globally the third most commonly used psychoactive substance behind alcohol and tobacco. It is estimated that about approximately 22.2 million people use cannabis each month (CDC, 2017). Delta-9-tetrahydrocannabinol (THC) is the psychoactive component of cannabis. It is estimated that 10 percent of regular cannabis users develop cannabis use disorder (CUD), and one in six will become addicted if use starts before age 18 (CDC, 2017). CUD is associated with psychosis, mood disorder, reduced work/school performance, and cognitive impairment.

CUD presents with at least two manifestations of significant functional impairment or distress over one year. It is classified as mild, moderate, or severe, depending on the present number of symptoms. It presents with a loss of control over its use and continued use despite being aware of the negative consequences (American Psychiatric Association, 2013).

Acute intoxication presents with conjunctival injection, increased heart rate, slurred speech, dry mouth, changes in blood pressure, and ataxia. The patient reports euphoria, sedation, relaxation, increased appetite and may complain of anxiety, memory impairment, concentration difficulty, perceptual disturbances, paranoia, or psychosis. Other adverse effects include chest pain, palpitation, nausea, and vomiting.

Long term effects

  • Cognitive impairment has been noted with regular use, which is typically reversible when cannabis use is stopped.
  • Mood disorders: depression, anxiety, mania.
  • Psychosis and schizophrenia which is more common in those who are starting using in early adolescents.
  • Altered social interaction, interpersonal problems, and impairment in work/school.

The course of cannabis use disorder is variable. Factors that predict CUD include those who also use alcohol and tobacco, co-existent mental health disease, early age of first use, social isolation, friends who also use drugs, quickly transitioning to heavy use, and stressful life events (Gorelick, 2021).

Assessment of Cannabis Use Disorder

A good screening question is asking, "how often did you use cannabis in the last year?" If the patient answer is more than one time, there is a 55 percent positive predictive value and a negative predictive value of 99 percent for detecting CUD (Gorelick, 2020).

Evaluate for signs/symptoms of CUD such as social, academic, or work impairment; or worsening underlying mental health issues. Physical exam findings suggesting CUD includes chronic conjunctival injection, tachycardia, yellowing of the fingertips, and cannabis odor on the clothes. Drug testing is not typically used for screening purposes in primary care but may be used in high-risk populations or places of employment. All positive screening tests should be evaluated further, including screening for other drugs of abuse.

Determining if a patient has mild, moderate, or severe CUD is done for those with a positive screening test. Patients with CUD often deny use when there is reliable/objective evidence that there is ongoing use. If more than two DSM-V criteria are met, the diagnosis of CUD is made. Here is a list of the DSM-V criteria for CUD (American Psychiatric Association, 2013).

  • Taking in larger amounts/longer period than intended
  • Craving
  • Continued use even though problems caused by the use
  • Recurrent use when it is hazardous to so
  • Persistent desire or inability to cut down on the use
  • Failure to fulfill significant life responsibility due to use
  • A large amount of time spent in activities to get, use, or recover from the drug
  • Tolerance
  • Withdrawal
  • Occupational, social or recreational activities given up due to the drug
  • Use despite a physical/psychological problem caused by the use

Evaluation of Addiction

Mental health evaluation is a critical aspect in the management of addiction. A complete mental status exam may be performed, and significant abnormality may suggest possible acute intoxication or severe mental health disease. Therefore, determine mental health/psychiatric diagnosis is a primary step in managing these conditions and improving addiction management. Mental health conditions commonly seen along with substance use disorder include depression, anxiety, bipolar disease, schizophrenia, attention deficit hyperactivity disorder, posttraumatic stress disorder, eating disorders, and personality disorders.

Even though drug/alcohol use can affect any body system, no physical exam finding is specific for a substance use disease. While some, if not most, individuals with a substance use disorder will have no findings on physical exam suggestive of their disease, performing a good history and physical exam may help find complications of drug use.

Physical exam finding that suggests substance use disorder or complications of substance use include:

  • Poor physical hygiene – recent drug use
  • Signs of acute intoxication – unsteady gait, slurred speech, pupil changes, sedation, agitation, conjunctival injection, runny nose, sweating, watery eyes
  • Scars at injection sites (track marks) – suggest intravenous drug use
  • Weight loss – recent heavy drug use
  • Nasal mucosa atrophy or perforation – intranasal drug use
  • Stigmata of liver disease such as spider angioma, palmar erythema, telangiectasias, palmar erythema, gynecomastia, testicular atrophy
  • Elevated blood pressure
  • New heart murmur
  • Other cardiac diseases, including heart failure or cardiomyopathy
  • Abscess – suggestive of methicillin-resistant Staphylococcus aureus
  • Genitourinary abnormalities suggestive of sexually transmitted infection as many individuals with substance use disorder engage in high-risk behaviors
  • Abdominal tenderness/organomegaly – suggestive of hepatitis or pancreatitis
  • Findings of anemia such as fatigue or conjunctival pallor may suggest complications of alcohol use
  • Memory loss suggestive of dementia
  • Pulmonary symptoms such as wheezing or a cough may suggest lung damage from the disease

Assessment should include basic laboratory tests if indicated to evaluate any disease states, but no specific laboratory test is indicated for addiction other than drug testing. The basic drug screens include testing for cocaine, cannabis, amphetamines, some opioids, and phencyclidine. Other drug tests look for synthetic opioids, benzodiazepines, barbiturates, and methamphetamine. Obtaining a drug screen without the patient's permission is a violation of civil rights.

Individuals with a family history of SUD are at higher risk of developing a SUD. Heritability is up to 70 percent for alcohol use disorder, 42-79 percent for cocaine use disorder, and 23 to 54 percent for opioid use disorder (Dugosh & Cacciolo, 2019).

Social history is another important part of the assessment of SUD. Risk factors for SUD include those who have friends with SUD, living environment (e.g., poverty, high violence community), or having a romantic partner with a SUD. In addition, individuals with a SUD often have complicated lives with adverse social events such as violent behavior, financial problems, failure to fulfill social responsibilities, and abnormal social relationships (Dugosh & Cacciolo, 2019).

Diagnosis

When a patient is identified as having unhealthy substance use, an entire substance use assessment should ensue. When substance use risk is high in some situations, it is more appropriate to perform a complete assessment instead of screening, including mental health facilities or correctional settings.

Substance use disorder is a new diagnosis to DSM-V. It is subclassified depending on the type of abused substance (e.g., opioid use disorder). It is defined as substance use with considerable impairment or anguish that presents at least two of the following characteristics over 12 months. (American Psychiatric Association, 2013).

Table 4: Criteria for Substance Use Disorder
  • Tolerance
  • Withdrawal
  • Taking more substance or over a more extended period than anticipated
  • Significant cravings
  • A continual yearning or unsuccessful efforts to reduce/control use
  • Recurrent use in physically unsafe situations
  • Persistent use despite interpersonal or social ill-effects caused by the substance
  • Significant time spent to get, use, or recover from the substance
  • Inability to fulfill significant role obligations
  • Giving up on important social, recreational, or occupational activities due to the substance
  • Persistent use despite having continual/recurrent physical or psychological issues related to the substance use

*No criteria address the amount of use

The severity of the disease is determined by the number of features that are present. When two to three features are present, it is considered a mild disease; if four to five are present, then it is moderate disease, and if six or more are present severe disease is the diagnosis.

Treatment

Detoxification from Opioids

Detoxification, also known as medically supervised opioid withdrawal, is the use of pharmacotherapy to reduce the signs/symptoms of withdrawal in individuals who are using opioids. Detoxification aims to help the patient safely move to continued treatment and maintain abstinence from opioids. Detoxification alone does not lead to abstinence, but it is the first step.

Abstinence requires the patient to address ongoing cravings and many of the psychosocial factors that led to addiction. Addressing the consequences of addiction are another important key factor in the treatment of addiction. Consequences include the addiction's damage to personal relationships, finances, mental/physical health, and employment.

Detoxification is only fully realized when a patient is off all opioids or transitioned to naltrexone. Patients maintained on buprenorphine or methadone are still dependent on opioids.

There are many reasons a person may abruptly stop taking opioids. When opioids are stopped abruptly, detoxification may be done to relieve suffering. Reasons people may stop abruptly include a patient being hospitalized for an acute illness and unable to obtain the illicit opioid, the patient ran out of access to the drug or money to purchase the drug, a person presenting for treatment of OUD, legal issues (e.g., getting incarcerated), the provider who supplied the medication is no longer prescribing the medication or the user wants to stop using the drug.

Pregnant women with OUD should continue MAT with an opioid agonist and not go through medically supervised withdrawal (ACOG, 2019). While it may be done safely during pregnancy, there is a high relapse rate. Relapse can lead to a bevy of problems, including exposure of the baby/mother to drugs, preterm labor, abruptio placentae, fetal growth delay, and even mother/fetal death (Sevarino, 2020). If the mother does not want to use opioid agonists, a slow taper can be performed under medical supervision, which is most safely performed in the second trimester (Sevarino, 2020).

Monitoring patients going through opioid withdrawal should be done with a structured instrument and a thorough physical assessment which will help guide medical management. A standard tool used is the Clinical Opioid Withdrawal Scale (COWS) (Wesson & Ling, 2003). It rates 11 signs/symptoms on a 0 to 5 scale and has a high interrater correlation coefficient (Sevarino, 2020). Testing should be repeated during withdrawal to monitor for progression or improvement.

For individuals with opioid dependence, there are many options. Some suggest the use of buprenorphine over methadone (Sevarino, 2020). Both agents are equivalent efficacious, but methadone is associated with a higher overdose risk, and buprenorphine is easier to prescribe in an outpatient setting (Gowing, 2017). Sevarino (2020) suggests that buprenorphine better manages withdrawal symptoms in detoxification as the taper gets close to the end.

In Kentucky, "buprenorphine may be prescribed for supervised withdrawal or as a maintenance treatment for a patient diagnosed with opioid use disorder" (Kentucky Administrative Regulations, 2021). Buprenorphine should not be prescribed for those with a known hypersensitivity to naloxone or a pregnant patient (unless in consultation with an obstetrician/maternal-fetal medicine specialist who has obtained a DATA 2000 waiver that concludes the benefits outweigh the harms) (Kentucky Administrative Regulations, 2021). Treatment must occur in the APRN's office or another health care facility under supervision. For a patient transitioning from methadone to buprenorphine, treatment is limited to a maximum of one week (Kentucky Administrative Regulations, 2021).

Clonidine or lofexidine can be used in withdrawal but are not as effective as buprenorphine or methadone. Patients treated with opioid agonists are more likely to complete treatment and are less likely to have a positive urine screening after treatment (Gowing, 2017). In addition, methadone was found to be more effective in the management of withdrawal symptoms.

Clonidine and lofexidine are equally effective in managing withdrawal, but lofexidine is approved by the FDA and is better tolerated (Pergolizzi et al., 2019).

Buprenorphine is often used in acute detoxification. Because it has many benefits (Sevarino, 2020):

  • Safer in overdose than methadone
  • The high affinity of the mu-opioid receptor
  • Long duration of action, slow dissociation from the receptor
  • Long duration of action

Caution must be used with buprenorphine as it can bring on or exacerbate withdrawal from opioids. The patients must be in a mild to moderate withdrawal state before taking the first dose of buprenorphine (COWS score of 10-12). The dose will reverse the withdrawal symptoms as it leads to opioid agonism.

Table 5: COWS Scale
The Clinical Opiate Withdrawal Scale (COWS) is an eleven-item scale which a health care provider gives. It evaluates the signs and symptoms of opioid withdrawal. The scores are tallied to help determine the severity of opiate withdrawal and evaluate how dependent the patient is on opioids.

The tool rates each category on a scale from zero to five and looks at clinical features such as heart rate, GI upset, sweating, tremor, restlessness, yawning, pupil size, anxiety or irritability, bone or joint aches, gooseflesh, runny nose, or tearing. The scale can be found here (Nida, n.d.).

While buprenorphine can lead to respiratory depression, it is much less likely to cause this than methadone. It is a partial agonist of the mu-opioid receptors reducing the likelihood of severe respiratory depression. It is more likely to be fatal in overdose if combined with alcohol or benzodiazepines or it is injected.

In most cases, the APRN should recommend an in-office observed induction. However, suppose it is not inducted into the office. In that case, the APRN should document why it was not and implement an appropriate home-based induction as recommended by SAMHSA or the American Society of Addiction Medicine (ASAM). In addition, the utilization of any opioid withdrawal protocol should be documented with a standardized tool (e.g., clinical opioid withdrawal scale) (Kentucky Administrative Regulations, 2021).

The first dose of buprenorphine should not be more than four milligrams. Another dose may follow if symptoms continue, and the dose should not be more than 16 milligrams of buprenorphine on the first day of treatment (Kentucky Administrative Regulations, 2021).

Buprenorphine has effectiveness in medically supervised withdrawal that is similar if not better than methadone and better than clonidine (Sevarino, 2020). Buprenorphine is administered either on an outpatient basis or directly supervised in a clinic. When the dose is administered in a clinic, the first dose, typically 2-4 mg, is given when the patient has a COWS score of 12 or more. The patient typically reports relief within an hour, but some feel better within 10 minutes (Sevarino, 2020). If clinically stable, the patient is observed and then sent home, and the patient is often given a second dose and told to take the medication if needed in six hours or beyond and then come back to the clinic the next day. Patients who require more than 8 mg of buprenorphine are typically better suited for the inpatient setting.

If symptoms are not controlled after the first dose, another 4 mg can be given at one hour, typically resolving symptoms. The patient may then go home. If the patient is given a second dose, another dose is not given to the patient at home. The clinician could consider an alpha-2 adrenergic agonist or other medications to control symptoms.

When the medication is started at home, the patient may enter into mild to moderate withdrawal. At that point, a second dose can be given six or more hours later if symptoms are not controlled.

When to start buprenorphine depends on the half-life of the opioid being abused. Medications with short half-lives (e.g., oxycodone) typically take the first dose of buprenorphine 6-12 hours after stopping the opioid. For those on methadone, buprenorphine should be given about 36 hours after the last dose, and before switching, the dose should be weaned to 30 mg/day (Sevarino, 2020).

If withdrawal symptoms worsen after the first dose, the next dose (if on short-acting opioids) or until the following day (if long-acting opioids) should be held. The patient should be treated with clonidine and adjunctive medications to treat other symptoms such as anxiety, insomnia, abdominal cramping, nausea, diarrhea, or muscle spasms.

Treating acute withdrawal typically lasts 5-10 days, but longer tapers have improved symptom control. Longer tapers have been shown to reduce drug relapses and improve the effectiveness of treatment (Sevarino, 2020).

After the first day, that goal is to stabilize the patient and minimize withdrawal symptoms. A similar total dose is given to the patient on the second day in one dose, commonly 8 mg. For patients with continued withdrawal symptoms, the dose can be raised by 4 mg (Sevarino, 2020). Those who have significant cravings and withdrawal symptoms on day three typically do not have successful detoxifications, and other options may need to be considered (Sevarino, 2020).

After 24 hours of controlled withdrawal symptoms, the buprenorphine can be tapered. Due to its long duration of action, the taper can occur rapidly. For individuals on 12 mg, a tapering of 2 mg a day can occur, and if on 16 mg the first day, the dose can be reduced by 4 mg and then 2 mg a day. Sometimes withdrawal symptoms occur at lower doses. At that point, the dose may be maintained, adjunctive medications may be used, or if the patient is receiving a home-based taper, then moving the patient to an office-based taper may occur (Sevarino, 2020).

Methadone can also be used for detoxification. It does have some concern for overdose and must be supplied in a supervised setting. The dosing has the goal of controlling withdrawal symptoms and avoiding oversedation. An initial dose of 10 to 20 mg is given with a maximum dose of 30 to 40 mg over the first 24 hours. There are varying dosing programs, but typically durations include at least 14 days for outpatient and five days for inpatient treatment (Sevarino, 2020).

The dose on day 2 is dependent on the clinical status of the patient. A taper of the methadone can be started after day two and can be tapered over one week or more. After a taper occurs, relapse is a concern, and maintenance doses should be considered.

Alpha-2 adrenergic agonists can significantly reduce signs and symptoms of withdrawal. Common agents in this class include lofexidine and clonidine. They help treat the symptoms of diarrhea, nausea, abdominal cramping, sweating, irritability, and anxiety and are less effective for insomnia, cravings, and muscle aches. These agents are not typically used as primary agents in opioid withdrawal in favor of buprenorphine or methadone. They are often used as adjunctive treatments to help manage symptoms (Gowing et al., 2016).

In settings where opioids are prohibited (such as prisons), alpha-2 adrenergic agonists are often used as a first-line agent. These agents are very sedating and sometimes abused for this purpose, but the risk is low. In addition, these medications reduce anxiety by lowering noradrenaline levels and reduce withdrawal symptoms by reducing hyperactivity in the locus coeruleus (Sevarino, 2020).

Pregnancy, hypotension, psychosis, renal insufficiency, and cardiac instability are contraindications to the use of alpha-2 adrenergic agonists. Side effects include sedation, dry mouth, constipation, and hypotension. Therefore, Alpha-2 adrenergic agonists should not be mixed with tricyclic antidepressants.

Clonidine is dosed at 0.1, 0.2, or 0.3 mg two times a day. Symptom relief is typically noted within 30 minutes. The patch is used in some settings, but effects are not noted for three days as it takes a while for blood levels to become adequate with the patch.

One strategy for dosing for the first day is giving 0.1-0.2 mg of the dose (higher dose for patients over 200 pounds) if the blood pressure is 90/60 mm Hg or higher and a heart rate greater than 60 beats/minute. Vital signs are rechecked in 45-60 minutes and if the blood pressure and heart rate do not drop below the above levels and symptoms are still present, then another 0.1 mg dose can be repeated every 45-60 minutes for up to four doses (Sevarino, 2020). For uncontrolled symptoms changing to buprenorphine-naloxone or methadone may be considered.

For the second to the fourth day, the patient can receive the same total dose as the first day, dived three or four times a day. Finally, on day five tapering begins, by reducing the dose by 0.1 to 0.2 mg a day; if tapering is done too fast, rebound hypertension may occur. Clonidine can also be used as an adjunct to withdrawal with buprenorphine or methadone.

Adjunctive Medication

Withdrawal can bring a bevy of other symptoms such as nausea, diarrhea, abdominal cramping, myalgia, anxiety, restlessness, and insomnia. Medications can be given to manage these symptoms. Adjunctive treatment is more frequently used in those on alpha-2 adrenergic agonists but can be used with buprenorphine.

Here are some adjunctive treatments used (many of them are used off label):

  • Anxiety, irritability, and restlessness can be managed with hydroxyzine, diphenhydramine, or benzodiazepines (which should only be considered in an inpatient setting due to respiratory depression with opioids).
  • Insomnia can be managed with mirtazapine, doxepin, zolpidem or trazodone.
  • Diarrhea can be managed with loperamide or bismuth.
  • Nausea and vomiting can be managed with promethazine, prochlorperazine, or ondansetron.
  • Abdominal cramping can be managed with dicyclomine.
  • Muscle pain can be managed with acetaminophen or non-steroidal anti-inflammatories.
  • Muscle spasms can be managed with muscle relaxers or diazepam; these agents may cause sedation, especially when combined with methadone/buprenorphine (Seravino, 2020).

Other less commonly used withdrawal methods include naltrexone-accelerated withdrawal, ultra-rapid or anesthesia-assisted opioid withdrawal, acupuncture, and extended-release tramadol.

Quick withdrawal, often seen when precipitated by naltrexone or buprenorphine, may be more severe and lead to more severe complications such as stress cardiomyopathy or delusions (Sevarino, 2020). These complications can also occur in an unassisted detoxification withdrawal. Other complications include suicide, dehydration (often caused by insufficient oral intake), and electrolyte abnormalities. Another complication is opioid overdose. If the patient abandons treatment and uses his typical dose of opioids with a reduced tolerance, an overdose may occur.

After medical detoxification, relapse rates are high. Therefore, continued treatment is a critical step to prevent patients from going back to their old lifestyle. Treatment after detoxification includes psychosocial interventions, pharmacotherapy, clinical monitoring, education, and take-home naloxone.

Treatment of Opioid Use Disorder

It is recommended to monitor progress during OUD treatment. Features of a monitoring program include urine drug screening, treatment attendance, and many brief instruments (Dugosh & Cacciolo, 2019).

Individuals with OUD are likely to relapse after withdrawal, especially in the absence of a maintenance treatment program. The use of opioid agonists significantly reduces the risk of relapse.

Pharmacotherapy combined with psychosocial treatment is often used long-term to prevent relapse of OUD. Pharmacotherapy typically consists of an opioid agonist (methadone or buprenorphine) or an opioid antagonist (naltrexone). Before prescribing medications, it is essential to determine if the patient is physiologically addicted; and if so, medically supervised withdrawal may be necessary before starting naltrexone.

A non-pregnant adult who is not addicted to opioids is a candidate for addiction counseling and possibly long-acting injectable naltrexone. For the adult who is physically dependent but is post-withdrawal, long-acting injectable naltrexone may also be considered. Before starting naltrexone, withdrawal must be complete. However, withdrawal does not have to be complete before starting methadone or buprenorphine. Naltrexone is typically used by a highly motivated patient and has mild opioid use disorder (Saxon & Strain, 2019).

MAT is first-line treatment instead of psychosocial treatment alone when the patient suffers from moderate to severe opioid use disorder. In moderate to severe use disorder, the use of buprenorphine is the preferred agent. Research suggests that methadone has a better capacity to prevent relapse but is more dangerous as it has a high risk of overdose (Saxon & Strain, 2019).

Psychosocial treatment alone can be used in a handful of conditions.

  • The patient had a sustained prior response to psychosocial treatment
  • The patient has a strong preference for psychosocial treatment despite education regarding MAT
  • The patient has mild disease, is very motivated, and has good premorbid function and a robust social support network

Shared decision-making is a crucial aspect in determining which is the best treatment option to maintain. First, a discussion regarding the risks and benefits of each treatment option should be laid out to the patient, and then a shared decision about the best treatment option should be made. Shared decision-making has been shown to improve outcomes in SUD treatment at one year.

Withdrawal treatment, also known as detoxification, lowers the risk of withdrawal symptoms. It should not be used as a stand-alone treatment but combined MAT and psychosocial treatment to prevent relapse.

The use of medication-assisted treatment MAT is considered the first-line treatment for opioid use disorder. Treatment can help patients get their life back and become productive members of society.

MAT may per done with opioid agonists (methadone), partial opioid agonists (buprenorphine), or an opioid antagonist (naltrexone). Opioid agonists squelch cravings and withdrawal as well as block the effects of other opioids.

When opioid agonists are used, patients are physically dependent on methadone or buprenorphine. Still, these patients do not have the negative behaviors associated with dependence/addiction to other opioids, including heroin (Strain, 2019).

Patients often remain on MAT with opioid agonists for years. Some patients are tapered off, and those with OUD who have the most success with a tapering have no significant alcohol use, no illicit drug use, and have a good social support network. Tapering off medication should only be done by a clinician with expertise with weaning and should be done very slowly, often over the years. Opioid agonists are associated with a reduced mortality rate (including all-cause mortality and death due to drug use) in those with a known OUD (Strain, 2019).

Non-pharmacological Therapy

Psychotherapies are often used in the management of addiction. Cognitive-behavioral therapy (CBT) is a commonly used modality. CBT attempts to change faulty thought processes and attributions associated with substance use and change behaviors that increase the risk of substance use. CBT has positively affected substance use outcomes compared to other interventions (Peavy, 2021).

CBT is meant to help patients understand their thought processes, understand their risk factors, improve their ability to address problems, and develop coping skills. First, the patient with OUD must identify behaviors and thought patterns that put them at risk to use and determine when they will occur. Then, once these thought patterns and behaviors are identified, the patient must be able to develop coping resources.

Problematic drug use is considered a learned behavior, although genetics and other biological factors play a role. In stressful situations, some people are more likely to engage in substance use. The use of CBT can help people manage stressful situations and theoretically reduce cravings and subsequent substance use. CBT works to enhance the individuals coping abilities with stress and enhance their motivation for behavior change to reduce drug use (McKay, 2020).

Specific thought patterns that increase the risk of substance use include those who strongly believe that other people influence their action, believing one slip up will lead to a full-blown relapse, and individuals who notice substance-related cues in the environment (such as seeing people using drugs or an ad for alcohol) are more likely to use (Peavy, 2021).

Parts of CBT for OUD include psychoeducation, helping patients develop coping and problem-solving skills, analyzing the patient's substance use, helping patients develop good interpersonal skills, and encouraging recovery-based activities such as encouraging employment, participation in self-help groups, and participating in activities that improve mood. Developing skills for CBT can be attained by clinicians through the utilization of education classes and resources such as manuals that teach CBT

Other skills that can be developed in CBT include communication skills, improving motivation, drug refusal skills, receiving criticism, taking and giving compliments, coping with depression, coping the anger, managing stress, dealing with interpersonal problems, and increasing pleasurable activities (Peavy, 2021). In addition, factors that increase the change of relapse need to be identified and addressed.

Patients are often given homework assignments between CBT sessions to help reinforce principles. The assignments may focus on self-monitoring of disease such as cravings and exposure to risky situations or cues linked to substance use, such as ads for alcohol. The homework may involve rehearsing coping responses. Behavioral couples therapy uses CBT to work with individuals in committed relationships where one person has an OUD, and the other does not.

In addition to CBT, addiction counseling, behavioral, medical management, mutual help groups, and motivational interviewing can all be used to manage OUD and SUD.

Addiction counseling is often used in drug and alcohol use disorder and can be done in group settings or individually. It includes education and a variety of psychotherapies. Other key components are based on the principle of 12-step programs, helping patients avoid risky situations, encouraging self-help groups, and encouraging healthy social activities. Critical components to addiction counseling include adoption of the 12-step belief, addressing any ambivalence the patient has, focusing on the present, planning of free time, setting a goal of abstinence, avoiding individuals and situations that are associated with use, participation in drug counseling, self-help groups, managing anger, addressing guilt/shame over previous use, employment services, managing money and focusing on short term behavioral goals (McKay, 2020).

Addiction counselors may get frequent urine samples for drug testing. The patient should also be asked about drug use. If any drug use is identified, evaluate the precipitating factors and strategies to avoid drug use in the future.

Behavioral, medical management offers specific interventions for those receiving MAT for opioid addiction. It includes educating patients about substance use disorder and its treatment, monitoring the patient’s drug and alcohol use, monitoring symptoms and progress, monitoring medication adherence, monitoring for side effects of medication, and encouraging mutual health groups. Behavioral, medical management is effective in SUD and reduces use (McKay, 2020)).

Twelve-step programs encourage the use of mutual health groups that include Alcoholics Anonymous and Narcotic Anonymous. However, some people prefer CBT to a 12-step program, including individuals who dislike the group setting or the spiritual aspect of the 12-step program.

Utilizing the community reinforcement approach looks to help those with OUD maintain sobriety by providing intervention to help the patient function better. It includes employment counseling, fostering healthy social networks, and helping patients access social services.

Mutual help groups are effective in the treatment of OUD. Increasing participation can be accomplished by education, helping patients find meetings, working with patients through the first few steps, and linking patients to program participants.

Methadone

Methadone is a schedule II drug, and only licensed hospital units/opioid treatment programs can use methadone for OUD or treatment of withdrawal. There are a couple of exceptions to this rule, and federal guidelines are in place to determine who is eligible for methadone in the United States (The Substance Abuse and Mental Health Services Administration, 2019)

Methadone works by binding to the mu-opioid receptor, and its duration of action is 1-2 days. It lowers cravings for opioids, prevents withdrawal, and reduces euphoria if opioids are used. One study showed that those on 50 mg of methadone had reduced rates of opioid use, as evidence by reduced positive urine samples for opioids. In addition to reducing opioid use and mortality, methadone use has been found to reduce criminal behavior and spread the human immunodeficiency virus (Strain, 2019).

Side effects of methadone include sweating, edema, constipation, drowsiness, and possibly erectile dysfunction. In addition, some patients on chronic methadone develop hyperalgesia within the first months of therapy (Strain, 2019).

Methadone may be associated with QT prolongation and torsade de pointes (Strain, 2019). It is unclear if getting a baseline EKG before starting methadone is warranted. Some suggest an EKG should be done on those with a personal or family history of prolonged QTc interval, structural heart disease, history of arrhythmia, cardiac risk factors, or being on other medications that prolong the QT interval (Strain, 2019). Naltrexone or buprenorphine should be considered instead of methadone when there is a prolongation of the QTc. When the QTc is longer than 500 msec, strong consideration should be given to stopping or possibly reducing the methadone dose.

Overdose death is one risk with methadone, and those taking benzodiazepines at the same time are at increased risk of overdose. Therefore, methadone has a higher risk of overdose than buprenorphine, and all patients who have OUD should be educated about overdose and should be given naloxone.

Methadone has multiple drug-to-drug interactions, so extreme caution should be used with methadone in individuals on other medications.

Methadone is typically dosed once a day, but some use twice a day dosing in particular situations. Twenty to 30 mg is typically the dose given on the first day of treatment. After that, increase dosage in 5 to 10 mg increments no faster than every 2-3 days. Methadone is typically given in liquid form, but it is also available in tablet form. Dosing can be variable, and 20 to 30 mg may be enough to prevent withdrawal but not enough to stop craving or block the euphoria from other opioids. Dosing is different for OUD when compared to pain management. The target dose is often 60-80 mg a day. If higher doses are needed to suppress cravings, titration is much slower than this level. Some research suggests that patients with OUD are more effectively managed on doses of 80-100 mg than lower doses (Strain, 2019).

Medications are administered in licensed centers, and observation of taking the medication occurs. Occasionally, patients can take medication home, but those eligible for this should be low risk and chosen carefully.

Both methadone and buprenorphine can be used in pregnancy, and they reduce the risk of the pregnant patient using illicit opioids. In those with OUD, these medications increase the woman’s ability to be involved with their prenatal care and reduce the risk of illicit drug use (Strain, 2019). In addition, even though a small amount of methadone is secreted in breast milk, breastfeeding is recommended in the woman on methadone if she is not using other drugs and is HIV negative (Strain, 2019).

Not enough data is available for naltrexone to be recommended in pregnancy, and there is the risk of the mother and fetus being physiologically stressed by withdrawal (Rodriguez & Klie, 2019).

Buprenorphine

Buprenorphine is a partial opioid agonist, and while it is associated with respiratory depression and euphoria, these effects are considerably weaker than full opioid agonists. It is associated with a lower level of misuse, reduces cravings and withdrawal, and is safer in overdose.

Buprenorphine is a schedule III-controlled substance and can be dispensed in a licensed opioid treatment program or an office-based practice. Advanced Practice Registered Nurses (APRN) are being called on to participate in patient care with addiction disorders. In Kentucky, according to KAR 20:065, "Buprenorphine" means the controlled substances Buprenorphine-Mono-Product and Buprenorphine-Combined-with-Naloxone(Kentucky Administrative Regulations, 2021).

To prescribe buprenorphine in Kentucky, the APRN should (Kentucky Administrative Regulations, 2021):

  • Be Drug Enforcement Agency (DEA) registered to prescribe the medication
  • Present a copy of the DEA Controlled Substance Registration Certificate to the Board of Nursing
  • Have completed medication-assisted treatment (MAT) education through a course sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA)
  • Follow all federal statutes and regulations relating to the prescribing of buprenorphine.
    • The maximum number of patients allowed to be seen by the APRN annually
    • Placing the special DEA identification number and the regular DEA registration number on all prescriptions written for opioid dependence
  • Obtain a DATA 2000 waiver as an APRN; without a DATA 2000 waiver, the APRN cannot perform a focused examination necessary to prescribe buprenorphine for those with substance use disorders
  • Comply with all federal statutes and regulations relating to the prescription of controlled substances via telehealth for MAT for opioid use disorder
  • APRNs in the United States who practice telemedicine (in accordance with 21 U.S.C. § 802(54)) do not have to perform an in-person evaluation before prescribing/dispensing controlled substances via the internet

Buprenorphine is a partial mu-opioid agonist and has fewer restrictions when compared to methadone. It comes in multiple formulations, including an injection, implant, and transmucosal form. The transmucosal form is often combined with naloxone (even though naloxone has poor bioavailability, sublingually). The addition of naltrexone reduces the risk of abusing the buprenorphine. By adding naloxone to buprenorphine, it causes withdrawal symptoms if the medication is dissolved and injected. In addition, naloxone prevents other opioids from causing euphoric effects.

Side effects of buprenorphine include insomnia, dry mouth, dizziness, tremors, palpitations, constipation, nausea, vomiting, headache, fatigue, myalgia, fever, sweating, blurry vision, and dilated pupils. More severe side effects include overdose, respiratory depression, dependence, withdrawal, and adrenal insufficiency. Buprenorphine-naloxone should not be used in severe liver impairment. It has a lower risk for lethal overdose when compared to methadone. Overdose risk is highest in individuals who use buprenorphine with alcohol or benzodiazepines. Buprenorphine has proven to be effective in the management of opioid use disorder. Mortality rates are reduced in OUD when patients are treated with buprenorphine-naloxone compared to being off the medication. In addition to overall death rates, mortality was reduced due to reduced drug use and accidental poisoning. The same study showed that mortality rates were lower on buprenorphine-naloxone when compared to methadone (Pearce et al., 2020).

When starting buprenorphine, the buprenorphine-naloxone combination is generally recommended (Strain, 2019). The patient should be abstinent from opioids for a period to be in a state of mild/moderate withdrawal. During withdrawal, buprenorphine will alleviate the symptoms of withdrawal.

Before starting buprenorphine, the patient must refrain from opioids for at minimum 12-24 hours and be in the initial stages of opioid withdrawal. If a patient is given buprenorphine when there are opioids in the system or the patient is not in the early stages of withdrawal, an acute withdrawal state may ensue.

Before buprenorphine is prescribed for OUD or supervised withdrawal, the APRN must thoroughly evaluate the patient and the patient’s record. The evaluation should include the patient’s history of present illness (HPI), history of drug use, social and family history, medical/psychiatric history, a physical exam, and laboratory testing. Part of the evaluation should be obtaining prior medical records for evaluation and discussing and documenting prior treatments.

Appropriate laboratory tests include a drug screen, liver function tests (LFTs), metabolic panel, complete blood count (CBC), HIV screening, and hepatitis serology. In addition, an evaluation by a mental health care provider with expertise in addiction should ensue.

The APRN should review the prescription drug monitoring program (PDMP) and obtain a report if the patient has been prescribed a controlled substance in the last 12 months.

Buprenorphine should not be used with other opioids, stimulants, benzodiazepines, or other sedative-hypnotics unless there is consultation with a certified physician in psychiatry or addiction medicine; an APRN certified in addiction therapy or a psychiatric-mental health nurse practitioner. For no more than 30 days, an APRN may prescribe buprenorphine, without consultation, to an induvial who is also on another opioid, stimulant, benzodiazepine, or other sedative-hypnotics when the provider is addressing a “documented extraordinary and acute medical need” (Kentucky Administrative Regulations, 2021).

The APRN should have a conversation with the patient and discuss alternative treatment options. In addition, the APRN should discuss the risks and benefits of treatment with buprenorphine. Before treatment, informed consent should be obtained. The treatment plan should include an evaluation by a mental health professional with addiction expertise and should also include a twelve-step program or mental health counseling during treatment. Compliance with the mental health professional recommendations should be documented within 90 days of starting treatment (Kentucky Administrative Regulations, 2021).

The starting dose for buprenorphine-naloxone is typically 4mg/1mg. Two hours after the dose was given, if the patient is still having withdrawal, 2 to 4 mg of buprenorphine-naloxone can be taken. The next day the patient gets one dose with the exact total dosing he/she took the day before. If any withdrawal symptoms are noted, the dose may be increased to a maximum of 16 mg of buprenorphine in 4 mg steps. Eight to 16 mg will stabilize most patients, but responses are variable, and a few may need up to 32 mg/day (Strain, 2021).

If the APRN prescribes the medication and is not certified in addiction therapy and the dose of buprenorphine exceeds 16 milligrams per day, then the patient should be referred. The referral should go to a psychiatrist, addiction medicine specialist, an APRN certified in addiction therapy, or a psychiatric-mental health nurse practitioner. The consult should determine if the current dose is appropriate and continued treatment (Kentucky Administrative Regulations, 2021).

Some suggest the use of buprenorphine over methadone in moderate to severe OUD as it is less lethal. However, methadone should be considered in those with misused buprenorphine, who had an inadequate response with buprenorphine, those with high levels of opioid dependence, and those who prefer methadone due to previous success (Strain, 2021).

It is difficult to get through the opioid withdrawal, and therefore opioid agonists (instead of antagonists) can manage symptoms of opioid withdrawal (Lee et al., 2018). If a complete withdrawal can be accomplished, then the effectiveness of a long-acting agent such as naltrexone has similar outcomes to buprenorphine (Lee et al., 2018). Research has shown little difference in abstinence rates between daily transmucosal buprenorphine and long-acting injectable naltrexone, but stabilization was easier on the buprenorphine (Tanum et al., 2017).

In a study, 570 people with OUD were given an injection of long-acting naltrexone or daily transmucosal buprenorphine for 24 weeks. The study concluded that buprenorphine was 94 percent successful in inducing (moving the user from an abused opioid to a dose of buprenorphine which will offer relief from withdrawal), and the naltrexone induced only 72 percent. In addition, those assigned to naltrexone were more likely to relapse when compared to those on buprenorphine. However, there was no significant difference in relapse when comparing naltrexone and buprenorphine in those who were successfully induced onto their respective medications, with rates for both groups being slightly above 50 percent (Lee et al., 2018).

Buprenorphine is preferred over methadone as it is safer, although some evidence suggests that methadone is slightly more effective (Saxon & Strain, 2019). A meta-analysis of 11 studies concluded that methadone and buprenorphine effectively manage OUD, but methadone is more effective in keeping patients in treatment (Strain, 2019).

The risk of overdose is much more significant with methadone when compared to buprenorphine. Methadone is much more challenging to use as it requires daily clinic monitoring, and it may lead to an increased risk of respiratory depression and lethal overdose. As a partial opioid agonist, buprenorphine is much less likely to cause respiratory depression. Methadone is associated with a fourfold greater mortality rate from overdose than buprenorphine. All patients who are prescribed either methadone or buprenorphine must be educated regarding overdose.

Less research is available regarding treatment efficacy on mild OUD than moderate to severe OUD. Naltrexone is often recommended for mild OUD. It blocks the mu-opioid receptor, so if a patient takes another opioid, there will be no euphoria. It is also not associated with withdrawal if stopped. Unlike methadone and buprenorphine, it does not lead to physiological dependence. It is easier to switch from naltrexone to methadone or buprenorphine but switching from buprenorphine or methadone to naltrexone requires up to 10 days to withdraw from the medication.

Specific interventions may be helpful in certain situations. For example, those who continue to use opioids or do not patriciate in treatment may benefit from motivational interviewing. In addition, nonadherence can be remedied by the supervised taking of the medication or using long-acting injections of naltrexone or buprenorphine. Long-acting formulations of naltrexone are more effective than oral agents in reducing heroin use and reducing heroin relapse (Saxon & Strain, 2019).

Certain situations do not allow the use of controlled substances. For example, individuals who transport hazardous material, health care workers, and commercially licensed drivers are sometimes not allowed to use methadone or buprenorphine. In addition, incarcerated individuals are generally not allowed to utilize these agents.

Pregnancy increases the risk of certain medications. Research suggests that buprenorphine and methadone are not teratogenic (Zedler et al., 2016). The use of buprenorphine is less likely to cause a fatal overdose when compared to methadone. The use of naltrexone in pregnancy is not considered a first-line treatment as it lacks good clinical data that shows its safety and effectiveness. In addition, there are concerns about the stresses of withdrawal on the mother and fetus (Rodriguez & Klie, 2019). Observational studies show that outcomes are not significantly different between buprenorphine or methadone versus naltrexone in managing pregnant women (Saxon & Strain, 2019). While methadone has been the treatment of choice in pregnant women with OUD, mainly due to years of experience, buprenorphine is adequate and safe. Compared to methadone, it has a lower rate of neonatal abstinence syndrome (Strain, 2019).

Females of childbearing age should have a pregnancy test. If the test is positive, then the patient should be counseled regarding the risk of neonatal abstinence syndrome. In addition, before buprenorphine is prescribed to a pregnant or breastfeeding patient, the APRN should consult with a maternal-fetal medical specialist or obstetrician who has a DATA 2000 waiver to determine if benefits outweigh the risks (Kentucky Administrative Regulations, 2021).

When a patient is hospitalized and is currently being treated with methadone or buprenorphine, treatment should continue. Ideally, the hospital should contact the prescriber or check the state prescription monitoring program to determine the appropriate dose. Thirty milligrams of methadone may be prescribed for those in whom the dose cannot be verified. That dose is enough to prevent an acute withdrawal. When using buprenorphine, the buprenorphine dose the patient states they take should be used; respiratory depression is uncommon with buprenorphine.

Patients on MAT should be involved in some sort of psychosocial treatment. Common interventions include group or individual counseling, a mutual-help group such as a 12-step program, cognitive behavioral therapy, emotional interviewing, behavioral drug counseling, and acceptance and commitment therapy.

Psychosocial treatment alone is inferior to MAT therapy and is not recommended in OUD as first-line treatment (Saxon & Strain, 2019). In addition, it is unclear which psychosocial interventions are most effective in managing OUD. One approach involves using weekly addiction counseling, help groups several times per week, and another method that has proven efficacy, such as CBT, motivational interviewing reinforcement approach, contingency management, or community reinforcement programs (Saxon & Strain, 2019).

Appropriate interventions can be implemented by determining the patient’s readiness to change. Those who are in the pre-contemplation or contemplation stages should be managed with motivational interviewing to encourage change. Those in the action stage may be better suited to CBT, which provides steps to move them toward their goals.

How long can one remain on MAT? No guidelines definitively define this question. Patients who have a good response may remain on MAT indefinitely. It is reasonable to taper the medication for those who are doing well for 6-12 months, as evidence by not using, is productive, not engaged in criminal activity, and has stable interpersonal relationships. If the patient becomes unstable during the taper, the taper should be halted. For patients on naltrexone, the medication can be abruptly stopped. The patient should be monitored closely for any indications of relapse and started back on treatment if they occur. (Saxon & Strain, 2019).

Limited data is available to help clinicians whose patients had an inadequate response to opioid use disorder treatment. For patients who had an unsuccessful response to an opioid agonist, utilization of the other opioid agonist could be considered. For example, if a patient has an unsuccessful response to transmucosal buprenorphine, switching to a long-acting injection of buprenorphine can be considered. When taking buprenorphine and an inadequate response is obtained, one could consider a switch to methadone. When methadone is used as the first agent and the patient has an inadequate response, it is a little more complicated to switch to buprenorphine. The patient may need to be off methadone for a few days, so there is no precipitated withdrawal when starting the buprenorphine.

Patients who continue to use opioids despite treatment with opioid agonists could be considered for naltrexone injection if they can tolerate a supervised withdrawal from the opioid. For patients who do not respond to oral naltrexone, the use of a long-acting injection of naltrexone could be considered. Intensifying psychosocial therapies should also be considered.

Here is a list of buprenorphine products used for OUD that the FDA approved.

  • Generic Buprenorphine/naloxone sublingual tablets
  • Buprenorphine/naloxone sublingual films (Suboxone®)
  • Buprenorphine/naloxone sublingual tablets (Zubsolv®)
  • Buprenorphine sublingual tablets (Subutex®)
  • Buprenorphine extended-release injection (Sublocade®)
  • Buprenorphine/naloxone buccal film (Bunavail®)
  • Buprenorphine implants (Probuphine®)

Key points of patient education with buprenorphine include:

  • Tell your prescriber if you are planning to become pregnant
  • Discuss other medications taken with your prescriber; there are a lot of potential interactions
  • Avoid using alcohol, sedatives, other opioids, tranquilizers, or illegal drugs with buprenorphine
  • Keep medication stored safely
  • Do not share medication

Buprenorphine has misuse potential, and the addition of naloxone to buprenorphine reduces its chance of being abused. For patients who have issues with misuse, diversion, or adherence issues, the use of implanted or injected buprenorphine has benefits over the transmucosal formulations. The implanted version of buprenorphine was approved in 2016 and provided six months of medication. Those stabilized on a buccal or sublingual formulation of 8 mg or less are candidates for implanted buprenorphine (Strain, 2019). A surgical procedure is needed to insert and remove the device. The implanted device may be used two times for 12 months (Strain, 2019). The implant is associated with reduced rates of positive urine drug tests compared to placebo.

Injectable buprenorphine came to market in 2018. Buprenorphine XR is approved for use after at least one week of clinical stabilization with transmucosal buprenorphine and is dosed monthly. It is dosed 300 mg in the first two months and then 100 mg monthly after that. Some patients may receive 300 mg monthly maintenance doses (e.g., patients not adequately managed on 100 mg per month). A longer duration of treatment (12 months) is associated with a better chance of abstinence, a better mood, quality of life scores, pain, and improved employment rates (Ling et al., 2020). In addition, the injection formulation is known to be more effective than placebo in those with severe opioid use disorder (Haight et al., 2019).

The most severe side effect is death by overdose, but overdose rates are less than methadone (Strain, 2019). All-cause mortality rates for those on buprenorphine is 4.3 per 1000 person-years when patients are in treatment and 9.5 per 1000 person-years when patients are out of treatment (Sordo et al., 2017).

Many people are maintained on buprenorphine indefinitely, but some are weaned. If weaning is to occur, it should be tapered gradually. Reducing the dose by 2 mg every 7 to 14 days is one strategy (Strain, 2019). More rapid tapers may be done but are not as effective. Some individuals who need to be rapidly weaned can have the dose reduced by 2 mg every one to three days (Strain, 2019).

Patients who are placed on buprenorphine after being on methadone may have withdrawal symptoms (Strain, 2019). Therefore, methadone should be reduced to less than 30 mg before starting buprenorphine to reduce the risk of withdrawal.

Buprenorphine in Kentucky (Rules from 201 KAR 20:065)

When a patient presents to the APRN after seeing another provider and the patient has withdrawn in the absence of relapse previously, the provider should document a history of withdrawal, teach the patient about possible withdrawal, and continue maintenance treatment at the same or a lower dose than the previous provider. In addition, the APRN should see the patient at the same frequency or more often than the previous provider was seeing the patient. After the initial prescription, APRN 201 KAR 20:065 recommends that the amount of buprenorphine prescribed should be enough to minimize cravings and opiate withdrawal, be enough to get the patient to the next visit, not above the FDA approval limit and not produce significant sedation (Kentucky Administrative Regulations, 2021).

After the initial prescription of buprenorphine, the APRN should see the patient within ten days and then no longer than ten-day intervals for the first month. For the second month after induction, the patient should be seen at intervals of no more than 14 days (Kentucky Administrative Regulations, 2021).

After two years of treatment, if it is deemed that the patient has objective signs of treatment success, the patient may be seen once every three months. At this point, the APRN should assess and document if the dose should be continued or modified. If there is evidence of non-compliance, the patient should be seen more often. If a patient must miss an appointment, the APRN should “make best efforts to see the patient as soon as possible and document the circumstances in the patient’s chart” (Kentucky Administrative Regulations, 2021).

At these visits, the APRN should collect data to incorporate into the treatment plan to support the maintenance of the plan or modification of the plan. The treatment plan should be based on a complete assessment including:

  • Reviewing compliance with the treatment plan
  • Reviewing KASPER or other PDMP
  • Ordering and reviewing drug screens

The APRN may adjust the dose of the medication, wean the medication, modify the frequency of the visits or obtain a consultation with a specialist.

At least eight drug screens should occur every twelve months. The patient should be screened for buprenorphine, methadone, alcohol, opioids, benzodiazepines, THC, amphetamines, gabapentin, and cocaine. Two of the drug screens should be random, and a pill count should coincide. At least one of these two drug screens should be confirmed by gas or liquid chromatography/mass spectrometry. A positive drug screen should be incorporated into the decision to continue or modify treatment (Kentucky Administrative Regulations, 2021).

Lost or stolen medication should not be routinely refilled. In the case when medication is lost or stolen, the automatic refill is not appropriate. Instead, the patient should be individually assessed and consider any prior episodes of the patient losing the medication or getting the medication stolen.

After the patient is started on buprenorphine, the patient should have a treatment plan that necessitates objective behavioral modification, including a twelve-step program or mental health counseling. The patient should also have a mental health evaluation by a provider with expertise in addiction within 90 days of starting treatment. The patient needs to observe the recommendations set forth by the mental health provider (Kentucky Administrative Regulations, 2021).

The APRN who is appropriately credentialed (has a DEA waiver/registration to prescribe buprenorphine) must get four annual hours of training in addiction disorders, including 1.5 contract hours of pharmacology.

Emergency Use of Buprenorphine

An APRN may initiate buprenorphine in an emergency (emergency department, urgent care setting) or when a patient is an inpatient with opioid use disorder without meeting the above criteria. Before prescribing, the APRN must ensure that there is no harmful interaction with another medication. Medications that may interact include benzodiazepines, sedative-hypnotics, carisoprodol, or tramadol. Informed consent must be obtained before starting treatment, and written instructions for follow-up care must be given. Instructions may include referral or recommendations to outpatient providers, bridge providers, and residential treatment programs. The induction dose must be observed with the first dose not exceeding four milligrams of buprenorphine, followed by further doses, but no more than 24 mg.

Opioid Antagonists

Naltrexone blocks the euphoric effects of opioids. The patient should not be withdrawing when the medication is started, as it may cause the patient to go into more severe withdrawal. When starting naltrexone, it should be medically supervised to assess for withdrawal.

Naltrexone is given as a daily pill or a monthly injection. Oral naltrexone is started at 25 mg per day for 2-3 days and then increased to 50 mg per day. The medication should not be started until at least one week after the last time an opiate was taken. In some situations, a naloxone challenge test (Table 6) can ensure the safety of starting the medication sooner. Injection naltrexone is given at a dose of 380 mg once a month, but it can be given once every three weeks (Strain, 2019).

Side effects of naltrexone include headache, nausea, dizziness, and fatigue. In rare situations, liver damage may occur but is usually seen with high doses and typically resolves when the medication is stopped. However, patients who stop antagonist therapy and restart opioids are at high risk for overdose secondary to loss of tolerance (Strain, 2019).

Table 6: Naloxone Challange Test
A naloxone challenge test can be done to assure the patient is wholly withdrawn from opioids. Before starting the test, the patient should not have any apparent signs of opioid withdrawal. Before administering naloxone, a set of vital signs is taken. The patient is watched for one hour and monitored for any signs/symptoms of withdrawal, using a standardized scale; if the patient demonstrates any withdrawal or increase in pulse or blood pressure, the patient fails the challenge.

Case Study 1

A 22-year old male is seen in the clinic accompanied by his mother. His mother reports that he has been unable to eat and has had diarrhea for the last 24 hours. He recently moved home to live with his mother after dropping out of college. He reports that he was using prescription opiates for the last six months after a knee injury and then moved on to heroin use. The patient reports he is restless, nauseous, has diarrhea, has a runny nose, yawning, and sweating. He is noted to have a blood pressure of 146/88 mm Hg on physical exam, a heart rate of 116, he is noticeably restless, has beads of sweat on his forehead, and has a noticeable tremor. The Clinical Opioid Withdrawal Scale (COWS) score is 19, which puts him in moderate withdrawal.

The APRN who evaluates the patient has a DATA 2000 waiver and a Drug Enforcement Administration (DEA) certification to prescribe buprenorphine to treat opioid use disorder. As part of the examination, the ARNP takes a history of presenting illness, a medical and psychiatric history, a drug use history, a social and family history. In addition, the APRN performs a focused physical exam.

Labs were drawn, demonstrating a normal complete blood count, negative HIV screen, normal kidney function, and electrolytes; alanine aminotransferase (ALT) increased two times above the normal limit. The comprehensive drug screen was positive for opioids. The APRN contacted the prescription drug monitoring program, reviewed prescriptions for the last 12 months, and confirmed a prescription for hydrocodone with acetaminophen and a lorazepam prescription.

The patient signed a release of information to get a copy of his medical records from the provider prescribing opiates for his knee and the emergency room evaluations he had over the last year.

The APRN discussed treatment options with the patients and obtained informed consent to use buprenorphine for acute withdrawal. In addition, the APRN prescribed bismuth for diarrhea and ondansetron for nausea.

After documenting the presence of the opioid withdrawal symptoms and the COWS score of 19, the patient was given buccal buprenorphine 2.1 mg/naloxone 0.3 mg for in-office observed induction. After two hours, the patient was better, but the COWS score was 12, so a repeat dose was given. After one hour, the patient has a COWS score of 6 and is only slightly sedated. He is sent home and returns to the clinic the next day. At that point, he has a COWS score of 16 and is given buprenorphine 4.2 mg/naloxone 0.7 mg as a one-time dose. He is observed for two hours in the clinic and is noted to have a COWS score of five after those two hours.

A follow-up appointment is set for one week, and he is given a one-week prescription of buprenorphine/naloxone. He is then scheduled every week for the next month and then every two weeks for the following months. The patient does well, has not gone back to opioid use, and has no ill effects of buprenorphine/naloxone. He is scheduled for monthly evaluations for the next two years. For the first year, he has a drug screen at each of the visits.

As part of the initial plan, the patient must see a mental counselor with expertise in addiction and join a 12-step program.

Treatment of Alcohol Use Disorder

Some research puts the prevalence of alcohol use disorder between 20-36 percent (Saxon & Strain, 2019). While psychosocial interventions to treat alcohol use disorder can be effective, up to 70 percent of people return to heavy drinking after psychosocial treatment alone (Saxon & Strain, 2019). Adding medication to the management of alcohol use disorder may increase the days of abstinence and reduce heavy drinking (Saxon & Strain, 2019).

The first step in the management of alcohol use disorder is to evaluate for withdrawal. Alcohol withdrawal presents irritability, depression, anxiety, mood swings, shakiness, fatigue, sweating, anorexia, tremor, headache, dilated pupils, nausea/vomiting, and an elevated heart rate. If symptoms of withdrawal are not managed, then most patients will not progress with treatment.

Medications for alcohol use disorder (AUD) are effective for those with moderate to severe AUD. However, the effectiveness of medication on mild disease is not conclusive (Saxon & Strain, 2019).

Patients with moderate to severe AUD should combine psychosocial intervention, self-help groups, medications, and social services if needed. Research suggests that naltrexone alone may be somewhat effective (Saxon & Strain, 2019).

For mild disease, psychosocial interventions are recommended as first-line treatment (Saxon & Strain, 2019). Counseling or participation in mutual-help groups is an effective option as a psychosocial intervention. The content of the programs is variable, and there is limited research that answers which is the most effective psychosocial intervention. Specific programs include behavioral intervention, which includes 12 step programing, motivational interviewing, and cognitive-behavioral therapy. Individuals who have family or partner problems could use couple or family therapy. Individuals who have low motivation to change benefit from counseling to address the low motivation and help move them toward treatment as AUD affects the part of the brain responsible for decision making.

Medications in Alcohol Use Disorder

The first-line treatment in AUD is naltrexone, but acamprosate may be used. Both medications have evidence to show effectiveness (Saxon & Strain, 2019). In addition, research suggests that both agents have similar effectiveness in reducing rates of return to heavy drinking (Saxon & Strain, 2019).

Naltrexone

For alcohol use disorder, oral naltrexone is usually started at is 50 mg/day but can be increased to 100 mg/day. For patients with poor adherence to daily treatment, the use of long-acting naltrexone can be considered. The long-acting form is dosed at 380 mg intramuscularly monthly. Naltrexone can be started when the patient is drinking.

Naltrexone must be used cautiously. It is associated with hepatotoxicity – especially with high doses. Naltrexone cannot be used in those on an opioid but can be used effectively for those with both OUD and AUD.

Acamprosate

Before starting acamprosate, the patient should be abstinent. American trials for acamprosate have not been effective, and most positive research was done in Europe. When liver enzymes are increased, the use of acamprosate is recommended over naltrexone. Adjustments need to be made for renal impairment. When the creatinine clearance is less than 30 mL/min, then the medication is contraindicated. The dose should be halved in those with a creatine clearance between 30 and 50 mL/min. The use of acamprosate is recommended over naltrexone in those currently taking an opioid, although using an opioid in someone with an alcohol use disorder is not recommended (Saxon & Strain, 2019).

There is limited data on the safety of these medications in pregnant women. However, pregnant patients with heavy alcohol use are at high risk of damage to the fetus, and medication should be considered in those who continue drinking. Naltrexone is the more commonly used medication in pregnancy. Only those with expertise should treat AUD in pregnancy.

Abstinence is the optimal treatment goal as it is often difficult for patients to maintain alcohol consumption at a safe level. Those who remain abstinent have a better outcome, but any reduction in alcohol use will provide benefit.

Disulfiram is another medication that helps with AUD. When taken, it is associated with adverse effects when mixed with alcohol. It is meant to help individuals maintain abstinence. The dose for disulfiram is 125 to 500 mg a day, and it works best when taking the medication is supervised.

Naltrexone can be started without the need to detox the patient. Drinking should not occur when patients are on acamprosate or disulfiram. When acamprosate is started, it will inhibit the desire to go back to drinking. Disulfiram will lead to adverse effects when alcohol is consumed.

After treatment is started, at least weekly follow-up should occur. During these visits, the patient should be assessed, supported, and family members engaged (if indicated). In addition, patients should be monitored for treatment effectiveness, adherence, side effects, and any relapse signs.

Toxicology testing can be done and is most helpful in early treatment (Saxon & Strain, 2019). Testing is often done by urine screening and typically detects if any alcohol has been ingested in the last 72 hours, but it does not quantify how much alcohol was consumed. In addition, urine ethyl glucuronide testing can give a false positive test in those exposed to hand sanitizers.

Blood work can also be used to test for alcohol use. For those who have elevated reading of gamma-glutamyl transferase (GGT) and carbohydrate-deficient transferrin at baseline, these two tests can be used to determine if the patient has engaged in heavy drinking. GGT is nonspecific but less expensive and more widely available. Carbohydrate-deficit transferrin is specific but more expensive. Neither test is sensitive and may miss some people who have been drinking (Saxon & Strain, 2019).

Patients who have an adequate response to treatment should continue with psychosocial treatment for six to twelve months. Medication treatment should be continued for at least one year. More prolonged treatment is associated with a lower risk of recurrence, but the exact length of time to maintain treatment is unknown. Treatment with naltrexone, acamprosate, and disulfiram can be stopped abruptly, and no tapper is needed. Continued monitoring should occur after treatment when medication is discontinued.

It is challenging to determine the exact length of time required to assess if a treatment has been effective. Psychosocial treatments may take weeks to have effects. Medications tend to work faster. Those on disulfiram will quickly be able to tell if there is a success with the treatment. With naltrexone and acamprosate, it may take weeks to assess if benefits are noticed. Reductions in the frequency of heavy drinking may occur over months; this is especially relevant when drinking is not daily (Saxon & Strain, 2019).

Certain factors require a greater urgency to getting control of AUD. Those at high risk for suicide or pregnant women need to be assessed to assure treatment is effective quickly.

Individuals who do not have an adequate initial response may benefit from increasing the frequency or intensity of interventions—for example, going to more groups per week, moving from outpatient treatment to day treatment, or adding medication. Medications can also be modified. If continued drinking occurs, increasing the dose may reduce cravings. Research has shown that higher doses of naltrexone reduce alcohol cravings (Brünen et al., 2019).

Generally, naltrexone and acamprosate are first-line agents for alcohol use disorder as they have the most evidence for effectiveness. If naltrexone was used and was not effective, switching to acamprosate should be considered. If acamprosate was used first and it was not effective, switching to naltrexone should be considered. When the patient does not respond to either naltrexone and acamprosate, other options include disulfiram and topiramate.

Topiramate is sometimes used for the management of AUD. It is dosed up to 300 mg a day. Topiramate, while effective, is associated with multiple side effects that some patients cannot tolerate. The patient may experience fatigue, dizziness, cognitive impairment, depression, weight loss, or paresthesia. Topiramate is the only AUD medication that requires a taper when stopped.

Combination medications are sometimes used in the management of AUD. When one agent does not work, adding another medication with a different mechanism of action may be beneficial. For example, the use of naltrexone and acamprosate has been found to work better than individual medications (Saxon & Strain, 2019).

Treatment of Cannabis Use Disorder

Treatment goals of cannabis use disorder (CUD) may be abstinence or reduction in use until problems do not occur secondary to cannabis use. Reduction in use is a more common goal in those with mild CUD. Motivational interviewing is a critical aspect of the early treatment of CUD. The patient needs to identify the benefits and harms of cannabis use.

For individuals with heavy use, there may be a withdrawal syndrome. Withdrawal is characterized by anxiety, irritability, sleep disturbance, depression, and anger. Symptoms typically occur 1-3 days after stopping use and peak within the first week, with the resolution being noted within two weeks (Gorelick, 2021). Withdrawal from synthetic cannabis may be associated with tachycardia, hypertension, seizures, mental status change, and diaphoresis.

It is important to make patients aware of the withdrawal syndrome. Treatment of symptoms associated with the withdrawal can be beneficial in making the patient more comfortable and reducing the risk of relapse. Those with mild withdrawal can be treated with exercise, relaxation, medication, and improved sleep.

Patients with more significant withdrawal are at greater risk for relapse, and these patients are more likely to benefit from treatment of the withdrawal. Zolpidem effectively manages sleep issues in those with insomnia related to cannabis withdrawal (Gorelick, 2021). Dronabinol and gabapentin are sometimes used in those with cannabis withdrawal.

Psychosocial interventions are recommended as first-line treatment for CUD. No medications have shown consistent efficacy for CUD. Treatment for CUD should include CBT or motivational enhancement treatment. Both interventions have shown similar benefits, but CBT is slightly more effective (Gorelick, 2020). CBT for CUD works to identify and manage thoughts, behaviors, and external triggers that promote use. Then the patient is taught healthier alternatives to cannabis use along with problem-solving and coping skills. Motivational interviewing includes working with patients to modify their negative behaviors and enhance motivation to maintain treatment and sustain abstinence.

If one intervention does not work alone, combining the treatments should be considered using mutual help groups, such as marijuana anonymous. If psychosocial interventions are ineffective, medications may be tried, but no medication has shown significant efficacy (Gorelick, 2020).

A meta-analysis has shown that those receiving psychosocial interventions were twice as likely to abstain or reduce cannabis use at 3-4 months as those with no intervention (Patnode et al., 2020).

For those with cannabis use disorder, a brief intervention that usually consists of one or two fifteen to twenty minutes counseling sessions with motivational techniques has been shown in some studies to reduce cannabis use (Gorelick, 2021).

No medications are approved for CUD, but a few medications have shown a slight benefit in small trials, and some clinicians use them when psychosocial interventions fail. Medications that have shown some benefits include N-acetylcysteine, gabapentin, and cannabidiol. Many other drugs have been purported to benefit CUD, but they have not demonstrated any clinical benefit, including antidepressants, buspirone, lithium, topiramate, and divalproex (Gorelick, 2020).

Case Study 2

A 32-year-old inmate is being released from prison after a 12 months sentence for possession of illegal substances. He is generally healthy, but he was diagnosed with alcohol use disorder, opioid use disorder, and hepatitis C while incarcerated.

Before release, he worked with recovery services in the prison system, going through programming, receiving individual counseling, and participating in mutual-help groups (Alcoholic Anonymous and Narcotics Anonymous). When visiting with his drug counselor, he lets her know that he would like some medication to help him with his alcohol and drug use after release from prison.

He is referred to the APRN for evaluation to determine what/if any medication can help him. After a conversation with the patient, it was determined that naltrexone would be the best option as it is effective for both opioid and alcohol use disorder. He is concerned regarding his ability to take a daily medication, so it was determined that the monthly naltrexone injection would be the best option.

Naltrexone is often used in correctional settings for opioid use disorder as it is an opioid antagonist and does not have analgesic activity and essentially no abuse potential. In addition, it is best used in patients who are detoxified from opiates, and as this patient has been in prison for the last year, so likely, he has not been using illicit drugs.

The APRN is concerned that the naltrexone may further damage his liver, given his hepatitis C and history of alcohol use and injection drug use. Naltrexone is associated with low rates of liver enzyme elevation, and rarely does it lead to liver injury, and only one percent of patients have a liver enzyme rise more significant than three times the upper limit of normal (NIH, 2018)

The liver quickly metabolizes naltrexone to its inactive form, and the etiology of hepatic injury is unknown but may be dose-dependent direct toxicity. If liver enzymes are significantly increased, discontinuing therapy typically reverses the levels, but many cases reverse even if therapy is continued. While naltrexone is potentially a hepatoxic agent, it has not been definitively linked to hepatotoxicity (NIH, 2018).

Table 7: Labs for Case Study 2
TestValueNormal
alanine aminotransferase (ALT)54 IU/L0-44 IU/L
aspartate aminotransferase (AST)36 IU/L0-40 IU/L
Urine Drug ScreenNegativeNegative

After a follow-up evaluation from the APRN, where the liver enzymes are reviewed and deemed appropriate for therapy, he is given the naltrexone injection. He is scheduled to be released from prison two weeks later.

He comes back to the medical department two days after the injection with insomnia, dizziness, headache, nausea, and mild diarrhea. He is thoroughly evaluated, and the exam is benign. It is explained to him that these are common side effects of naltrexone.

The recovery service team set up an appointment for the patient with an addiction treatment center in the community after release to assist with psychosocial services to help keep him off opioids, alcohol, and other drugs. In addition, he is set up for an appointment in 2 more weeks for another naltrexone injection.

Conclusion

Addiction is a debilitating disease that is associated with significant brain pathology. Addiction can result from many substances including, alcohol, opiates, and cannabis. It can lead to significant morbidity and even mortality. Clinicians need to be well versed in the evaluation, diagnosis, and treatment of multiple types of addiction.

Opioid addiction has become a significant problem in recent years. Fortunately, the literature has become much more robust regarding the evaluation and treatment of addiction to opioids. Many good treatment options are now available in the treatment of opioid use disorder, including buprenorphine. While buprenorphine is very effective in the management of opioid use disorder, it is associated with risks.

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Reference

  • ACOG. (2019). Opioid Use and Opioid Use Disorder in Pregnancy - ACOG. ACOG Committee Recommendations, 130(711), 81–94. Visit Source.
  • American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Visit Source.
  • ASAM. (2020). ASAM Definition of Addiction. Visit Source.
  • Black, E., Khor, K. E., & Demirkol, A. (2020). Responsible Prescribing of Opioids for Chronic Non-Cancer Pain: A Scoping Review. Pharmacy, 8(3), 150. Visit Source.
  • Bradley, K. A., Debenedetti, A. F., Volk, R. J., Williams, E. C., Frank, D., & Kivlahan, D. R. (2007). AUDIT-C as a brief screen for alcohol misuse in primary care. Alcoholism: Clinical and Experimental Research, 31(7), 1208–1217. Visit Source.
  • Brünen, S., Bekier, N. K., Hiemke, C., Korf, F., Wiedemann, K., Jahn, H., & Kiefer, F. (2019). Therapeutic drug monitoring of naltrexone and 6β-naltrexol during anti-craving treatment in alcohol dependence: Reference ranges. In Alcohol and Alcoholism (Vol. 54, Issue 1, pp. 51–55). Oxford University Press. Visit Source.
  • CDC. (2017). Fast Facts and Fact Sheets | Marijuana | CDC. Visit Source.
  • Centers for Disease Control and Prevention; National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention. (2020). Heroin Overdose Data | Drug Overdose | CDC Injury Center. Opioid Overdose. Visit Source.
  • Comer, S., Cunningham, C., Fishman, M. J., Gordon, A., Kampman, K., Langleben, D., Nordstrom, B., Oslin, D., Woody, G., Wright, T., Wyatt, S., Femino, J., Jarvis, M., Kotz, M., Pirard, S., Roose, R. J., Geier-Horan, A., Staff, A., Haynes, B., … Woodworth, A. (2015). National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use Guideline Committee Members (alpha or. Visit Source.)
  • Degenhardt, L., Bruno, R., Lintzeris, N., Hall, W., Nielsen, S., Larance, B., Cohen, M., & Campbell, G. (2015). Agreement between definitions of pharmaceutical opioid use disorders and dependence in people taking opioids for chronic non-cancer pain (POINT): A cohort study. The Lancet Psychiatry, 2(4), 314–322. Visit Source.
  • Dowell, D., Haegerich, T. M., & Chou, R. (2016). CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016 Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention: MMWR Recommendations and Reports, 65(1). Visit Source.
  • Dugosh, K. L., Cacciolo, J. S. (2019). Clinical assessment of substance use disorders - UpToDate. UpToDate®. Visit Source.
  • FDA. (2020). Information about Naloxone | FDA. FDA. Visit Source.
  • Gorelick, D. A. (2020). Cannabis use in Adults. UpToDate®. Visit Source.
  • Gorelick, D. A. (2021). Cannabis withdrawal. Visit Source.
  • Gowing, L., Farrell, M., Ali, R., & White, J. M. (2016). Alpha2-adrenergic agonists for the management of opioid withdrawal. In Cochrane Database of Systematic Reviews (Vol. 2016, Issue 5). John Wiley and Sons Ltd. Visit Source.
  • Gowing, L., Ali, R., White, J. M., & Mbewe, D. (2017). Buprenorphine for managing opioid withdrawal. The Cochrane Database of Systematic Reviews, 2(2), CD002025. Visit Source.
  • Haight, B. R., Learned, S. M., Laffont, C. M., Fudala, P. J., Zhao, Y., Garofalo, A. S., Greenwald, M. K., Nadipelli, V. R., Ling, W., Heidbreder, C., Andersen, J. L., Bailey, G. L., Bartley, S. R., Biunno, M. J., Boyett, B., Carr, J. M., Cifuentes, E., Duarte-Sckell, S. D., Dueno, O. R., … Wiest, K. L. (2019). Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 393(10173), 778–790. Visit Source.
  • Han, B., Volkow, N. D., Compton, W. M., & McCance-Katz, E. F. (2020). Reported Heroin Use, Use Disorder, and Injection among Adults in the United States, 2002-2018. In JAMA - Journal of the American Medical Association (Vol. 323, Issue 6, pp. 568–571). American Medical Association. Visit Source.
  • Hedegaard, M.H., Warner, M, and Miniño, A. M. . (2017). Products - Data Briefs - Number 294 - December 2017. Visit Source.
  • Hoots, B. E., Xu, L., Kariisa, M., Wilson, N. O., Rudd, R. A., Scholl, L., Schieber, L., & Seth, P. (2018). 2018 ANNUAL SURVEILLANCE REPORT OF DRUG-RELATED RISKS AND OUTCOMES UNITED STATES. Visit Source.
  • Kentucky Administrative Regulations. (2021). 201 BOARDS AND COMMISSIONS Chapter: \201\020.065. Visit Source.
  • Lee, J. D., Nunes, E. V., Novo, P., Bachrach, K., Bailey, G. L., Bhatt, S., Farkas, S., Fishman, M., Gauthier, P., Hodgkins, C. C., King, J., Lindblad, R., Liu, D., Matthews, A. G., May, J., Peavy, K. M., Ross, S., Salazar, D., Schkolnik, P., … Rotrosen, J. (2018). Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X: BOT): a multicentre, open-label, randomised controlled trial. The Lancet, 391(10118), 309–318. Visit Source.
  • Ling, W., Nadipelli, V. R., Aldridge, A. P., Ronquest, N. A., Solem, C. T., Chilcoat, H., Albright, V., Johnson, C., Learned, S. M., Mehra, V., & Heidbreder, C. (2020). Recovery From Opioid Use Disorder (OUD) After Monthly Long-acting Buprenorphine Treatment: 12-Month Longitudinal Outcomes From RECOVER, an Observational Study. Journal of Addiction Medicine, 14(5), e233–e240. Visit Source.
  • Manchikanti, L., Abdi, S., Atluri, S., Balog, C. C., Benyamin, R. M., Boswell, M. V., Brown, K. R., Bruel, B. M., Bryce, D. A., Burks, P. A., Burton, A. W., Calodney, A. K., Caraway, D. L., Cash, K. A., Christo, P. J., Damron, K. S., Datta, S., Deer, T. R., Diwan, S., … American Society of Interventional Pain Physicians. (2012). American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician, 15(3 Suppl). Visit Source.
  • McKay, J. R. (2020). Continuing care for addiction: Context, components, and efficacy - UpToDate. UpToDate®. Visit Source.
  • McKay, James R. (2020). Psychotherapies for substance use disorders - UpToDate. UpToDate. Visit Source.
  • National Institute on Drug Abuse. (2017). Costs of Substance Abuse | NIDA Archives. Visit Source.
  • Nida. (n.d.). Clinical Opiate Withdrawal Scale. Retrieved May 26, 2021, from Visit Source.
  • NIDA. (2020a). Anxiety and Stress Found to Promote Cocaine Use in Rats | NIDA Archives. Visit Source.
  • NIDA. (2020b). Criminal Justice DrugFacts | National Institute on Drug Abuse. Visit Source.
  • NIH. (2018). Non-Drug Pain Management: MedlinePlus. Medline. Visit Source.
  • Patnode, C. D., Perdue, L. A., Rushkin, M., Dana, T., Blazina, I., Bougatsos, C., Grusing, S., O’Connor, E. A., Fu, R., & Chou, R. (2020). Screening for Unhealthy Drug Use: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. In JAMA - Journal of the American Medical Association (Vol. 323, Issue 22, pp. 2310–2328). American Medical Association. Visit Source.
  • Pearce, L. A., Min, J. E., Piske, M., Zhou, H., Homayra, F., Slaunwhite, A., Irvine, M., McGowan, G., & Nosyk, B. (2020). Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: Population based retrospective cohort study. The BMJ, 368. Visit Source.
  • Peavy, K. M. (2021). Psychosocial interventions for opioid use disorder. Visit Source.
  • Pergolizzi, J. V., Annabi, H., Gharibo, C., & LeQuang, J. A. (2019). The Role of Lofexidine in Management of Opioid Withdrawal. Pain and Therapy, 8(1), 67–78. Visit Source.
  • Rodriguez, C. E., & Klie, K. A. (2019). Pharmacological treatment of opioid use disorder in pregnancy. In Seminars in Perinatology (Vol. 43, Issue 3, pp. 141–148). W.B. Saunders. Visit Source.
  • Saitz, R. (2017). Screening for unhealthy use of alcohol and other drugs in primary care. In UpToDate (pp. 1–19). Visit Source.
  • Saitz, R. (2020). Screening for unhealthy use of alcohol and other drugs in primary care. Visit Source.
  • SAMHSA. (2019). 2019 National Survey of Drug Use and Health (NSDUH) Releases | CBHSQ Data. Visit Source.
  • Saxon, A. J., & Strain, E. (2019). Approach to treating alcohol use disorder. UpToDate, 1–25. Visit Source.
  • Sevarino, K. (2020). Medically supervised opioid withdrawal during treatment for addiction. UpToDate. Visit Source.
  • Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ (Clinical Research Ed.), 357, j1550. Visit Source.
  • Strain. E. (2019). Pharmacotherapy for opioid use disorder - UpToDate. UptoDate. Visit Source.
  • Strain, E. (2021). Pharmacotherapy for opioid use disorder. Visit Source.
  • Strain, E., Saxon, A. J., & Solomon, D. (2020). Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis - UpToDate. 1–20. Visit Source.
  • Substance Abuse and Mental Health Services Administration (SAMHSA). (2021). Home Page | CBHSQ Data. Visit Source.
  • Substance Abuse and Mental Health Services Administration (SAMHSA), Bose, J., Hedden, S. L., Lipari, R. N., Park-Lee, E., Tice, P., & Substance Abuse and Mental Health Services Administration. (2018). Key Substance Use and Mental Health Indicators in the United States: Results from the 2017 National Survey on Drug Use and Health Recommended Citation Substance Abuse and Mental Health Services Administration (HHS Publication No. SMA 18-5068, NSDUH Series. In HHS Publication No. SMA 18-5068, NSDUH Series H-53. Visit Source.
  • Tanum, L., Solli, K. K., Latif, Z. E. H., Benth, J. Š., Opheim, A., Sharma-Haase, K., Krajci, P., & Kunøe, N. (2017). Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: A randomized clinical noninferiority trial. JAMA Psychiatry, 74(12), 1197–1205. Visit Source.
  • The Substance Abuse and Mental Health Services Administration. (2019). Chapter 3B: Methadone - Medications for Opioid Use Disorder - NCBI Bookshelf. Visit Source.
  • Tice, P. (2016). Results from the 2015 national survey on drug use and health. Center for Behavioral Health Statistics and Quality, 3263. Visit Source.
  • Wesson, D. R., & Ling, W. (2003). The clinical opiate withdrawal scale (COWS). Journal of Psychoactive Drugs, 35(2), 253–259. Visit Source.
  • Wilson, N., Kariisa, M., Seth, P., Smith, H., & Davis, N. L. (2020). Drug and Opioid-Involved Overdose Deaths — United States, 2017–2018. MMWR. Morbidity and Mortality Weekly Report, 69(11), 290–297. Visit Source.
  • World Health Organization. (2021). Palliative care. Nippon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics. Visit Source.
  • Zedler, B. K., Mann, A. L., Kim, M. M., Amick, H. R., Joyce, A. R., Murrelle, E. L., & Jones, H. E. (2016). Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus, and child. In Addiction (Vol. 111, Issue 12, pp. 2115–2128). Blackwell Publishing Ltd. Visit Source.