Medication Assisted Treatment (MAT)

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Introduction   

Medication Assisted Treatment (MAT) is a treatment modality for substance use disorders. It combines counseling and behavioral therapies for addiction with medications used carefully to reduce the physical symptoms of cravings and withdrawal and assist clients in the recovery process. With half of people 12 and older reporting use of an illicit substance at least once and 21 million Americans experiencing addiction, this is an important and relevant topic (4).

Historically, an intense stigma is attached to both addiction and some of the medications used to treat addiction. A thorough understanding of substance use disorders, available MAT therapies, and care of affecting clients are essential topics for nurses to be familiar with, particularly those working in psychiatry, pain management, or addiction medicine.

Overview of Addiction and Substance Abuse:

Drug and alcohol abuse and addiction are chronic, complicated issues involving persistent changes to the brain. There is a stigma or misunderstanding that people with substance abuse disorders can stop any time they want to or lack the willpower or moral fortitude to stop using. This is entirely untrue, and even people who are "recovering" and have not had any drugs or alcohol in years can easily relapse into addiction once those brain changes have occurred (5).

When a person uses drugs or alcohol, the brain's reward center is flooded with dopamine. This provides a "buzz" or pleasurable sensation that may create the desire to use more of the same substance. Over time, and with regular use of the substance, the brain becomes accustomed to the flooding of dopamine and reduces the reward response, a process known as tolerance.

It will now take the same person a more significant amount of the substance to achieve the same "buzz" or "high" they used to feel. This process can also dull the pleasure response to activities not involving substance use, such as food, socialization, or sexual activity. Over time, the chemical changes in the brain can progress to include decreased functioning of learning, decision-making, judgment, response to stress, memory, and behavior (5).

To understand substance abuse disorders, it is first essential to understand some basic definitions. These terms are sometimes used interchangeably, but they mean different things and represent different stages of disease.

Definitions

Substance Use: Substance use is any consumption of drugs or alcohol, regardless of frequency or amount. An occasional glass of wine or taking an edible at a party is an example of substance use. Substance use does not cause problems or dependency in many people (5).

Substance Abuse: Substance abuse is the continued use of drugs or alcohol, even when they do cause problems. Conflict or problems at home, school, work, or legal issues related to the use of drugs or alcohol are signs of abuse. For example, being sent home from school for smoking in the bathroom or failing a drug test at work (5).

Substance Dependence or Addiction: Dependence and addiction can be used interchangeably or is sometimes called substance use disorder. Addiction occurs when a person cannot stop drinking or using drugs despite creating problems in their life. People who are addicted may experience cravings until they use a specific substance, or they may experience uncomfortable physical symptoms, known as withdrawal if they do stop (5).

The American Psychiatric Association (APA) utilizes the following criteria to diagnose clients who suffer from addiction. The more criteria a client answers yes to, the greater their problem with substance use.

Six or more positive criteria are indicative of addiction.

1. Using substance in more significant amounts or for more extended periods than intended
2. Trying to stop using but being unable to
3. Increased amounts of time getting, using, or recovering from use of the substance
4. Experiencing cravings or urges to use.
5. Continuing to use the substance despite problems with relationships or social situations.
6. Missing work, social, or recreational obligations or activities because of substance use
7. Participating in risky behavior because of substance use
8. Continuing to use the substance despite psychological or physical health problems.
9. Needing to use more substance over time to achieve the desired effect.
10. Experiencing withdrawal symptoms when stopping the substance (1).

Substance Abuse Statistics

Many factors go into gathering data on substance abuse disorders, from underreporting, the nuance between use, abuse, and addiction, and the large variety of substances available, with the legality of some substances varying by state or age.

The statistics below from 2020 are not meant to be an exhaustive list of substance use disorders in this country but rather an overview of some of the more prevalent addiction-related issues.

• 50% of people 12 years and older have used an illicit substance at least once.
• 5% of Americans 12 years and older have used drugs within the last month.
• This is a 3.8% increase from the previous year.
• About 50% of Americans 12 and over drink alcohol
• 4% of those people have an alcohol use disorder.
• About 20% of Americans use tobacco products or vape
• 18% of Americans over 18 used marijuana in the last 12 months
• 30% of those have some level of misuse or addiction.
• Marijuana is commonly involved in polysubstance use, paired with alcohol or other drugs.
• 7% of Americans over 12 misused opioids in the last 12 months
• 96% of those used prescription pain relievers
• Opioid prescriptions peaked in 2012, with 81.3 prescriptions per 100 people.
• The rate has declined recently due to increased attention to this crisis.
• In 2018, the rate was down to 51 prescriptions for every 100 people
• Fentanyl is now rising as a new and deadly concern.
• 5 million prescriptions were written for fentanyl in 2015.
• Fentanyl is involved in 53% of overdose deaths.
• 7% of all Americans misuse a prescription drug.
• 1% of those misuse stimulants
• 2% of those misuse sedatives
• 5% misuse painkillers
• Over 70,000 drug overdose deaths occur annually in the United States (4)

Risk Factors

A combination of factors is involved in the risk of addiction, and no one factor can determine if someone will develop addiction or after how many uses this will occur.

The addiction process does occur more easily or progresses more rapidly for people with certain risk factors, including:

Genetics

There is a strong genetic correlation with addiction, indicating that biology plays a significant role in the disorder. Family history of addiction, gender, ethnicity, and comorbid mental health conditions can all influence the risk of addiction. (5)

• Children of addicts are eight times more likely to develop an addiction at some point.
• In 2020, among those using illicit or misusing prescription drugs, 22% were male and 17% female.
• Only 20% of users in drug treatment programs are women.
• 9% of people with substance abuse disorders also have at least one mental health disorder (4)

Environment/Non-Genetic Demographics

The attitudes about drugs and alcohol from those in a person's network and life experiences play a role in the risk of addiction. Substance use among friends, family, or coworkers increases the risk that a person will also use substances. Exposure to substance use from a young age relaxed parental attitudes about substance use, and peer pressure from friends can increase the risk. Certain stressful life circumstances such as veteran status, history of sexual or physical assault, or being part of the LGBTQ community can also increase risk. (5)

• 20% of people in urban areas used illegal drugs in 2020 compared to 5% in rural locations.
• 51% of Americans with an illegal pain relief medication obtained it from a friend or relative.
• 7% of LGBTQ Americans abuse illicit drugs.
• 2% of LGBTQ Americans abuse alcohol.
• 7% of Veterans abuse illicit drugs.
• 80% of Veterans abuse alcohol (4)

Developmental Stage

Substance use at any age can lead to addiction, but children and teens are at particular risk due to their underdeveloped brains. The parts of the brain responsible for decision-making, risk assessment, and self-control do not fully develop until the early 20's, putting teenagers at increased risk of dangerous behaviors. In addition, the effects of drugs and alcohol on the developing brain may mean that those parts of the brain never fully develop at all for teens with substance abuse disorders. (5)

• 70% of users who try an illegal substance before age 13 will develop a substance use disorder within the next seven years.
• This is for only 27% of people who first try an illegal substance after age 17.
• 47% of youths report trying an illegal substance by the time they graduate high school (4)

Overview of Medication Assisted Treatment (MAT)

Treatment of substance abuse disorders is a complex and often tumultuous process. The nature of the brain changes that occur during addiction means that a person is never entirely "cured" but will always be considered "recovering" as the risk for relapse is always present. Effective treatment must be multifaceted and often involves removing triggers (such as people, places, and stressors) that may prompt a person to use again behavioral therapy, and medications to curb withdrawal symptoms and reduce cravings.

Medication Assisted Treatment (MAT) is a treatment that involves FDA-approved medications, in combination with behavioral therapy, in the recovery process for substance abuse disorders. Several medications are available for MAT, and evidence continues to emerge that the treatment is highly effective if used correctly.

However, it is a vastly underused and understudied treatment modality. MAT has been available in some form for over 50 years but is just starting to gain traction among the medical community (and policymakers) in recent years, with the federal government calling for more research and increased accessibility for the treatment (8).

The height of the opioid crisis in the last several years has highlighted the magnitude of drug addiction and deaths in the United States, bringing renewed attention to MAT as a treatment option. So, how does MAT work? Prescription medication is given to both stimulate the receptors seeking the abused substance and block the drug's euphoric effects.

Over time, this normalizes brain chemistry and helps the person break the habit of using without the discomfort of cravings and withdrawal symptoms. Gradually, the prescription medication dosage is reduced, all the while in conjunction with behavioral therapy and lifestyle changes, and eventually, the client should be able to stop the medication altogether, often within 1-3 months (8).

MAT does require close supervision by a trained medical professional and an appropriate facility for treatment. It can be done on an inpatient, partial inpatient, or outpatient basis. There may be side effects to the medication, and there is a risk of misusing or developing addiction to the new drug, though the successful outcomes often outweigh this risk. Clients must also participate in behavioral therapy for a comprehensive and effective treatment plan. As with any treatment regimen, careful consideration of the client's history and circumstances is essential (8).

Pharmacokinetics

Currently, there are three medications with FDA approval for MAT: buprenorphine, methadone, and naltrexone. Each will be discussed in depth below.

Buprenorphine

Mechanism of Action and Metabolism

Buprenorphine is an opioid partial agonist, acting on the same receptors as other opioids but with weaker effects. It can be used for the treatment of misuse of opioids, including:

• Heroin
• Fentanyl
• Oxycodone
• Hydrocodone
• Morphine
• Methadone (3)

Opiate receptors are G-protein coupled receptors (GPCRs) with four major types: Mu, Delta, Kappa, and opioid receptor like-1 (ORL1). Stimulation of these receptors results in varying levels of the following effects:

• Euphoria
• Relaxation
• Pain relief
• Sleepiness
• Sweating
• Constipation
• Impaired concentration
• Reduced sex drive (3)

Buprenorphine has a high affinity to the Mu-opioid receptor and is a partial agonist at this site, causing reduced opioid effects with a plateau or ceiling at higher doses. This limits dangerous effects and makes overdose unlikely. It also has slow dissociation from the site, allowing milder and more easily tolerated withdrawal effects compared to full agonists like morphine and fentanyl. Buprenorphine is also a weak kappa receptor antagonist and delta receptor agonist, reducing the craving sensation and improving tolerance to stress (3).

Buprenorphine has poor bioavailability when given orally due to the first-pass effect, where most of the drug is broken down in the liver and intestines. Because of this, sublingual or buccal are the preferred routes of administration and the most common forms in which the drug is manufactured. Transdermal patches and IV and IM forms exist, though not for use in MAT (3).

CYP34A enzymes break down buprenorphine, so other drugs, such as ketoconazole, may inhibit metabolism and increase available levels of buprenorphine. CYP34A inducers such as carbamazepine, topiramate, phenytoin, and barbiturates may speed metabolism and lower available levels. Once broken down, the med takes the form of norbuprenorphine and is excreted in the feces (3).

Available Forms

Buprenorphine is available by itself and with naloxone (in a 4 to 1 ratio). However, in oral form, naloxone is not readily absorbed, and buprenorphine is the only genuinely active ingredient. This combination is beneficial should clients try to inject their buprenorphine to get high; naloxone is a fast-acting opioid antagonist that is active when used intravenously and would block the opioid effect of buprenorphine, rendering it useless for recreational use and ensuring it has no street value.

The currently available preparations of buprenorphine for MAT include:

• Generic Buprenorphine/naloxone sublingual tablets
• Subutex - Buprenorphine sublingual tablets
• Suboxone - Buprenorphine/naloxone sublingual films
• Zubsolv - Buprenorphine/naloxone sublingual tablets
• Bunavail - Buprenorphine/naloxone buccal film (3)

Sublingual products dissolve within 2-10 minutes. Bloodstream absorption begins quickly, bypassing the first pass effect. Buprenorphine has a slow onset of action, peaking about 3-4 hours later. Metabolism is also slow, with the half-life lasting anywhere from 25 to 70 hours (an average of about 38 hours). This long half-life means the drug can be spaced out to every other day administration once weaning begins (3).

Dosing and Monitoring

Clients prescribed buprenorphine must stop using opioids for at least 12 to 24 hours before the first dose; this varies depending on which opioid they are stopping. For short-acting opioids like heroin and oxycodone, buprenorphine may be started 6-12 hours after the last dose. With longer-acting opioids such as morphine or extended-release preparations of oxycodone, buprenorphine should be delayed for about 24 hours. For the longest action opioids, fentanyl patch, 48 -72 hours must be between the last dose and buprenorphine initiation (3).

This initiation schedule means clients will be in the early stages of discomfort and withdrawal. Administration of buprenorphine when clients still have opioids in their bloodstream will lead to competition for receptor sites, rapidly replacing the opioid with buprenorphine and causing acute and more severe withdrawal symptoms.

Depending on the severity of a client's addiction, they may complete the first step of abstaining and withdrawal in an inpatient setting. Once the initial withdrawal symptoms have passed and the initial dose of buprenorphine has been given, the client may be discharged home to continue buprenorphine initiation on an outpatient basis (3).

Initial doses are typically 2-4mg, with up to 4mg given to clients used to higher potency or larger doses of opioids. The dose is gradually increased to meet the client's individual needs, with a maximum dosage of 24mg per day. The average client requires 8-12 mg per day and can reach this dose within the first 2-4 days. It is recommended that doses be supervised by a pharmacist at the dispensing pharmacy for the first two months of treatment to ensure compliance and clients are less likely to relapse (3).

The length of treatment with buprenorphine depends on each client's case and, for some, may be indefinite. Clients who do wish to wean off buprenorphine can begin the process once they are stable and experiencing few or no cravings, and a minimum of 8 weeks from treatment initiation. Doses are moved to alternating days and eventually discontinued altogether (3).

Side Effects and Contraindications:

As with any medication, there are potential side effects, including:

Common Side Effects

• Nausea
• Vomiting
• Drowsiness
• Dizziness
• Headache
• Memory loss
• Sweating
• Dry mouth
• Miosis
• Postural hypotension
• Sexual dysfunction
• Urinary retention

Serious side effects

• CNS depression
• QT prolongation
• Reduced seizure threshold
• Potential for abuse or overdose (3)

Buprenorphine is contraindicated for clients with a past hypersensitive reaction to it. It should be used cautiously for clients with respiratory suppression, older adults, or for those with liver pathologies. Regular monitoring of liver enzymes via lab work is essential (3).

It is a Category C medication for pregnancy, and the risks versus benefits should be carefully weighed. Buprenorphine does cross the placenta and increases the risk of withdrawal symptoms and neonatal abstinence syndrome (NAS) after delivery. However, for pregnant clients with the highest risk of relapse and abuse of opioids, evidence does support that continuation of buprenorphine during pregnancy may improve maternal and fetal outcomes (3).

Buprenorphine may be abused by crushing tablets, snorting the powder, or dissolving it into an injectable solution. Safety measures against this include supervised administration by a pharmacist and the addition of naloxone, which blocks the buprenorphine effects. While the effect ceiling of buprenorphine makes overdose difficult, combining the drug with benzodiazepines, alcohol, or other drugs can compound the CNS depressant effects and increase the risk of overdose (3).

Clinicians need to have a comprehensive health history of clients before initiating buprenorphine so that all risks and potential interactions can be addressed appropriately.

Role of the Pharmacist

Pharmacists play a significant role in the success of MAT involving buprenorphine. Outpatient doses are monitored by the dispensing pharmacist daily, with at-home quantities being allowed on a limited basis (such as weekends or travel) and only for the most motivated and compliant clients. Vital signs are collected before each dosage, with careful monitoring for hypotension or bradypnea. The dose may be skipped for clients who experience excessive side effects, and the client can return the next day for their dose.

Clients presenting with signs of overdose (usually to the ED) may receive naloxone, which will reverse overdose symptoms within 1 hour. Overdose symptoms include dizziness, pinpoint pupils, hypotension, bradypnea, hallucinations, seizure, or unconscious state.

If a client misses a dose, does not show up for it, or is experiencing significant side effects from buprenorphine, the prescribing clinician should be notified so that the treatment plan can be revisited and revised if needed (3).

Considerations for the Prescriber

When considering which medication to prescribe for MAT, prescribers should understand that buprenorphine offers advantages over methadone.

• Lower risk of abuse
• Safer, including at higher doses.
• Therapeutic dose achieved quickly.
• Easier to taper.
• Can be obtained from any provider rather than a methadone clinic.
• Less stigma

The cost of a 30-day supply is around $300. Buprenorphine/naloxone combinations are a little more expensive at $400/month. While prior authorization is usually required, most commercial insurance and state Medicaid programs will cover the medication.

Buprenorphine is a Schedule III Controlled Substance; however, recent federal regulations have been aimed at approving access to MAT, and any provider with an active DEA license may prescribe buprenorphine as allowed by state regulations. Specialized clinics are not required (as they are with methadone), and it is dispensed at regular pharmacies.

Prescribers are encouraged to participate in additional training about MAT with buprenorphine, but it is not required. Detailed documentation must be completed, including the reason for prescribing, start and end dates of treatment, the pharmacy used, the credentials of who will supervise administration, and frequency of follow-up and compliance monitoring. The sublingual and buccal routes are the only forms of medication used for MAT; patches, IM, and IV preparations are not routinely used for MAT.

The success of buprenorphine treatment depends on the client's education. Addiction potential, risk of combination with other CNS depressants, and side effects vs. signs of overdose should all be discussed with clients and their support system (3).

Methadone

Mechanism of Action and Metabolism

Methadone is a synthetic opioid and a full agonist of the Mu-receptor site, stimulating the same effects as opioids.

• Euphoria
• Analgesia
• Sedation

It can be used as a potent analgesic for pain not responding to traditional medications, such as in clients with cancer or terminal illness, as well as for MAT and neonatal abstinence syndrome (NAS).

For this course, it will be discussed as a MAT agent, used in treatment for clients addicted to opioids such as:

• Heroin
• Fentanyl
• Oxycodone
• Hydrocodone
• Morphine
• Hydromorphone (2)

Methadone is a full agonist at the Mu-receptor, meaning it is a more potent and more easily addictive medication than partial agonists like buprenorphine. Methadone has a long half-life (8-60 hours), occupying the Mu-receptors and blocking short-acting opioids from making a client high. The longer half-life also leads to less severe cravings and withdrawal symptoms. Methadone is also an antagonist to the N-methyl-d-aspartate (NMDA) receptor, which adds to its pain relief action (2).

It has high oral bioavailability, is active in the bloodstream within 30 minutes of ingestion and remains elevated for around 24 hours. It is broken down via CYP3A4 and CYP2B6 enzymes and metabolized through the liver, making it a good option for clients with renal problems.

Medications such as ciprofloxacin, benzodiazepines, fluconazole, cimetidine, and fluoxetine may slow methadone metabolism, increasing the available drug and the side effects of overdose risk. Other medications may speed metabolism and decrease the effects of methadone, including phenobarbital, phenytoin, rifampin, ritonavir, and carbamazepine (2).

Available Forms

Methadone is available in many forms, including oral, IM, subcutaneous, IV, and intrathecal, though only the oral is typically used for MAT.

• Methadone - tablets
• DISKETS - dispersible/dissolvable tablet
• Methadone HCL Intensol - 10mg/ml suspension
• Methadone - dispersible tablet (2)

Dosing and Monitoring

Oral dosing is initiated at 30-40 mg/day with a slow titration of 10-20 mg/week until the optimal dosage is reached. The optimal dosage varies by client and depends on the drug they are replacing, tolerance to opioids, and side effects experienced. A dosage between 80- 150 mg/day is the typical goal. (2)

If parenteral methadone is given, it is usually 50%-80% of the oral dosage.

Blood sugar, EKG, and methadone blood levels should be checked regularly, every week for higher-risk patients, and every 3-6 months for those in good health and compliance. The target methadone blood level is around 400 ug/ml (2).

Side Effects and Contraindications

Potential side effects are directly related to stimulation of the opioid receptors and include:

• Diaphoresis
• Flushing
• Pruritus
• Nausea
• Dry mouth
• Constipation
• Sedation
• Lethargy
• Respiratory Depression
• QT prolongation
• Hypoglycemia (2)

Methadone should be considered with a comprehensive view of a client's health history and other medications. Clients with CNS-related disease processes (trauma, increased ICP, dementia, or delirium) must be monitored closely or have other medication considered.

Methadone should not be used simultaneously as other opioids, benzodiazepines, alcohol, or antipsychotics due to increased CNS effects. Methadone is a Pregnancy Category C medication, and risks versus benefits should be weighed carefully. Infants exposed to methadone in utero are at increased risk of NAS after delivery (2).

Overdose can occur, and clients and support systems should be educated on signs of overdose.

• Lethargy
• Somnolence
• Stupor
• Coma
• Miosis
• Bradycardia
• Hypotension
• Respiratory sedation
• Cardiac arrest

Naloxone is used to reverse overdose (2).

Considerations for Prescribers and Clinics

Methadone is a Schedule II Controlled Substance, meaning it has a high abuse potential and must be carefully monitored. The Prescription Drug Monitoring Program (PDMP) is an electronic database used nationwide to register the distribution of controlled substances so that clients do not seek care at multiple clinics or pharmacies to obtain more of a controlled substance.

When prescribing methadone, providers should check the PDMP for both methadone and other prescription opioids so that they are fully aware of other medications clients may be receiving from other places. Regular urine drug screening should be performed to make sure clients are not using other substances not obtained by prescription and that they are testing positive for methadone, meaning they are genuinely taking it if administration is not observed (2).

At the beginning of treatment, methadone is given in the office under a nurse's supervision, and then clients are monitored for adverse effects. Some take-home doses (up to 7 in the first two weeks) may be arranged for weekends or during travel, but this possibility is limited during the first few weeks of treatment. As treatment progresses and compliance is demonstrated, clients may self-administer more doses at home (up to 28 doses per month) and go longer between visits to the clinic. The total length of treatment varies but is often 1-2 years and can even be indefinite (7).

There are methadone clinics that work entirely in the scope of addiction management, but primary care providers may prescribe methadone as well. Prescribers must have an active DEA license and comply with state-based controlled substance regulations (2).

Naltrexone

Mechanism of Action and Metabolism

Naltrexone has been in use since the 1960s and is an opioid antagonist. It competes primarily with the mu-receptor but also serves as an antagonist at the kappa and delta receptors. As an antagonist, it competes with agonists such as opioids and alcohol and blocks the effects of agonists at those sites.

• Prevents euphoria.
• Prevents intoxication.
• Reduces tolerance (6)

Naltrexone also acts on the hypothalamic-pituitary-adrenal axis, modifying it to reduce cravings and suppress alcohol consumption.

It is FDA-approved for use in clinical practice for the treatment of:

• Alcohol use disorder
• Opioid use disorder (prescription and non)

Naltrexone is absorbed orally and undergoes extensive metabolism via the first-pass effect. However, this does not affect its potency as naltrexone's active metabolite, 6β-naltrexone, acts as a potent opioid antagonist. The medication's half-life is around 4 hours but can last up to 24 hours. If administered parenterally, it bypasses the first pass and is even longer acting, with a half-life of 5-10 days. Naltrexone is excreted by the kidneys (6).

Available Forms

Naltrexone is available in an oral tablet and IM injection. Available preparations include:

• Generic naltrexone tablets
• Revia (oral tablet)
• Depade (oral tablet)
• Vivitrol (solution for IM injection, extended-release) (6)

Dosing and Monitoring

Since naltrexone will compete for and block all opioid receptor sites, the risk for withdrawal symptoms is high, and clients must stop the use of alcohol or opioids for 7-10 days before beginning treatment to lessen the risk of withdrawal symptoms. A naltrexone challenge is recommended at the start of therapy.

This consists of administering small amounts of naltrexone subcutaneously or via IV and monitoring the client and their vital signs for signs of withdrawal, such as:

• Nausea
• Vomiting
• Diaphoresis
• BP changes
• Tachycardia
• Rhinorrhea
• Agitation
• Tremors
• Abdominal pain
• Pupillary dilation (6)

If a client fails the naltrexone challenge and has not been long enough since their last use of alcohol or opioids, the naltrexone initiation should be delayed, and the test should be repeated in 24 hours. If clients tolerate the naltrexone test and the negative result, they may begin naltrexone treatment (6).

For oral tablets, dosing usually starts at 25 mg for the first dose. Clients are observed for withdrawal symptoms and side effects; an additional 25 mg is given 1 hour later. After that, clients take 50 mg per day. Clients may continue with 50mg daily or take 100 mg every other day or 150 mg every 3rd day (6).

Alternatively, naltrexone may be given via IM injection for more extended action, improving compliance and reducing relapse. Particularly for alcohol or heroin dependence, data indicates that the IM route has much higher success rates than the oral route. If a client receives the IM injection, 380 mg is given to the gluteal muscle every four weeks (6).

Side Effects and Contraindications

Most common side effects of naltrexone include:

• GI irritation
• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Hypertension
• Headache
• Anxiety
• Low energy
• Joint or muscle pain
• Nervousness
• Sleep disruption

Less commonly, clients report:

• Loss of appetite
• Constipation
• Dizziness
• Irritability
• Depression
• Rash
• Chills (6)

Caution should be used for clients with liver function issues and renal impairment. It is Category C for use during pregnancy, and the risks versus benefits of use in pregnancy must be carefully considered. It also crosses into breast milk and must be considered carefully.

There is limited data about the overdose of naltrexone, and there may be very few symptoms if an overdose occurs. Clients should be monitored for signs of liver dysfunction, seizures, depression, and suicidal ideations. No antidote for naltrexone is currently available.

Naltrexone is contraindicated for clients who failed a naltrexone challenge, test positive for opioids or alcohol on drug screening, have a history of seizures, or have experienced a past hypersensitivity reaction to naltrexone.

Clients may switch from buprenorphine or methadone to naltrexone at some point in treatment. Both medications are agonists at the opioid receptor sites, so changing to naltrexone (an antagonist) may increase the risk of withdrawal symptoms for the first two weeks of treatment (6).

Considerations for Prescribers

Because naltrexone does not cause any euphoria or "high," the abuse potential is non-existent. It is not a controlled substance and can be prescribed by any clinician with prescriptive authority. However, its use is typically only by those who work in mental health or addiction medicine. Clients can take the medication at home or go to the clinic for IM injections.

Many considerations for naltrexone use center around monitoring for side effects and treatment compliance. Baseline and periodic drug screening and liver function tests are prudent. Clients' support persons should be educated on compliance and signs of relapse. The IM formulation should be considered for those with poor compliance or most at risk for relapse (6).

Nursing Considerations

Nurses will encounter clients with addiction and even those receiving MAT in a variety of settings, including:

• Outpatient clinics for routine care of any health issues
• ED admission for acute problems not related to addiction.
• Inpatient hospitalization related to other health problems.
• Outpatient setting for participation in MAT or addiction management.
• ED admission for acute problems related to substance abuse or toxicity of MAT medication.
• Inpatient mental health admission for mental health and addiction issues

Regardless of the setting and if the client is being seen for an addiction issue or something else, it is crucial for nurses to be familiar with MAT medications and how they work to provide safe and competent care. Nurses may need to:

• Administer medication.
• Monitor lab results.
• Observe for side effects, toxicity, or withdrawal symptoms.
• Coordinate care within a multidisciplinary team
• Communicate with therapeutic and nonjudgmental techniques.

Case Study

Justin is a 32-year-old male who presents to the ED with nausea, lethargy, and confusion worsening over the last 24 hours. Upon exam, the nurse notes diaphoresis, slurred speech, and pinpoint pupils. His vitals are RR 10, HR 54, BP 82/58, SPO2 97%, Temp 99.0.

He reports taking Wellbutrin 150mg daily for depression and smoking cessation, methadone 100mg daily for history of oxycodone abuse, and was started on ciprofloxacin 250mg BID for a UTI 2 days ago at urgent care.

His labs are significant for a WBC of 15,000 but otherwise regular. He tests positive for methadone, which is expected, but not for other substances. He reports being compliant with MAT and avoiding opioid use for nine months.

It is determined that Justin is experiencing methadone toxicity due to the slowed metabolism of the drug from the combination of methadone and ciprofloxacin. He is given naloxone in the ED, and within an hour, his symptoms have improved significantly, and his vital signs are typical. His antibiotic is switched to cefdinir, and he is discharged home in stable condition with instructions to follow up with his PCP within 1-2 days.

Conclusion

Substance use disorders are a long-standing and dangerous pathology experienced by millions of people each year. At the same time, the stigma of seeking help for such disorders has been eroding in recent years; there has also been a renewed push by the federal government to address the issue in evidence-based and meaningful ways, with access to effective treatment being at the top of the priority list.

Addiction treatment programs utilizing MAT will likely become much more popular in the coming years, and nurses will be on the front lines of this therapy. For nurses to provide competent and comprehensive care to this client population, up-to-date and accurate knowledge is necessary.

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