Best practice

This chapter explores the potential for medications to assist in the treatment of substance misuse and substance use disorders. Two general terms or labels are applied to this kind of intervention strategy: pharmacotherapy and and medication assisted treatment (MAT). The underlying assumption is that substance use disorders and addiction are diseases of the brain and brain chemistry, therefore addressing those brain chemistry mechanisms is a reasonable approach to treatment. Furthermore, pharmacotherapy is intended as a means of supporting the transition from substance misuse to substance abstinence through medication assistance the helps individuals overcome cravings and withdrawal (short- and long-term).

Medications are considered a best practice treatment for opioid use disorders and can be used to treat alcohol and nicotine use disorders as well.  Additionally, medications can be used 

• during an acute opioid overdose to attempt to prevent death
• to reduce opioid, alcohol and tobacco cravings
•  during the detoxification process for a variety of substances
•  to treat physical or mental health conditions co-occurring with misuse of a variety of substances
• to treat chronic and acute pain

Medication to attempt to reverse an opioid overdose

One of the most critical uses of medication is during an acute opioid overdose. Naloxone (Narcan® or Evzio®) can be administered in an effort to decrease the chances of a fatal overdose. As an opioid antagonist, naloxone binds to opioid receptors in the body and blocks the opioid’s effects. The amount of opioid reversal drug needed depends on the dose and strength of the opioid involved in the overdose event. This means the overdose reversal drug needs to be available, available in a quantity sufficient for managing the overdose event, and someone needs to be able to administer it in the event of overdose. It is important to note that naloxone can not be self-administered. The opioid overdose reversal drug puts the person into immediate withdrawal, which is exactly what the person may have been using the opioids to avoid. It can be life-saving when it can restore normal breathing suppressed by an opioid overdose. Many communities and institutions have adopted naloxone distribution programs, policies, and Good Samaritan laws allowing lay persons on the scene to administer the overdose reversal care before professionally trained first responders can do so and making it easier for individuals to obtain and carry a reversal kit for use in the event of an overdose. Ideally, an overdose incident can be followed up with outreach efforts designed to engage the individual in OUD treatment—handling the event as a “reachable” moment. It is important to note that naloxone is not effective in reversing all overdoses.  Death can still occur. It is considered a best practice to encourage people at risk of an opioid overdose to have naloxone readily available.  

Medications to manage pain

One in five US adults have had chronic pain lasting at least 3 months (Dahlhamer et a., 2018), and six percent of adults take opiates to manage their pain (Frenk et al., 2019); correspondingly, patient pain needs to be managed or a patient risks turning to self medication with illicit drugs (HHS, 2019).  The goal is to use a combination of non pharmacological supports such as cognitive behavioral therapy, relaxation techniques, sleep hygiene, exercise, mindfulness, and if needed, pharmacological supports to decrease patient pain while also reducing risk of addiction or relapse of active addiction.  Anti-depressant medications and non-opioid analgesics such as acetaminophen, NSAIDs gabapentin, pregabalin, topical lidocaine may be appropriate and sufficient.  Sometimes opiates are necessary.  When indicated, patients should be referred to a pain management specialist skilled in working with patients with substance use disorder history (HHS, 2019). Urine drug testing, abuse deterrent formulations, and smaller quantity prescriptions with frequent follow ups may be indicted.

Medication assisted detoxification/stabilization 

Detoxification (detox) is part of the continuum of care in addressing a person’s substance misuse or substance use disorder and may involve an interdisciplinary team.

According to TIP #45 (CSAT, 2006):

“Detoxification is a set of interventions aimed at managing acute intoxication and withdrawal. It denotes a clearing of toxins from the body of a patient who is acutely intoxicated and/or dependent on substances of abuse. Detoxification seeks to minimize the physical harm caused by the abuse of substances” (p. 4).

The TIP #45 resource also explains that the detoxification process is comprised of 3 essential components:

• Evaluation (e.g., person’s physical and mental status, types and amounts of substances involved)
• Stabilization (establish safe physical and mental status)
• Fostering readiness for engaging in treatment.

Pharmacotherapy and MAT might assist in the detox and stabilization processes: “This often is done with the assistance of medications” (CSAT, 2006, p. 4). Medically supervised detoxification is an important means of managing potentially life-threatening withdrawal and other physical (or suicidality) concerns that may arise during this early step in recovery. The length of time required to complete detoxification and stabilization varies as a function of the drugs and doses involved, as the persistence of different substances being metabolized varies markedly. Detox and stabilization are not considered a completed substance misuse treatment episode but an important component that also provides a person with: “a point of first contact with the treatment system and the first step to recovery. Treatment/rehabilitation, on the other hand, involves a constellation of ongoing therapeutic services ultimately intended to promote recovery” (CSAT, 2006, p. 4).

A detox/stabilization program may consist of specific stages or phases with different aims at each point in the process (CSAT, 2006).

The initial goal is to monitor any acute medical situation or crisis, ensuring safety as the misused substances leave the body (withdrawal). Administering medications to support the person medically could take place during this phase, but only if the stabilization team knows what substances were involved—a polydrug misuse crisis might leave the team unwilling to risk administering medications that might adversely interact with some of the potentially involved substances. The second phase of stabilization involves a more extended detoxification treatment plan (measured in days) to manage the early withdrawal period and to support the person in obtaining ongoing treatment for their substance misuse/substance use disorder. This might involve a medication assisted treatment (MAT) plan. The third phase of a stabilization plan might continue for days to weeks with the goal of supporting the person in making a successful transition to long-term treatment, often involving counseling, supportive recovery services (e.g., sober housing and other case management services), and MAT.

Sedative-Hypnotic/CNS Depressant Use Disorder. The withdrawal process for sedative-hypnotics/CNS depressants can be complicated and potentially deadly, therefore withdrawal may best be managed with close medical supervision and management (CSAT, 2006). The pharmacotherapy medication of choice for sedative-hypnotic/CNS depressant withdrawal has been benzodiazepine—another sedative-hypnotic/CNS depressant. This intervention approach is based on transitioning from the effects of one CNS depressant (e.g. alcohol or other CNS depressant) to another (benzodiazepine), then imposing a more controlled physical withdrawal process through gradual tapering of the second CNS depressant (the benzodiazepine; CSAT, 2006).

Medication to reduce craving, withdrawal and illicit use in opioid use disorder

Treating opioid use disorder (OUD) often involves prescribed medications as part of an evidence-based intervention plan—medication assisted treatment (MAT). Three medications have been approved by the U.S. Food and Drug Administration (FDA) for this purpose and have a strong evidence base supporting their use: methadone (itself a synthetic opioid), buprenorphine (an opioid partial agonist), and naltrexone (an opioid antagonist). Additional medications are in trial for treating OUD, as well (Portelli, Munjal, & Leggio, 2018). These medications work on the same brain opioid receptor systems affected by opioid misuse—humans naturally have opioid receptors in the brain and some other parts of the body.

The distinction between agonist and antagonist medications is relevant to pharmacotherapy intervention strategies. An agonist leads to activation or stimulation of neurons when it binds to the specific receptor sites, and an antagonist blocks (or dampens) the neurons’ responses when it binds to the specific receptor sites (Portelli, Munja, & Leggio, 2020). This information helps determine which medications are most likely to produce the desired effect in treating misuse of a specific type of substance. Different drugs even within the same class have different rates at which they are absorbed and metabolized, and dosing is dependent on finding the medication’s therapeutic zone without moving into an overdose level where side effects outweigh the benefits. A person may develop physical dependence on some pharmacotherapy/MAT medications, just as they did to the misused substances, that tolerance to some pharmacotherapy agents may develop, and that withdrawal from some of these medications may be unpleasant. Critical in all of this discussion is medication management (MM)—ensuring that a person has access to the medications prescribed, is able to and does use them as prescribed, and is able to tolerate the side effects (e.g., see Medication Management Support for Alcohol Dependence, (https://pubs.niaaa.nih.gov/publications/clinicianGuide/guide/tutorial/data/resources/MedMgmtSupportTemplates.pdf).

As SAMHSA has outlined (https://www.samhsa.gov/medication-assisted-treatment), medications can be used to decrease cravings, decrease symptoms of withdrawal, block the euphoric effects of illicit drugs, and manage chronic pain. Like any medication, there are advantages and disadvantages to their use. The success rates in retaining individuals in opioid use disorder treatment and reducing the illicit use of opioids is greater with medication assisted treatment than without (and better than placebo), and MAT (plus counseling) is more cost-effective than treatment without medication. Patients who use MAT are more likely to obtain and sustain employment and most importantly, patients who take medication are more likely to stay alive (https://www.samhsa.gov/medication-assisted-treatment). Criminal activity, infection and the spread of disease is reduced, and pregnant women who use medication to treat opioid use disorder have better birth outcomes (https://www.samhsa.gov/medication-assisted-treatment). According to SAMHSA, “These MAT medications are safe to use for months, years, or even a lifetime” (https://www.samhsa.gov/medication-assisted-treatment).  Despite this mounting evidence, medication in treating opioid use disorder currently is grossly underutilized (Portelli, Munjal, & Leggio, in press). The Substance Abuse and Mental Health Services Administration, in its Treatment Improvement Protocol (TIP) #63 (SAMHSA, 2018), and Portelli, Munjal, and Leggio (in press) compared these three options for medication assisted treatment (SAMHSA, 2018).

Methadone. Methadone is used both in medically supervised withdrawal from opioids (short-term) and longer-term recovery maintenance. It is a Schedule II controlled substance, having addictive potential itself, and is generally only legally distributed through specially licensed/federally certified opioid treatment programs or inpatient hospital settings treating opioid use disorder. Methadone maintenance therapy (MMT) which combines medication and counseling is the primary and most researched approach to use of methadone in treating OUD.

Compared to heroin which is taken multiple times per day to avoid withdrawal symptoms, methadone is longer acting, so that it is dosed once daily. This creates a more even psychoneurological experience of withdrawal which supports opioid abstinence goals. As an agonist, it creates some of the same effects as opioids/heroin (respiratory depression, sedation, heart rhythm changes, low blood pressure, constipation), but in a more controlled dosing pattern and at a level insufficient to create a “high” when used as prescribed. Methadone “helps individuals experiencing OUD reduce withdrawal symptoms and craving for opioids by delivering the desired drug effect over a longer period than the abused substances” (Portelli, Munjal, & Leggio, in press). Pharmaceutical-grade methadone is more predictable, and when used correctly, safer than illicit substances. Methadone can be gradually tapered off to eventually leave a person opioid-free or can be maintained indefinitely.  Methadone is known to reduce risk of overdose-related death, as well as harms associated with illicit opioid misuse such as HIV/Hepatitis infection and criminal activity (SAMHSA, 2018). Because of its effectiveness, the World Health Organization (WHO) “lists it as an essential medication” (SAMHSA, 2018). Methadone maintenance programs often engage recipients in other recovery-support services.

Methadone is considered a safer alternative to illicit opioids for opioid use disorder management during pregnancy since it reduces the occurrence/cycles of withdrawal which pose a significant risk to the fetus and viability of the pregnancy (causing premature labor contractions, among other risk events). However, the baby has a high likelihood of experiencing neonatal withdrawal syndrome (NWS) at birth and will need to be weaned off the methadone just as in the case of any other opioid.

Buprenorphine. Buprenorphine is used both in medically supervised withdrawal from opioids (short-term) and longer-term recovery maintenance. It is a Schedule III controlled substance originally introduced for pain management. It may be prescribed outside of federally certified opioid treatment programs by professionals with a prescribing waiver, distributed by a pharmacy, making it more easily accessible than methadone. As a partial agonist, buprenorphine has some of the same effects as opioids (respiratory depression) without creating the “high” when used as prescribed, but it also may precipitate some degree of opioid withdrawal symptoms (nausea, sweating, insomnia, pain). For this reason, adhering to the treatment may be more difficult than with methadone. Buprenorphine does have some addictive potential but less so than methadone. Risks are greater when combined with use of other drugs that affect breathing (e.g., benzodiazepines). It can be delivered by monthly injection as a slow-release option is available. Naloxone (an opioid antagonist that precipitates opioid withdrawal symptoms and used in opioid overdose reversal) is sometimes combined with buprenorphine to help prevent its misuse. Buprenorphine allows for gradual tapering to eventually no longer needing opioids or medication to manage withdrawal. Because of its effectiveness, the World Health Organization (WHO) “lists it as an essential medication” (SAMHSA, 2018). Buprenorphine may cause neonatal withdrawal syndrome (NWS) but is considered safer than alternatives—however, pregnant women may be less likely to remain in buprenorphine treatment than with methadone, which increases risks to the fetus and pregnancy (see CSWE course, America’s Opioid Crisis).

Naltrexone. Naltrexone is used in opioid use disorder relapse prevention after medically supervised withdrawal. As an opioid antagonist, it blocks opioid receptor sites, acting in a longer-acting manner but similarly to the overdose reversal drug, naloxone. Thus, Naltrexone minimizes the rewarding effects of opioid use, but also can precipitate opioid withdrawal. It requires a prescription but is available through primary care providers without specialty waivers or certification as an opioid treatment program. It does carry a risk of potential side effects (nausea, anxiety, depression, insomnia, liver toxicity, suicidality, sedation, loss of appetite, dizziness, muscle cramping). In addition, because it can precipitate withdrawal, it reduces pre-existing tolerance so that if a person relapses to using opioids, the risk of overdose is increased. Naltrexone in a monthly injectable form was equally effective to oral buprenorphine in maintaining post-withdrawal opioid abstinence in one study, and in another, showed a lower rate of relapse than no medication (SAMHSA, 2018).

Medications to treat alcohol use disorder

Alcohol withdrawal can be a complicated, and potentially deadly, process best managed with close medical supervision and management (CSAT, 2006). While the majority of individuals will not need medication to manage the stabilization process following alcohol intoxication, medications might be helpful for the others (CSAT, 2006).

Benzodiazepine has a significant history as a first step in treating alcohol withdrawal (Zweben & West, 2020), but benzodiazepine treatment also introduces significant risks of its own (CSAT, 2006). Three medications used in longer-term treatment of alcohol misuse/use disorder and relapse prevention are not particularly addictive themselves and are otherwise reasonably safe to use: naltrexone, acamprosate, and disulfiram (Portelli, Munja, & Leggio, 2020).

Naltrexone was approved by the FDA in 1994 for treatment of alcohol use disorder (Suh, Pettinati, Kampman, & O’Brien, 2006). Naltrexone is an opioid receptor antagonist that decreases the positive reinforcing effects of alcohol use, thereby gradually reducing a person’s craving for alcohol as the reward is not as strongly “paired” with the behavior (Suh et al., 2006). Adherence with naltrexone therapy is bolstered by using a long-acting, extended-release injectable form (e.g. Vivitrol®) instead of a daily oral dosing protocol (Portelli, Munjal, & Leggio, 2020).

Acamprosate became an FDA-approved alcohol use disorder treatment medication in 2004 (Suh et al., 2006). It works at the neurotransmitter level, reducing the longer-term negative withdrawal effects of quitting alcohol use—effects associated with relapse, making it easier to stick with a recovery commitment. One of the benefits of acamprosate over some other medications: it is not metabolized by the liver which is important in persons whose liver may be compromised from chronic alcohol misuse or who might have hepatitis or other liver disease (Witkiewitz, Saville, & Hamreaus, 2012). It is also a safely tolerated alternative for a person whose treatment goal is to reduce their drinking but not eliminate all alcohol use (Witkiewitz, Saville, & Hamreaus, 2012).

In 1951, disulfiram (Antabuse®) was approved by the FDA for use in treating alcohol use disorder (Suh et al., 2006). This drug works differently from the previous two: it creates a set of acute physical discomforts when alcohol is consumed in its presence. In learning theory terms, drinking behavior is punished by the physical consequences experienced. It does this by inhibiting the enzyme (ALDH, aldehyde dehydrogenase) responsible for metabolizing the first-order alcohol metabolite, acetaldehyde, thus allowing the acetaldehyde to build up to levels where facial flushing, sweating, headache, nausea/vomiting, rapid and/or irregular heart rate occur soon after drinking alcohol (Suh et al., 2006). Pharmacotherapy with disulfiram for treating alcohol use disorder can be somewhat tricky and complicated. For example, the individual needs to be sufficiently motivated for change and have reliable access to the medication in order to take the medication as prescribed (medication adherence); skipping doses means they can drink again without the immediately punishing consequences. Dosing is also an issue, as the aim is to cause mild discomfort rather than significant symptoms when alcohol is consumed, but these consequences are alcohol dose dependent (Suh et al., 2006). The unpleasant reaction may even be triggered by exposure to alcohol in other forms, such as: alcohol-based hand sanitizer, mouthwash, cleaner, or solvent; cooking wine or wine-based vinegar; flamed/flambé desserts using alcohol as the fuel; and more. Like any medication, it is not without side effects, but these are generally considered mild (Suh et al., 2006). 

For in-depth information about the the use of medication in alcohol use disorder please see https://store.samhsa.gov/product/Medication-for-the-Treatment-of-Alcohol-Use-Disorder-A-Brief-Guide/SMA15-4907.

Medications to treat nicotine addiction

Tobacco use disorder has greater chances for successful treatment when pharmacotherapy and behavioral therapies are delivered in combination (Portelli, Munjal, & Leggio, 2020). Among the pharmacotherapy strategies are nicotine replacement therapy (NRT) and medications that influence neurotransmitter systems. NRT options include various forms of administering controlled doses of nicotine (the most addictive of the chemicals in tobacco use: transdermal (skin) patches, gum, lozenges, oral/nasal spray, or inhaler (e.g, vaping). “There exists robust evidence of the efficacy of NRTs in aiding smoking cessation” (Portelli, Munjal, & Leggio, 2020, p. 327). Bupropion (e.g., Zyban®) acts on nicotine withdrawal effects, making it easier to avoid relapse. Varenicline (e.g. Chantix®) acts by mildly stimulating the same receptor sites activated by nicotine and, at the same time, blocks nicotine’s dopamine releasing capabilities—in other words, it is both an agonist and antagonist medication. Thus, it provides some of the reinforcement previously gained with smoking cigarettes and decreases the reinforcement received from smoking again. Evidence supporting e-cigarettes/vaping as an NRT is mixed: evidence suggests that individuals can effectively use this method to taper off of cigarette smoking, however it is all too common that they simply replace smoking cigarettes with continued e-cigarette use and fail to taper off the nicotine and remain addicted (Portelli, Munjal, & Leggio, 2020). There exist significant health and safety concerns related to e-cigarette use.

Considerations

Medications used to treat substance use disorders are not without side effects and risks themselves: some pharmacotherapy medications have addictive potential (e.g., methadone), and some can cause dangerous even deadly side effects. The hope is that their known risks can be managed more safely than in the uncontrolled world of illicit substance misuse. In other words, use of managed, monitored, medication assisted treatment is a form of harm reduction strategy.

MAT or pharmacotherapy is a tool in the collection of options available for the treatment of substance use disorders. The science surrounding the development and testing of new medication applications changes rapidly, so new medications may come into favor just as older and current medications may decline in favor as treatment approaches (Portelli, Munja, & Leggio, 2020). No one-size-fits-all approach works for everyone. Like any treatment program, pharmacotherapy/MAT needs to be tailored to individuals and their circumstances, and often need to be modified as a person’s circumstances change over time. Furthermore, many individuals engaged in polydrug use or experiencing co-occurring problems may need individualized medication regimens as different medications used in pharmacotherapy/MAT have differing effects, differing effectiveness for addressing misuse of different substances, and interact differently with conditions and other medications (Portelli, Munja, & Leggio, 2020).