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Pharmacotherapies for Substance Use Disorders

Opioid Use Disorder

Opioids include prescription drugs such as hydrocodone (Vicodin®), oxycodone (OxyContin®, Percocet®), codeine, and morphine, as well as illegal substances like heroin. Over the last decade, prescription opioids have been increasingly prescribed to treat and manage acute and chronic pain. The use of opioids can lead to dependence, and in cases of misuse or overdose, severe respiratory depression and even death.

Prescription opioids can be beneficial for pain management and can be legally prescribed. Although opioids can be highly addictive, not everyone will develop harmful or problematic behaviors around using these medications to manage pain. In March 2016, the Centers for Disease Control and Prevention (CDC) published the CDC Guideline for Prescribing Opioids for Chronic Pain, which summarizes the risks and benefits associated with prescription opioids and provides an evidence-based guide for clinicians and patients in shared decision-making about the use of prescription opioids. Additionally, Prescription Drug Monitoring Programs, discussed in the Harm Reduction section of this Module, are an effective method of sharing information among healthcare providers about opioid prescriptions and possible instances of misuse.

Three medications have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of opioid dependence: methadone, buprenorphine, and naltrexone. These medications are effective for treating people with opioid use disorders, as well as legally prescribed opioid pain relievers that are misused, such as oxycodone, hydrocodone, and morphine. The medications work by easing withdrawal symptoms from opioids and blocking its euphoric effects.

  • Methadone: Methadone has been used since the 1960s for the treatment of opioid use disorders by reducing cravings and preventing withdrawal symptoms. Patients who take methadone must receive the medication while under physician supervision and the medication can only be dispensed through an opioid treatment program certified by the Substance Abuse and Mental Health Services Administration (SAMHSA). SAMHSA provides prescribing courses for physicians, as well as other webinars and workshops. Demand for methadone treatment often exceeds availability, leading to extensive waitlists. One methadone clinic in rural Vermont reported a waitlist of over 900 people, which meant an approximate 1.9-year delay in accessing methadone treatment. Methadone maintenance treatment has demonstrated a $2.28 return on investment for every dollar spent.
  • Buprenorphine: Buprenorphine allows for the reduction or elimination of withdrawal symptoms that can accompany the discontinuation of opioids. The benefit of buprenorphine is that, unlike methadone treatment, buprenorphine can be prescribed or dispensed by certified healthcare providers in clinics, community hospitals, health departments, or a correction facility, making it a more accessible treatment option. Buprenorphine is closely regulated, and healthcare providers must qualify for a waiver in order to prescribe the medication. In order to qualify for a waiver, the healthcare provider must receive certification and training on the dispensing of this medication for the treatment of opioid use dependency. The Comprehensive Addiction and Recovery Act of 2016 included a provision that, for the first time, allows not only physicians but also physician assistants and nurse practitioners to prescribe buprenorphine. SAMHSA provides extensive information on certifications and trainings, as well as buprenorphine waiver management. Additionally, SAMHSA's Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction provides guidelines for physicians in screening, assessing, and treating opioid use disorder with buprenorphine. Buprenorphine can be administered as sublingual tablets, injection, transdermal patch, or in a combination formulation with naloxone. In May 2016, the FDA approved Probuphine, the first implantable buprenorphine for the treatment of opioid dependence. Implantable buprenorphine may help with treatment adherence as well as prevent the stealing and misuse of tablet or film forms of the medication. Buprenorphine (Suboxone and Subutex) treatment has demonstrated a benefit to cost ratio of $1.81 (in benefits for every dollar spent).
  • Naltrexone: Unlike methadone and buprenorphine, naltrexone is an opioid antagonist, which means it works by blocking opioid receptors and preventing their euphoric effects. While it can help reduce cravings, naltrexone should only be used seven to ten days after medically managed withdrawal (detoxification) from opioids has been completed. Naltrexone can be prescribed by any healthcare provider licensed to prescribe medications. It does not require special training like buprenorphine and methadone. Naltrexone can be delivered as a daily oral dose or as a long-acting injection. The long-acting injection only needs to be administered once per month, which has shown an increase in adherence and retention rates.

Alcohol Use Disorder

Excessive alcohol consumption increases the risk of serious health conditions such as heart disease, brain and liver damage, and hypertension and can cause health issues related to intoxication behaviors and withdrawal. To be diagnosed with alcohol use disorder, individuals must meet certain criteria such as being unable to control alcohol intake, developing a tolerance, and/or developing withdrawal symptoms.

There are three medications approved by the FDA for the treatment of alcohol use disorder: acamprosate, disulfiram, and naltrexone. These medications work in different ways and are most effective when used in combination with behavioral therapies as part of a comprehensive treatment plan.

  • Acamprosate: Acamprosate is a medication that works on neurotransmitters and reduces the symptoms of withdrawal. This medication helps patients to maintain abstinence from alcohol for longer periods of time.
  • Disulfiram: Disulfiram is a medication that changes the way the body metabolizes alcohol. The resulting changes lead to unpleasant reactions when alcohol is consumed, including nausea and palpitations.
  • Naltrexone: Naltrexone, also used in the treatment of opioid use disorder, can be used to reduce cravings for alcohol among those with alcohol use disorder. It is also used to block the rewarding effects of intoxication but does not react adversely when used with alcohol.

Examples of Pharmacotherapy Models

Project Lazarus, which began in Wilkes County, North Carolina, has created a series of toolkits designed for care managers, primary care providers, and emergency department staff about opioid use disorders. The Project Lazarus training addresses common misconceptions about opioid use disorders and addresses resistance of some providers to prescribing medication-assisted treatments. The program encourages healthcare providers to obtain buprenorphine waivers and provide this treatment option in their communities.

Considerations for Implementation

Buprenorphine and methadone are opioids; these treatment options are sometimes viewed as a method of replacing one addictive substance for another. However, under the supervision of healthcare providers certified to dispense the medications, these drugs can reduce and eliminate withdrawal symptoms and reduce the high-risk behaviors often associated with drug use, particularly injection drug use. In addition to reducing risk behaviors, these medications can increase retention rates for treatment.

One study in The American Journal of Drug and Alcohol Abuse found that rural treatment centers were less likely to prescribe buprenorphine, which could indicate that there may be opportunities for provider education on its benefits. A study from the Annals of Family Medicine using data from multiple sources on physician waivers for buprenorphine found that of the counties reporting no physicians who could prescribe buprenorphine, 82.1% were rural counties. As a result, rural residents must travel long distances to receive treatment. Buprenorphine may have especially beneficial outcomes in rural communities where there is opposition to the establishment of methadone clinics or where transportation barriers prevent patients from accessing the methadone clinic. Even among prescribers who have obtained the SAMHSA waiver for prescribing buprenorphine, certified providers may only treat 30 patients at a time in the first year, followed by up to 100 patients in subsequent years. Although a final rule published in July 2016 increased access to buprenorphine by increasing treatment caps for eligible providers to up to 275 patients annually, it still may not be adequate to meet the growing demand for the medication.

Ideally, medication-assisted treatment is provided in coordination with behavioral therapy or counseling. The National Institute on Alcohol Abuse and Alcoholism has found that the treatment of alcohol use disorder with pharmacotherapies is most effective when combined with some type of behavioral therapy. Behavioral therapies are also discussed in this toolkit.

Program Clearinghouse Example

Resources to Learn More

Buprenorphine Treatment Physician Locator
Directory of physicians authorized to dispense buprenorphine by state.
Organization(s): Substance Abuse and Mental Health Services Administration

Guideline Resources
Contains resources on opioid use as it relates to chronic pain. Resources include information for clinicians and patients, trainings, graphics, and other tools.
Organization(s): Centers for Disease Control and Prevention

Implementing Medication-Assisted Treatment for Opioid Use Disorder in Rural Primary Care: Environmental Scan
This two-part report provides a comprehensive overview with the unique opportunities and challenges, as well as innovative models, for implementing Medication-Assisted Treatment (MAT) in a rural primary care setting. It also includes almost 250 tools and resources that can be used by providers, patients, and public health for implementing MAT.
Organization(s): Agency for Healthcare Research and Quality
Date: 10/2017

Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
A guide designed for healthcare practitioners which provides direction on screening, assessing, and treating patients with an alcohol use disorder.
Organization(s): Substance Abuse and Mental Health Services Administration, National Institute on Alcohol Abuse and Alcoholism
Date: 10/2015

National Institute on Alcohol Abuse and Alcoholism
Provides numerous resources on alcohol use disorder, including funding opportunities, video conferences, and education materials for health professionals.
Organization(s): National Institute on Alcohol Abuse and Alcoholism

Overview of Medications for Addiction Treatment
A collection of educational resources and training modules for healthcare providers providing opioid use disorder pharmacotherapy treatment.
Organization(s): Providers Clinical Support System

National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use
A collection of best-practice guidelines created for primary care providers using medication-assisted treatment for treating opioid use disorders.
Organization(s): American Society of Addiction Medicine
Date: 06/2015