National Institute on Drug Abuse (NIDA): Medications to Treat Opioid Use Disorder

Opioid Agonists and Partial Agonists (Maintenance Medications)

Studies show that people with opioid use disorder who follow detoxification with complete abstinence are very likely to relapse, or return to using the drug. Although relapse is a normal step on the path to recovery, it can also be life-threatening, raising the risk for a fatal overdose. Thus an important way to support recovery from heroin or prescription opioid use disorder is to maintain abstinence from those drugs. Someone in recovery can also use medications that reduce the negative effects of withdrawal and cravings without producing the euphoria that the original drug of abuse caused. For example, the US Food and Drug Administration (FDA) recently approved lofexidine, a nonopioid medicine designed to reduce opioid withdrawal symptoms. Methadone and buprenorphine are other medications approved for this purpose.

Methadone is a synthetic opioid agonist that eliminates withdrawal symptoms and relieves drug cravings by acting on opioid receptors in the brain—the same receptors that other opioids such as heroin, morphine, and opioid pain medications activate. Although it occupies and activates these opioid receptors, it does so more slowly than other opioids and, in an opioid-dependent person, treatment doses do not produce euphoria. It has been used successfully for more than 40 years to treat opioid use disorder and must be dispensed through specialized opioid treatment programs.

Buprenorphine is a partial opioid agonist , meaning that it binds to those same opioid receptors but activates them less strongly than full agonists do. Like methadone, it can reduce cravings and withdrawal symptoms in a person with an opioid use disorder without producing euphoria, and patients tend to tolerate it well. Research has found buprenorphine to be similarly effective as methadone for treating opioid use disorders, as long as it is given at a sufficient dose and for sufficient duration. ⁶⁵ The FDA approved buprenorphine in 2002, making it the first medication eligible to be prescribed by certified physicians through the Drug Addiction Treatment Act. This approval eliminates the need to visit specialized treatment clinics, thereby expanding access to treatment for many who need it. In addition, the Comprehensive Addiction and Recovery Act (CARA), which was signed into law in July 2016, temporarily expands eligibility to prescribe buprenorphine-based drugs for medication-assisted treatment (MAT) to qualifying nurse practitioners and physician assistants through October 1, 2021. Buprenorphine has been available for opioid use disorders since 2002 as a tablet and since 2010 as a sublingual film, and the FDA approved a 6-month subdermal buprenorphine implant in May 2016. This formulation is available to patients stabilized on buprenorphine and will eliminate the treatment barrier of daily dosing for these patients. (Also see “What Are Misconceptions About Maintenance Treatment?”)

Opioid Antagonists

Naltrexone is an opioid antagonist , which means that it works by blocking the activation of opioid receptors. Instead of controlling withdrawal and cravings, it treats opioid use disorder by preventing any opioid drug from producing rewarding effects such as euphoria. Its use for ongoing opioid use disorder treatment has been somewhat limited because of poor adherence and tolerability by patients. However, in 2010, an injectable, long-acting form of naltrexone (Vivitrol), originally approved for treating alcohol use disorder, was FDA-approved for treating opioid use disorder. Because its effects last for weeks, Vivitrol is a good option for patients who do not have ready access to health care or who struggle with taking their medications regularly.

Each medication works differently, therefore a treatment provider should decide on the optimal medication in consultation with the individual patient and should consider the patient’s unique history and circumstances.

Methadone

Methadone is the medication with the longest history of use for opioid use disorder treatment, having been used since 1947. A large number of studies (some of which are summarized in the graph below) support methadone’s effectiveness at reducing opioid use. A comprehensive Cochrane review in 2009 compared methadone-based treatment (methadone plus psychosocial treatment) to placebo with psychosocial treatment and found that methadone treatment was effective in reducing opioid use, opioid use-associated transmission of infectious disease, and crime. Patients on methadone had 33% fewer opioid-positive drug tests and were 4.44 times more likely to stay in treatment compared to controls. Methadone treatment significantly improves outcomes, even when provided in the absence of regular counseling services ^{, ,} ; long-term (beyond 6 months) outcomes are better in groups receiving methadone, regardless of the frequency of counseling received.

Buprenorphine

Buprenorphine, which was first approved in 2002, is currently available in two prescription forms: alone (Probuphine, Sublocade, and Bunavail) and in combination with the opioid receptor antagonist naloxone (Suboxone, Zubsolv). Both formulations of buprenorphine are effective for the treatment of opioid use disorders, although some studies have shown high relapse rates among patients tapered off buprenorphine compared to patients maintained on the drug for a longer period.

A Swedish study compared patients maintained on 16 mg of buprenorphine daily to a control group that received buprenorphine for detoxification (6 days) followed by placebo. ⁵¹ All patients received psychosocial supports. In this study, the treatment failure rate for placebo was 100% versus 25% for buprenorphine. More than two opioid-positive urine tests within 3 months resulted in cessation of treatment, so treatment retention was closely related to relapse. Of patients not retained in treatment, there was a 20% mortality rate.

Meta-analysis determined that patients on doses of buprenorphine of 16 mg per day or more were 1.82 times more likely to stay in treatment than placebo-treated patients and that buprenorphine decreased the number of opioid-positive drug tests by 14.2% (the standardized mean difference was −1.17). ^{, 65}

To be effective, buprenorphine must be given at a sufficiently high dose (generally, 16 mg per day or more). Some treatment providers wary of using opioids have prescribed lower doses for short treatment durations, leading to failure of buprenorphine treatment and the mistaken conclusion that the medication is ineffective. ^,