Abundant evidence shows that methadone, buprenorphine, and naltrexone all reduce opioid use and opioid use disorder-related symptoms, and they reduce the risk of infectious disease transmission as well as criminal behavior associated with illicit substance use. These medications also increase the likelihood that a person will remain in treatment, which itself is associated with lower risk of overdose mortality, reduced risk of HIV and HCV transmission, reduced criminal justice involvement, and greater likelihood of employment.
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 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 percent 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 was first approved in 2002 and is effective for the treatment of opioid use disorders, is effective, has some studies showing high relapse rates among patients tapered off of buprenorphine compared to patients maintained on the drug for a longer period of time.
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. All patients received psychosocial supports. In this study, the treatment failure rate for placebo was 100 percent vs. 25 percent 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 percent mortality rate.
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.
Notably, flexible dose regimens of buprenorphine and doses of buprenorphine of 6 mg or below are less effective than methadone at keeping patients in treatment, highlighting the need for delivery of evidence-based dosing regimens of these medications.
Naltrexone was initially approved for the treatment of opioid use disorder in a daily pill form. It does not produce tolerance or withdrawal. Poor treatment adherence has primarily limited the real-world effectiveness of this formulation. As a result, there is insufficient evidence that oral naltrexone is an effective treatment for opioid use disorder. A newer form of extended-release injectable naltrexone is administered once monthly, which removes the need for daily dosing. While this formulation is the newest form of medication for opioid use disorder, evidence to date suggests that it is effective in certain populations in some circumstances. While the oral formulation will also block opioid receptors, only the long-acting injectable formulation is FDA approved as MAT.
To reduce the risk of withdrawal symptoms caused by OUD, patients should wait at least 7 days after their last use of short-acting opioids and 10 to 14 days for long-acting opioids, before starting naltrexone.
Patients on naltrexone, who discontinue use or relapse after a period of abstinence, may have a reduced tolerance to opioids. Therefore, taking the same, or even lower doses of opioids used in the past can cause life-threatening consequences.
*Data and Reference Information Obtained from NIDA.gov and SAMHSA.gov