Naltrexone

Naltrexone is a medication for opioid use disorder (OUD) that is administered as a once monthly long-acting injection. It is used less often than medications like methadone and buprenorphine, but can effectively reduce illicit opioid use and the risk of death from an opioid overdose.

Naltrexone — Evidence Rating: Moderate Quality

Naltrexone is one of three FDA-approved evidence-based medications for opioid use disorder. Data supporting naltrexone comes from randomized clinical trials and observational studies. Trials have generally found that once naltrexone is successfully initiated, it is effective for reducing opioid use. However, naltrexone is complicated to initiate for many individuals because of its requirement for a longer period of medically supervised withdrawal or opioid abstinence. Both randomized trials and observational studies find that naltrexone is less effective than buprenorphine or methadone for reducing opioid use and the risk of overdose death among patients who have not stopped using opioids. Its effectiveness is more comparable to other medication options when compared after the patient has stopped using opioids. Naltrexone is more effective than not taking any medications for opioid use disorder.

Evidence-based Scale

Naltrexone is an FDA-approved medication for opioid use disorder (OUD) that is administered as a once monthly long-acting injection (also referred to as extended- release or “XR” naltrexone). Although there is also a pill form of naltrexone, this formulation is approved only for the treatment of alcohol use disorder. The use of oral naltrexone for OUD is considered “off-label” and not approved by the FDA. Naltrexone works by blocking the effects of opioids in the brain and body. This makes it fundamentally different from other medications for opioid use disorder, such as buprenorphine and methadone, which maintain a steady level of opioid effects. Because of these blocking properties, naltrexone can cause uncomfortable withdrawal symptoms if given to someone while other opioids are still in the body. As a result, naltrexone is typically given to individuals who have already abstained from opioids for a period of time or who complete a period of medically supervised withdrawal referred to as detoxification. Naltrexone then helps to prevent future opioid cravings and blocks the effects of any opioids that are taken. When compared to buprenorphine and methadone, naltrexone has been shown to be less effective at reducing opioid use and opioid-related death – mostly owing to the substantial induction hurdle that must be overcome to start naltrexone. Thus, naltrexone is less frequently used in real-world practice, but when it is successfully initiated, it has similar effectiveness to buprenorphine.