Death by drug overdose is the number one cause of death in Americans 50 years of age and younger.1 In 2016, there were 63,632 drug overdose deaths in the United States2 Opioids were involved in 42,249 of these deaths, which represents 66.4% of all drug overdose deaths.2 From 2015 to 2016, the age-adjusted rate of overdose deaths increased significantly by 21.5% from 16.3 per 100,000 to 19.8 per 100,000.2 This means that every day, more than 115 people in the United States die after overdosing on opioids. The misuse of and addiction to opioids—including prescription pain relievers, heroin, and synthetic opioids such as fentanyl—is a serious national crisis that affects public health as well as social and economic welfare.
The gold standard treatment is medication-assisted treatment (MAT)—the use of FDA-approved medications, in combination with counseling and behavioral therapies, to provide a “whole-patient” approach.3 When it comes to MAT options for opioid use disorder (OUD), there are 3 medications, each with its own caveats.
Methadone is an opioid mu-receptor full agonist that prevents withdrawal but does not block other narcotics. It requires daily dosing as a liquid formulation that is dispensed only in regulated clinics.
Buprenorphine is a mu-receptor high affinity partial agonist/antagonist that blocks the majority of other narcotics while reducing withdrawal risk. It requires daily dosing as either a dissolving tablet or cheek film. Recently it has also become available as a 6-month implant as well as a 1-month subcutaneous injection. Buprenorphine is also available as a combined medication with naloxone; naloxone is an opioid antagonist.
Naltrexone is a mu-receptor antagonist that blocks the effects of most narcotics. It does not lead to dependence, and is administered daily as a pill or monthly as a deep IM injection of its extended-release formulation.
The first 2 medications are tightly regulated options that are not available in many areas of the United States. Naltrexone, when provided as a daily pill, has adherence issues. As with any illness, lack of adherence to treatment is problematic; in the case of patients with OUD, this includes a high risk of overdose and death.
The use of injectable extended-release naltrexone (XR-NTX) may be a way to address nonadherence and thus prevent relapse. One of the challenges limiting naltrexone’s applicability has been the length of time required for an “opioid washout” of the mu receptors prior to administering naltrexone, which is a mu blocker. The washout can take as long as 7 to 10 days. This interval is not feasible for patients receiving inpatient treatment, and patients receiving treatment as outpatients are vulnerable to relapse during this time. Recently, there have been several attempts to shorten this gap through various experimental protocols based on incremental doses of NTX to facilitate withdrawal while managing symptoms.
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