June 4, 2024

About 63% of people with active opioid use disorder (OUD) were able to start injectable extended-release opioid antagonist treatment within a week using a rapid initiation procedure. The standard initiation process takes 10 to 15 days, and at the end, only 36% of people with active OUD successfully transitioned to the extended-release opioid antagonist. Although the rapid procedure was as effective as the standard process at transitioning people to the extended-release opioid antagonist, it was associated with a higher number of safety events and serious adverse events. 

Use of an opioid antagonist requires that the individual with active OUD gradually withdraw from opioids to avoid precipitated withdrawal. Alkermes, Inc., the maker of the injectable extended-release opioid antagonist drug recommends a seven-to-ten-day opioid-free period before starting the drug. 

The standard protocol starts with a three-to-five-day taper. In total, the standard protocol lasts from 10 to 15 days before it can be administered. 

The rapid protocol includes one day of a partial agonist opioid treatment, followed by one opioid-free day, and ascending low doses of an opioid antagonist and adjunctive non-opioid medications to treat symptoms of opioid withdrawal as measured using the Clinical Opiate Withdrawal Scale (COWS) scores, which range from 0 to 48 (highest severity). The first daily dose of the opioid antagonist was given if the COWS score was lower than 6. A second dose was given the same day four hours later, unless the COWS score increased by three or more points after the initial dose. The protocol lasts from five to seven days. 

These findings were reported in a study by Matisyahu Shulman, M.D.; Miranda G. Greiner, M.D., MPH; Hiwot M. Tafessu, MS; and colleagues. They conducted a six-site stepped wedge cluster randomized clinical trial that included 415 individuals with active opioid use disorder (OUD) admitted to an inpatient addiction treatment plan. Over 70 weeks, five of the sites, one at a time, were randomly assigned to switch from their standard procedure to the rapid procedure; and one site, acting as a control, continuously used its standard procedure. The opioid antagonist was offered only to those individuals who expressed interest. 

The individuals served by the sites received the initiation procedure for the opioid antagonist in use by their site at the time of admission. After the inpatient stay, all participants were referred to outpatient addiction treatment and followed for up to eight weeks. The second and third doses of the opioid antagonist were offered at weeks 4 and 8 after the first dose. 

The full text was published May 8, 2024, by JAMA Network Open.