Rapid Initiation of Naltrexone Exhibits Superiority to Standard Procedure

The rapid procedure (RP) for initiating extended-release (XR) naltrexone for the treatment of opioid use disorder (OUD) demonstrates noninferiority to the standard procedure (SP), according to trial results published in JAMA Network Open. The findings of the study also indicate that the time to initial injection from admission was faster with the RP approach relative to SP.

The SP for initiating XR-naltrexone necessitates that patients with OUD withdraw from opioid treatment to avoid precipitated withdrawal, which can be a significant barrier to initiating treatment. The current prescribing information for XR-naltrexone advises a 7- to 10-day opioid-free period before treatment administration, which typically results in a delay of 10 to 15 days before patients start XR-naltrexone. During this time, patients are vulnerable to potential residual withdrawal symptoms, cravings, and risk of dropping out of treatment. Shortening the time to treatment initiation for patients with OUD could help improve patient outcomes. The current study sought to test the effectiveness of a rapid XR-naltrexone initiation procedure consisting of minimal buprenorphine, use of higher doses of nonopioid medications for opioid withdrawal, and titration of low doses of oral naltrexone compared with usual care in community-based inpatient addiction treatment units.

The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) trial was a stepped-wedge, cluster-randomized design trial conducted over 70 weeks and involved 6 inpatient addiction treatment programs throughout the United States. Investigators offered study participation to individuals who expressed interest in XR-naltrexone treatment. Participants received the initiation procedure (SP or RP) that their program was assigned to at the time of patient admission. The primary study outcome was receipt of the first injection of XR-naltrexone during inpatient status. Secondary outcomes included receipt of second and third XR-naltrexone injections, opioid withdrawal severity, opioid cravings, safety events, and opioid use – measured via self-report and urine drug screen samples.

Across the 6 study sites, a total of 3993 patients were admitted for management of OUD. Among those admitted, 415 (10.4%) opted for XR-naltrexone treatment and agreed to participate in the study, of which 225 participants received the RP and 190 received the SP. Overall, participants had a mean (SD) age of 32.2 (7.69) years, 50.6% were women, and 69.9% were White. At the end of the study, 37.3% of participants did not initiate XR-naltrexone and 56% completed the final week 8 study assessment.

The investigators found that 62.7% of patients who received the RP were successfully administered an XR-naltrexone injection, relative to only 35.8% of participants who received the SP. Patients who received the RP were significantly more likely to receive naltrexone (odds ratio [OR], 3.60; 95% CI, 2.12-6.10) than those who received SP, demonstrating superiority.

Although safety events were rare in both groups, they were more frequent in the RP group than the SP group – particularly for targeted safety events such as falls, acute medical complications, and acute changes in mental status or psychiatric symptoms. During the 8-week follow-up period, 3 participants (1.3%) in the RP group and 6 (3.2%) in the SP group reported nonfatal overdose.

The investigators concluded, “The findings of this trial suggest that a rapid approach to withdrawal management should be considered for patients with OUD attempting to start treatment with XR-naltrexone, but more intensive staffing needs may be a barrier to implementation.”

The generalizability of these findings may be limited, as the study used site-based research teams to assist with the implementation of the RP approach. Additionally, low-dose naltrexone was used in the RP approach but may not be available everywhere.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of author disclosures.

This article originally appeared on Psychiatry Advisor