MAY 23, 2024
Initiating opioid use disorder (OUD) therapy with extended-release, injectable naltrexone (XR-naltrexone) within five to seven days of a patient’s seeking treatment is more effective than the standard treatment method of starting within 10 to 15 days, but requires closer medical supervision, according to results from a clinical trial supported by the National Institutes of Health’s National Institute on Drug Abuse (NIDA (JAMA Netw Open 2024;7[5]:e249744).
“Time has been an
Initiating opioid use disorder (OUD) therapy with extended-release, injectable naltrexone (XR-naltrexone) within five to seven days of a patient’s seeking treatment is more effective than the standard treatment method of starting within 10 to 15 days, but requires closer medical supervision, according to results from a clinical trial supported by the National Institutes of Health’s National Institute on Drug Abuse (NIDA (JAMA Netw Open 2024;7[5]:e249744).
“Time has been an important barrier that we’ve seen hinder the use of extended-release naltrexone for opioid use disorder in the past, both among individuals and treatment providers,” said Matisyahu Shulman, MD, a clinician researcher at New York State Psychiatric Institute and Columbia University Irving Medical Center, New York City, and lead author of the study, in a press release. “We hope that these findings can help encourage more treatment settings to offer extended-release naltrexone as a safe and effective option for patients, to help prevent overdose and support recovery.”
Starting treatment with XR-naltrexone has traditionally required patients to go through a seven- to 10-day opioid-free period, to avoid experiencing painful withdrawal symptoms caused when naltrexone abruptly stops the effects of opioids in the brain. During this waiting period, patients are at high risk of returning to opioid use or discontinuing treatment, “a significant barrier to implementation of XR-naltrexone,” according to the NIH in a press release.
Researchers tested the effectiveness of a more rapid procedure to start people with OUD on XR-naltrexone. Between March 2021 and September 2022, the study enrolled and followed 415 patients with OUD who were admitted at six community-based inpatient addiction facilities across the United States and who chose treatment with XR-naltrexone. Every 14 weeks, the sites were randomized to either provide the standard XR-naltrexone or the more rapid procedure.
In the study, standard XR-naltrexone prescribing included a three- to five-day treatment period with buprenorphine to ease withdrawal symptoms, followed by a seven- to 10-day opioid-free period. The rapid procedure consisted of one day of buprenorphine (up to 10 mg), a 24-hour opioid-free period and a gradual increase in low-dose oral naltrexone for three to four days prior to getting an injection of XR-naltrexone. Doctors also used medications such as clonazepam and clonidine throughout the process to manage withdrawal symptoms.
Patients on the rapid five- to seven-day treatment procedure were significantly more likely to receive a first injection of XR-naltrexone compared with those on the standard seven- to 15-day treatment procedure (62.7% vs. 35.8%). Withdrawal severity was generally low and comparable across the two groups. Targeted safety events and serious adverse events (e.g., a fall or overdose) were infrequent overall but occurred more with the rapid procedure (5.3% and 6.7%) than on the standard procedure (2.1% and 1.6%), and the rapid procedure required more staff attention.
The authors note that future studies should explore sustainability, feasibility and health economic aspects of this more rapid treatment protocol.
Based on a press release from the NIH.
