A scoping review of naltrexone treatment for opioid use disorder: Clinical hurdles and successes.

Objective

To understand the use of naltrexone for the treatment of Opioid Use Disorder (OUD). We reviewed different formulations' effectiveness, clinical hurdles, potential safety concerns, and explored how specific sub-populations fared on naltrexone.

Methods

The review followed PRISMA-ScR guidelines and was registered in Open Science Framework (hs3g6). We included searches of the MEDLINE, Embase, and Cochrane Central Databases, using predetermined eligibility criteria, including English language studies from 1984 to 2026 investigating naltrexone treatment for OUD. Extracted data included: publication year, country, study type, naltrexone formulation, treatment setting, comparator, key findings, and limitations.

Results

Our search yielded 3219 references and 181 were ultimately included. Most studies were randomized controlled studies and secondary analyses (58%), involved injectable formulations (61.3%), and were conducted in the United States (57.5%). We identified patient characteristics and settings associated with better outcomes, including inpatient setting, highly motivated patients, and patients with prescription opioid use history, among others. Naltrexone induction remains a clinical hurdle and treatment cessation carries risk of subsequent overdose.

Conclusions

Naltrexone is the least utilized medication for OUD because of induction-related clinical hurdles despite its comparable post-stabilization effectiveness with other medications for OUD. Further research is warranted on how to expand its clinical use.