Abstract
PURPOSE: This systematic review and meta-analysis aimed to compare extended-release naltrexone (XR-NTX) and oral naltrexone (NTX) for treating substance use disorders (SUDs). METHODS: A comprehensive search of multiple databases (MEDLINE, Embase, Cochrane, APA PsycInfo, and Scopus) was conducted on October 1, 2024, with no date or language restrictions. Inclusion criteria were adults with SUDs, interventions with XR-NTX, comparisons with oral NTX, and outcomes on treatment persistence, hospitalizations, and emergency department (ED) visits. Randomized controlled trials (RCTs) and observational studies were included. Odds ratios were calculated using the Mantel-Haenszel random-effects model. RESULTS: Of the 1116 studies screened, 27 were selected for full-text review, 15 met the inclusion criteria (3 open-label RCTs [n = 340] and 12 retrospective studies [n = 18,695]) focusing on alcohol use disorder (AUD) and opioid use disorder (OUD), and 7 were included in the meta-analysis. We found no other SUD where the two interventions were compared. Treatment persistence was significantly higher with XR-NTX compared to oral NTX at both 3 months (OR 1.43 [95 % CI: 1.04-1.96], p = 0.03) and 6 months (OR 1.96 [95 % CI: 1.37-2.81], p = 0.0002). No significant differences were observed in healthcare utilization, including inpatient admissions (OR 0.69 [95 % CI: 0.30-1.61], p = 0.39) or ED visits (OR 1.17 [95 % CI: 0.61-2.26], p = 0.63). CONCLUSIONS: Patients with AUD and OUD receiving XR-NTX stay in treatment longer than those receiving oral NTX. However, hospitalization and ED visit rates did not differ. Findings are limited due to a small number of RCTs.