Comparative Effectiveness of Naltrexone Formulations in Alcohol Use Disorder: An Updated Meta-Analysis.

Abstract

Purpose: We aimed to synthesize and provide an updated meta-analysis of the current data on extended-release naltrexone (XR-NTX) and oral naltrexone (NTX) for alcohol use disorder (AUD).

Methods: A comprehensive database search was conducted and updated on October 1, 2025. This meta-analysis encompassed randomized controlled trials (RCTs) and observational studies that compared XR-NTX and oral NTX in adults with AUD. Included studies reported outcomes on treatment persistence and healthcare utilization, specifically ED visits and inpatient hospitalizations during follow-up. Odds ratios (ORs) were computed using the Mantel-Haenszel random-effects model.

Results: Out of 101 studies screened, seven studies (N = 42,268; n = 2,103 for XR-NTX, n = 40,165 for NTX) met the inclusion criteria for the meta-analysis. Overall, treatment persistence was significantly higher with XR-NTX compared with oral NTX (OR = 1.94 [95% CI, 1.22-3.10]), with benefits observed at both three months (pooled OR = 2.24 [95% CI, 1.14-4.41], p = 0.019) and six months (OR = 1.59 [95% CI, 1.04-2.43], p = 0.032). No significant differences were observed in healthcare utilization, including all-cause ED visits (OR = 1.33 [95% CI, 0.93-1.90]) or all-cause inpatient admissions (OR = 0.84 [95% CI, 0.49-1.43]).

Conclusion: This meta-analysis suggests higher treatment persistence among patients with AUD receiving XR-NTX versus oral NTX, underscoring formulation as a key factor in persistence and retention. However, alcohol-related healthcare utilization metrics, including ED visits and hospitalizations, showed no significant between-group differences. Further pragmatic trials accounting for patient preferences, sex-specific outcomes, and barriers to care accessibility are needed.