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Updated: Mar 14, 2026

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training
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Comparative Effectiveness of Naltrexone Formulations in Alcohol Use Disorder: An Updated Meta-Analysis.

Nicolas A Nunez1, Hossam M Ali2, Leslie Hassett3

  • 1Nunez, MD, MS, Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.

Psychopharmacology Bulletin
|March 13, 2026
PubMed
Summary

Extended-release naltrexone (XR-NTX) significantly improves treatment persistence for alcohol use disorder (AUD) compared to oral naltrexone (NTX). However, both formulations showed similar healthcare utilization rates, including emergency department visits and hospitalizations.

Keywords:
alcohol use disorderefficacyextended-release injectable naltrexoneformulationsmeta-analysisoral naltrexone

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Area of Science:

  • Pharmacology
  • Addiction Medicine
  • Health Services Research

Background:

  • Alcohol use disorder (AUD) is a chronic relapsing condition requiring effective long-term management.
  • Naltrexone, available in oral and extended-release injectable formulations, is a key medication for AUD treatment.
  • Understanding the comparative effectiveness of different naltrexone formulations on treatment persistence and healthcare utilization is crucial for clinical practice.

Purpose of the Study:

  • To conduct an updated meta-analysis of current data comparing extended-release naltrexone (XR-NTX) and oral naltrexone (NTX) for AUD.
  • To evaluate the impact of XR-NTX versus oral NTX on treatment persistence and healthcare utilization in adults with AUD.

Main Methods:

  • A comprehensive database search was performed, updated October 1, 2025.
  • Included randomized controlled trials and observational studies comparing XR-NTX and oral NTX in adults with AUD.
  • Analyzed outcomes included treatment persistence, emergency department (ED) visits, and inpatient hospitalizations using random-effects meta-analysis.

Main Results:

  • Seven studies (N = 42,268) met inclusion criteria.
  • Treatment persistence was significantly higher with XR-NTX compared to oral NTX (OR = 1.94), with benefits seen at 3 and 6 months.
  • No significant differences were found in all-cause ED visits (OR = 1.33) or inpatient admissions (OR = 0.84) between the two formulations.

Conclusions:

  • Extended-release naltrexone formulation is associated with superior treatment persistence in AUD patients compared to oral naltrexone.
  • Formulation plays a key role in patient persistence and retention in AUD treatment.
  • Further research is needed to explore patient preferences, sex-specific outcomes, and access barriers in pragmatic trials.