Background Opioid dependence is a severe and often lifelong disorder with a high risk of overdose and premature death, as well as severe psychosocial difficulties. Sustained‐release naltrexone is a treatment option that works by blocking the euphoric and overdose effects of opioids. When injected intramuscularly, naltrexone provides blockade for one month, while the blocking effects with implants can last for up to six months.

Objective To assess the benefits and harms of sustained‐release naltrexone for the treatment of opioid dependence.

Search methods For this update, we searched the following databases from 2007 up to 20 December 2023: the Cochrane Drugs and Alcohol Specialised Register of Trials, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, ISI Web of Science, LILACS, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform.

We manually searched the reference lists of identified studies, published reviews and relevant websites.

Selection criteria Randomised controlled trials comparing the effects of injectable or implantable naltrexone with other treatment, no treatment or placebo in adults with opioid dependence.

Data collection and analysis Primary outcomes were illicit opioid use, retention in treatment, treatment acceptability and adverse events. Secondary outcomes were opioid craving, recreational use of substances other than opioids, mental health, quality of life and criminal activity.

We assessed the risk of bias using the Cochrane risk of bias tool (RoB 1). We combined the results of individual trials through meta‐analysis where possible using a random‐effects model. Two review authors independently assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results We identified 22 studies (3416 participants) that met our inclusion criteria. Three studies compared sustained‐release naltrexone with opioid agonist treatment, five with oral naltrexone, six with placebo, nine with treatment as usual and one with psychosocial intervention.