For adolescents and adults with opioid dependence (mostly male adults, all in high‐income countries), sustained‐release naltrexone—administered via injections or implants for two to six months—reduces illicit opioid use, based on urine test results, when compared with usual care (including opioid agonist treatment, non‐pharmacological approaches, or both; 457 vs 639 per 1000 people; all results on average; high‐certainty evidence). Sustained‐release naltrexone treatment probably also results in fewer serious adverse events, although their nature was not described (70 vs 119 per 1000 people; moderate‐certainty evidence). Although sustained‐release naltrexone may be less acceptable to patients, with fewer people starting treatment (790 vs 1000 per 1000 people), treatment retention may be similar (low‐certainty evidence).

Effects on other outcomes are mixed or unclear, and the certainty of evidence was not assessed; non‐serious adverse events may be more common with sustained‐release naltrexone, while depression may be less common. There may be little to no difference between groups in self‐reported illicit opioid use, number of days of self‐reported use, overall opioid‐negative drug test results, overdoses, deaths, use of other substances (alcohol, cannabis, amphetamines, or cocaine), psychiatric disorders, quality of life, or criminal activity.

No studies reported on opioid craving...