Kornør 2025 (Cochrane): long-acting naltrexone for opioid dependence

What they tested

Cochrane reviews pool randomized trials using strict methods. This update searched databases up to 20 December 2023 for trials comparing injected or implanted naltrexone with other treatment, no treatment or placebo in adults with opioid dependence. An injection blocks opioids for one month, and implants can last up to six months.

Of the 22 studies, 3 compared long-acting naltrexone with opioid agonist treatment (medicines such as methadone or buprenorphine that activate opioid receptors), 5 with oral naltrexone, 6 with placebo, 9 with treatment as usual and 1 with a psychosocial treatment. The authors rated how certain each result was using the GRADE approach.

What they found

Compared with treatment as usual, long-acting naltrexone reduced illicit opioid use during treatment (RR 0.72, 95% CI 0.57 to 0.90; high certainty) and probably reduced serious adverse events (RR 0.59; moderate certainty). It may have made little or no difference to staying in treatment and may slightly reduce how acceptable people found the treatment (low certainty).

Compared with opioid agonist treatment, it probably increased illicit opioid use during treatment slightly (RR 1.15; 1 study, 570 participants; moderate certainty) and may slightly increase serious adverse events (RR 1.40; low certainty). Effects on staying in treatment were very uncertain.

Compared with oral naltrexone, it may reduce illicit opioid use (RR 0.65; 1 study, 69 participants; low certainty). Retention looked better (RR 2.40), but the evidence was very uncertain.

Compared with placebo, it may make little to no difference to illicit opioid use (RR 0.83, 95% CI 0.66 to 1.03), treatment acceptability or serious adverse events. The effect on retention (RR 2.10) was very uncertain.

None of the main outcomes were reported for the comparison with psychosocial treatment.

Limits

• Many comparisons rested on one to a few small studies, and the most common weaknesses were risk of performance bias and imprecision.
• There was little long-term data, and the authors said under-represented groups and people using synthetic opioids need more study.

What it means if you're considering naltrexone

For someone with opioid use disorder, this review suggests the naltrexone shot or implant does better than treatment as usual at cutting illicit opioid use, but it doesn't beat methadone or buprenorphine and may do slightly worse. Against daily naltrexone tablets, the long-acting forms looked better, though that evidence is weak.