Naltrexone vs Buprenorphine: No Significant Difference in Overdose Risk

When evaluating the comparative effectiveness of naltrexone vs buprenorphine, extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are similarly effective for reducing overdose risk. However, XR-NTX had higher discontinuation rates than SL-BUP. These study results were recently published in Addiction.

Both XR-NTX and SL-BUP are approved for the treatment of opioid use disorder (OUD). Although randomized clinical trials have compared naltrexone vs buprenorphine, the comparative effectiveness of XR-NTX and SL-BUP have not been as robustly evaluated in real-world, usual care settings.

To this aim, researchers conducted a cohort study using Medicaid claims data from 2016 to 2019. The primary outcomes of interest were early treatment discontinuation (before 6 months) and overdose risk among Medicaid patients with OUD in New Jersey and California. Adults aged 18 to 64 years initiating XR-NTX or SL-BUP for OUD treatment without prior medication-assisted treatment use in the past 90 days were included in the study.

A total of 11,641 patients with OUD were included in the analysis. Overall, individuals had a median (interquartile range [IQR]) age of 34 (29-45) years, 56% were men, and 70% were non-Hispanic White. Of the 11,641 patients, 1755 initiated XR-NTX and 9886 initiated SL-BUP. Patients on XR-NTX generally had a higher prevalence of various health conditions, higher healthcare utilization, and greater medication use – especially antidepressants and antipsychotics – relative to those receiving SL-BUP. Conversely, disability and chronic pain were more prevalent among SL-BUP initiators.

For the composite outcome of both medication discontinuation and overdose mortality, 58% of patients experienced an event within 6 months of treatment initiation. By week 26, the adjusted risk for discontinuation after XR-NTX initiation was 76% (95% CI, 74%-78%) compared with 62% after SL-BUP initiation (95% CI, 61%-63%), corresponding to a 14% higher discontinuation rate for XR-NTX over SL-BUP.

For the composite outcome of overdose or death, the crude risk by the end of follow-up was 5.1% (95% CI, 4.1%-6.3%) for XR-NTX and 3.1% (95% CI, 2.7%-3.4%) for SL-BUP. However, after adjustment, the risks were more comparable, 3.9% (95% CI, 3.0%-4.8%) for XR-NTX and 3.3% (95% CI, 2.9%-3.7%) for SL-BUP, with an adjusted risk difference of 0.5 percentage points.

No significant differences were observed in the effect of medication on discontinuation when stratified by alcohol use disorder (AUD) or chronic pain, and the findings remained consistent across sensitivity analyses. The largest risk difference for overdose was 1.2 percentage points (95% CI, -0.5 to 3.0).

Study authors concluded, “Among Medicaid patients in California and New Jersey medication retention was longer on SL-BUP than XR-NTX, although the risk of overdose was similar.”

Study limitations include potential residual confounding and measurement error. Additionally, the results may not be generalizable beyond the study cohort.

Disclosure: One study author reported affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor