Of note, our results should be interpreted in conjunction with known differences in medication adherence. The true practical effectiveness of antagonist therapies may be hindered by lower medication adherence associated with naltrexone compared with agonist treatments in the OUD population. For instance, substantially greater medication adherence has been observed for buprenorphine treatment (median filled prescriptions of 19 months) compared with both extended-release (9 months) and oral (5 months) naltrexone,29 with patients with OUD found to show similar adherence to methadone and buprenorphine.30 As our study evaluates ORs that describe protective outcomes associated with medication at a given point in time, the protective outcomes observed in association with buprenorphine and methadone treatment days are likely to be amplified by their higher adherence rates compared with naltrexone. However, our analyses rely on the implicit assumption that risks associated with medication or lack of medication are constant over time. More investigation is needed to evaluate how these risks might vary before, during, and after OUD treatment, in addition to investigating the comparative effectiveness of buprenorphine, methadone, and naltrexone in suppressing alcohol use in patients with OUD.
