REVIEW OF: Lei F et al, J Addict Med 2024;18(3):319–326

STUDY TYPE: Retrospective cohort study

Buprenorphine has long been a first-line treatment for opioid use disorder (OUD), but research is limited on optimal dosing strategies early in treatment. Moreover, most of the data supporting its use came from a time when heroin was the dominant opioid—not fentanyl, which is much more potent and now ubiquitous. Earlier studies suggested that maintenance doses of 16 mg/day or higher were optimal for reducing opioid use and improving treatment retention (Mattick RP et al, Cochrane Database System Rev 2014(2):CD002207). But does that guidance hold up early in treatment, particularly with fentanyl now driving overdose deaths?

To address this concern, researchers used data from the Kentucky Prescription Drug Monitoring Program to examine how different buprenorphine doses in the first 30 days of treatment influenced mortality over the following year. Patients were grouped by average daily dose into three categories: low (≤8 mg/day), medium (>8–16 mg/day), and high (>16 mg/day). The study included 49,857 adults starting buprenorphine treatment, with 21.1% in the low-dose group, 49.2% in the medium-dose group, and 29.7% in the high-dose group. Over one year of follow-up, there were 227 opioid-involved overdose deaths (33% of all deaths) and 459 deaths from other causes (67%).

The results revealed a compelling dose-response difference. Compared to the low-dose group, patients in the medium-dose group had a 55% lower risk of opioid-involved overdose death. Those in the high-dose group saw a 64% reduction. Deaths from other causes were also lower (by 22% in the medium-dose group and 38% in the high-dose group). Similar patterns emerged for all-cause mortality, which fell by 37% and 50% respectively.

The authors note several limitations. Because the study used data from a single state, the findings may not apply to other regions. Prescriptions filled out of state and records of long-acting injectable buprenorphine were not included. Additionally, demographic information was incomplete, limiting the ability to control for confounding factors. Still, the consistent dose-response across all mortality outcomes strengthens the case that higher buprenorphine doses in the first month of treatment could substantially improve survival.

CARLAT TAKE
This study reinforces the importance of prescribing higher buprenorphine doses early in treatment—particularly in the fentanyl era. Higher doses were clearly linked to lower mortality from both overdose and other causes. The takeaway: Avoid underdosing in the critical first month. Doing so may leave patients unprotected and at higher risk of death.