Fentanyl is 50-times more potent than heroin, drastically raising the rate of overdose deaths
In the fentanyl era, going above the standard buprenorphine dose may keep patients in treatment without added danger
STUDY: Chambers L et al, International Journal of Population Data Science 2026
STUDY TYPE: Retrospective cohort study
FUNDING: Independent
Background
We learned how to dose buprenorphine (eg, Suboxone) before fentanyl, and have little research to guide us in the fentanyl era. Fentanyl is 50-times more potent, leading to more withdrawal problems and greater overdose risk. Anecdotally, some recommend dosing buprenorphine above the standard 16 mg/day ceiling. This study tests that idea with real-world data.
The Study
- 8,676 Rhode Island residents starting buprenorphine for opioid use disorder between October 2016 and September 2022, linked across five state databases covering prescribing, emergency medical services, medical examiners, vital records, and behavioral health treatment.
- Compared overdose risk on days with versus without active buprenorphine treatment over the following year.
- Compared time to treatment discontinuation over 180 days for patients started at 16 mg versus 24 mg.
Results
Starting on the 16 mg dose was linked to a 20% higher discontinuation rate compared to 24 mg (adjusted hazard ratio 1.20, 95% CI 1.06–1.37).
Overdose risk was 61% lower on days patients were taking buprenorphine compared to days they weren’t (adjusted risk ratio 0.39, 95% CI 0.31–0.49). Doses didn’t differ between overdose days and non-overdose days, so higher doses weren’t tied to more overdoses.
Limitations
Observational data, so doesn’t control for confounders. Though large, the data comes from only one state in the US.
Practice Implications
- Buprenorphine keeps protecting against overdose even in the fentanyl era, and that protection depends on patients staying on it.
- If a patient on 16 mg is still struggling with cravings or early dropout, this data supports titrating up toward 24 mg rather than holding the line at the old ceiling.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
2 comments
Stephen Wyatt DO
August 8, 2026 at 10:03 am
Buprenorphine has a significantly higher affinity to the opioid receptor than fentanyl. Consequently, there is a clear understanding, and strong real world evidence that buprenorphine would be protective from overdose of fentanyl. Increasing. the dose would only increase the protective potential.
Using higher doses of buprenorphine to more effectively engage the patient that has been using fentanyl and reduce their cravings is also well established. However, as far back as Walter Ling’s study at UCLA and 1998, there is good evidence that using higher doses though protective and effective in reducing relapse to opioid use, there is no evidence or reason to believe that a patient needs to be maintained on these higher doses weeks to months later.
Chris Aiken, MD
August 9, 2026 at 8:07 am
Thank you Steve always appreciate your wisdom and the good work you’re doing in this field