Research Triangle Center of Excellence in Regulatory Science and Innovation (CERSI)

Abstract There is currently limited information available to indicate whether there is an association between the dose of buprenorphine used for the treatment of opioid use disorder (OUD) and the subsequent risk of mortality. 1,2 Prior studies have suggested that higher buprenorphine doses are associated with improved utilization outcomes such as reduced discontinuation and relapse to opioid use 3,4; however, the specific association between buprenorphine dose and mortality remains underexplored. Furthermore, there is significant heterogeneity in clinical guidelines and the recommendations regarding target dose for transmucosal (TM) buprenorphine and the rate at which it should be reached. It is generally agreed that a stable daily maintenance dose for most patients lies between 4 mg and 24 mg, with 16 mg being a common target. 5,6 Though the FDA-approved labeling states that the clinical benefits of dosing exceeding 24 mg have not been demonstrated, there exists ongoing discussions suggesting that prescribing higher daily dosages (up to 32 mg) could be safe and foster improved patient retention. 7–9. A recently published review concluded that updating the label to recommend dosing up to 32 mg/day and eliminating the 16 mg/day target dose would improve treatment outcomes and save lives.9 However, large population-based studies to elucidate the buprenorphine dose-related impact on clinically relevant outcomes like all-cause and opioid-related overdose mortality in persons with opioid use disorder (OUD) under a causal framework are currently lacking. Similarly, investigation of heterogeneity of treatment effects in special populations (e.g., pregnant persons) is important to consider.