High-dose buprenorphine treatment showed mixed outcomes among patients with opioid use disorder in the setting of fentanyl use. Research suggested benefits for retention and reduced health care utilization, but evidence remained limited on whether higher initiation doses lowered the risk of precipitated withdrawal.

Precipitated Withdrawal (PW) occurred in 1% to 16% of patients initiating buprenorphine with fentanyl exposure. In a study of 1,200 patients in 28 emergency departments, PW developed in nine patients, all of whom had fentanyl detected. A separate analysis of 226 hospitalized patients reported PW in 16% of fentanyl users compared with 6% of nonusers. Another review of 492 patients in California emergency departments showed PW in 5% of fentanyl users compared with 1% of nonusers.

Evidence did not show that higher starting doses reduced PW. No randomized clinical trials have directly compared high- and standard-dose initiation strategies. In one hospital-based study, patients who received 8 mg or more were not less likely to experience PW than those starting with lower doses. 

Data on treatment retention suggested an advantage with higher doses. Among 6,499 patients in Rhode Island, 59% of those prescribed 16 mg discontinued treatment within 180 days compared with 53% prescribed 24 mg. A national analysis of more than 620,000 prescription claims also showed higher retention at all time points for patients receiving 24 mg or more. 

Health care utilization outcomes similarly favored higher dosing. In a study of 35,451 patients, those prescribed more than 16 mg had longer time before requiring emergency or inpatient care compared with those prescribed 16 mg or less.

Limitations included the observational design of all studies, which introduced risks of confounding, selection bias, and immortal time bias. The relatively small number of PW cases also restricted the ability to fully assess differences between fentanyl and non-fentanyl users. Researchers noted that randomized clinical trials are needed to provide stronger evidence for clinical decision-making in the fentanyl era.

The authors reported no conflicts of interest.

Source: JAMA Network Open