REVIEW OF: Hassman H et al, Am J Drug Alcohol Abuse 2023;49(1):43–52

STUDY TYPE: Open-label, prospective cohort study

The long-acting injectable form of buprenorphine, Sublocade (XR-BUP), is a promising alternative to sublingual formulations for the treatment of opioid use disorder (OUD), especially for patients who have challenges with adherence. However, the manufacturer recommends that patients be stabilized on a dose of sublingual buprenorphine for at least seven days before the first XR-BUP injection, a period that could lead to delays in treatment or dropping out of care. But is this waiting period necessary?

In this open-label study, researchers assessed the safety and tolerability of starting XR-BUP after a single 4 mg dose of sublingual buprenorphine. A total of 26 participants with moderate or severe OUD were recruited for the study. They stopped using opioids and were given a single 4 mg dose of sublingual buprenorphine once their COWS score was 8 or above. After one hour, as long as there was no precipitated withdrawal (defined as a ≥6-point increase in COWS score), researchers administered a 300 mg dose of XR-BUP. Participants were subsequently monitored as inpatients for 48 hours. Any residual withdrawal symptoms were treated with a small sublingual dose of buprenorphine or with symptom-specific medications (clonidine, ondansetron, NSAID, loperamide, etc).

Of the 26 participants who received the 4 mg sublingual dose, 24 received the XR-BUP injection. Overall, mean COWS score dropped from 14.6 ± 4.1 at the time of injection, to 6.9 ± 4.1 at six hours, to 4.2 ± 3.2 at 24 hours. Most participants (62.5%, n=15) experienced their most severe withdrawal symptoms prior to XR-BUP administration, though a minority (37.5%, n=9) did experience their most severe symptoms after getting XR-BUP. The patients whose symptoms were most severe after receiving XR-BUP experienced a slower overall reduction in COWS scores than those whose symptoms improved after receiving XR-BUP. 

In total, 15 patients received sublingual buprenorphine or symptomatic treatment during the 48-hour observation period. Two patients met criteria for precipitated withdrawal after receiving XR-BUP; one had COWS scores increase from 15 to 22 over one hour and another had COWS scores increase from 3 to 11 over two hours. But even for these participants, COWS scores steadily declined over time. All participants had no active withdrawal or only mild symptoms by 12 hours after injection. There were no serious adverse events, and most tolerated the medication well. One month after the administration of the XR-BUP injection, 30% of the participants had opioid-negative urine samples.

Carlat Take 

This is a small open-label trial, so the results should be interpreted with a grain of salt, and the 48-hour inpatient observation period makes it impractical to duplicate this protocol in a clinical setting. However, the study does show that the full seven-day waiting period is probably unnecessary, affording providers more flexibility in formulating individualized treatment approaches.