Journal Article Annotations
2023, 4th Quarter


Annotations by Julian J. Raffoul, MD, PhD
January, 2024

  1. Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder

PUBLICATION #1 — Addiction

Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder
Mark K Greenwald, Katharina L Wiest, Barbara R Haight, Celine M Laffont, Yue Zhao


The finding:
The current recommended dose of buprenorphine extended-release (BUP-XR) for opioid use disorder (OUD) following open-label induction and dose stabilization with sublingual buprenorphine/naloxone is 300-mg monthly for the first two months followed by a maintenance dose of 100-mg monthly. In this secondary analysis of a randomized, double-blind, placebo-controlled study that enrolled treatment-seeking adults who met the DSM-5 criteria for moderate or severe OUD at screening, the utilization of a higher 300-mg maintenance dose of BUP-XR for the treatment of OUD in patients who inject opioids resulted in improved treatment retention and abstinence from opioids over the standard 100-mg maintenance dose. Furthermore, exposure-response analyses confirmed that patients who inject opioids likely require higher buprenorphine plasma concentrations compared to opioid non-injecting patients to achieve and maintain abstinence. Interestingly, the standard 100-mg maintenance dose and experimental 300-mg maintenance doses were equally effective in patients who do not inject opioids and both maintenance doses had comparable safety profiles.

Strength and weaknesses:
This study demonstrated a clear benefit for utilizing the 300-mg maintenance dose for patients who inject opioids. This is an important finding as opioid-injecting patients are a high-risk and difficult-to-treat patient population and optimal dosing for this group would facilitate harm-reduction by improving treatment retention and abstinence promotion. A limitation of this study was that it did not compare the BUP-XR 300-mg versus 100-mg during the maintenance dose period in the randomized intent-to-treat population. As a result, the treatment comparison could have been subject to the bias introduced by participants discontinuation prior to receiving the maintenance dose. Unmeasured confounders may have also influenced the efficacy of comparison results.

Despite the availability of effective treatments for OUD such as buprenorphine, methadone, and naltrexone, opioid use remains at epidemic levels in the US. Factors such as opioid use duration, frequency of use, use via injection, and inadequate therapeutic doses of treatments, particularly buprenorphine treatments, are all associated with increased likelihood of return to use. C-L psychiatrists need to be familiar with strategies to improve OUD treatment and retention in these highly vulnerable patient populations. Patients who inject opioids and prescribed a maintenance dose of 300-mg of BUP-XR maintained abstinence and remained in treatment longer than those prescribed the 100-mg maintenance dose. Recommending higher doses of buprenorphine for patients with OUD, particularly patients who inject opioids and/or use synthetic opioids such as fentanyl, may need higher doses of buprenorphine for effective treatment.