ANN ARBOR, MI — Does rotation of buprenorphine from full μ-opioid receptor agonists improve pain-related outcomes and lessen adverse effects in patients with chronic pain and long-term use of narcotics?
That was the question behind the systematic review of 22 studies that dealt with prespecified outcomes of rotation to buprenorphine. Researchers from the Ann Arbor, MI, VAMC and the University of Michigan reported that low-quality evidence suggested that buprenorphine rotation was associated with reduced pain without causing opioid withdrawal or other serious adverse effects.
“These findings suggest that buprenorphine rotation may be a viable option for mitigating the harms of long-term opioid therapy in individuals with chronic pain who were receiving unsafe opioid analgesic regimens,” the authors wrote in JAMA Network Open, adding that further studies are needed to examine the best way to accomplish buprenorphine rotation.1
The question was deemed important, because chronic pain patients on long-term opioid therapy (LTOT) are at risk of opioid use disorder and other adverse outcomes. The study team noted that, while rotation to buprenorphine might be considered, the outcomes of that type of rotation in this cohort had not been systematically reviewed.
The study focused on the following issues:
- precipitated opioid withdrawal,
- pain intensity,
- pain interference,
- treatment success,
- adverse events or adverse effects,
- mental health condition, and
- healthcare use.
Investigators searched PubMed, CINAHL, Embase and PsycInfo were searched from inception through Nov. 3, 2020, for peer-reviewed original English-language research that reported the prespecified outcomes of rotation from prescribed long-term opioids to buprenorphine among patients. chronic pain. Risk of bias and study quality were assessed by two independent reviewers who extracted data. Ultimately, 22 studies were analyzed, of which 5 (22.7%) were randomized clinical trials, 7 (31.8%) were case-control or cohort studies, and 10 (45.5%) were uncontrolled pre-post studies. Six of the 22 studies (27.3%) were primary or secondary analyses of a large randomized clinical trial.
The studies involved 1,616 unique participants (675 female [41.8%] and 941 male [58.2%]. With participants reporting varied pain and opioid use histories, rationales for buprenorphine rotation included inadequate analgesia, intolerable adverse effects, risky opioid regimens (e.g., high dose and/or sedative co-prescriptions) and aberrant opioid use. Processes were adapted from protocols for initiating treatment in patients with opioid use disorder, and clinicians usually prescribed buccal or sublingual buprenorphine.
Researchers noted that very low-quality evidence suggested that buprenorphine rotation was associated with maintained or improved analgesia, with a low risk of precipitating opioid withdrawal. They found that steady-dose buprenorphine was better tolerated than tapered-dose buprenorphine.
Essentially, the authors wrote that buprenorphine appeared to be not inferior to full MOR agonists in controlling pain. “Continuing buprenorphine rather than tapering it off was associated with higher rates of protocol completion and lower use of additional opioids,” they added. “Severe AEs were rare, and the adverse effects, although more common, were manageable. The incidence of precipitated opioid withdrawal was low (3%-6%).”
Most of the studies were found to have high risk of bias, however.
“In this systematic review, buprenorphine was associated with reduced chronic pain intensity without precipitating opioid withdrawal in individuals with chronic pain who were receiving LTOT,” the authors concluded. “Future studies are necessary to ascertain the ideal starting dose, formulation, and administration frequency of buprenorphine as well as the best approach to buprenorphine rotation.”
They emphasized that their systematic review “adds to the growing body of literature that suggests that buprenorphine is safe to use in multiple populations, including those with opioid dependence and chronic pain. In contrast, long-term full MOR agonists present significant risks for harmful or fatal overdose, all-cause mortality, and morbidity. Thus, this synthesis supports the hypothesis that rotation from full MOR agonists to buprenorphine would reduce harm, although more research is needed into the best way to complete such rotation.”
- Powell VD, Rosenberg JM, Yaganti A, Garpestad C, Lagisetty P, Shannon C, Silveira MJ. Evaluation of Buprenorphine Rotation in Patients Receiving Long-term Opioids for Chronic Pain: A Systematic Review. JAMA Netw Open. 2021 Sep 1;4(9):e2124152. doi: 10.1001/jamanetworkopen.2021.24152. PMID: 34495339; PMCID: PMC8427372.
