Evaluating the Effects of Buprenorphine Rotation

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Patients with chronic pain may benefit from rotation to buprenorphine.

Rotation to buprenorphine was accomplished successfully in patients with chronic pain who were receiving long-term opioid therapy. Using buprenorphine long term was found to be more successful than tapering off the treatment.

Investigators, led by Victoria D. Powell, MD, Palliative Care Program, Division of Geriatric and Palliative Medicine, University of Michigan, systematically reviewed literature from 22 studies regarding rotation to buprenorphine in individuals with chronic pain who used long-term opioid therapy. 

Overall, adverse effects were mild and very rarely were they severe enough to require discontinuation of buprenorphine.


Long-term opioid use comes with risks even though there are modest improvements in pain and functioning. Some risks include opioid misuse, suppression of immune and endocrine function, and accidental overdose.

Tapering off of long term opioid therapy when risks outweigh benefits can pose a challenge. Some patients experience increased pain and psychological distress. Therefore, rotation to buprenorphine may be a more viable alternative.

Buprenorphine, a partial mu opioid receptor (MOR) agonist, is associated with less respiratory depression, fatal overdose, and overall mortality than full MOR agonists such as morphine sulfate or oxycodone hydrochloride. It also has fewer adverse effects.

According to 4 randomized controlled trials and 6 uncontrolled observational studies, rotation to buprenorphine was associated with little harm to patients.

Adverse effects included headache, gastrointestinal symptoms like nausea, vomiting, constipation, and appetite changes, lightheadedness or dizziness, sedation, and sleep disruption. Transdermal buprenorphine was associated with skin irritation.


In 12 of 17 studies, rotation to buprenorphine displayed a decrease in pain severity. One study for example, Roux et al, stated that at higher doses, buprenorphine treatment was associated with better pain control.

On the McGill Pain Questionnaire, scores significantly decreased under the highest dose condition (OR, 0.42; 95% CI, 0.20-0.90). The median McGill Pain Questionnaire score decreased from 38 to 21  (P < .001) with any dose.

In the remaining 5 studies there was no association between buprenorphine and pain. It was indicated that participants who were rotating from higher doses of full MOR agonists experienced less analgesia after rotation to buprenorphine. However, investigators said the evidence was very low quality.

Investigators found substantial heterogeneity in timing of pain assessments, with some assessing pain immediately after the administration of buprenorphine and other studies assessing pain at the end of the study period. Detailed, validated instruments to assess pain were only used in 7 studies.

The Examined Studies

Of the 22 studies that were reviewed, 5 were randomized clinical trials, 7 were case-control or cohort studies, and 10 were uncontrolled pre-post studies. There was a variety of pain and opioid use among participants.

Reasons for buprenorphine rotation included inadequate analgesia, intolerable adverse effects, risky opioid regimens, and aberrant opioid use. Previously, there hasn’t been much guidance on how to conduct a rotation.

Investigators did a systematic review of literature to synthesize the evidence regarding rotation to buprenorphine from full MOR agonists among individuals undergoing long-term opioid therapy and chronic pain.

This includes the outcomes of precipitated opioid withdrawal, pain intensity, pain interference, treatment success, adverse events or effects, mental health condition, and health care use.

Investigators indicate that future studies are needed to ascertain the ideal starting dose, formulation, and administration frequency of buprenorphine as well as the best approach to buprenorphine rotation.

The study, “Evaluation of Buprenorphine Rotation in Patients Receiving Long-term Opioids for Chronic Pain”, was published in JAMA Network Open.