Abstract
Dear Editor:
Ms. Dankiewicz raises a number of issues with the information provided in our Fast Fact #268 “Low-Dose Buprenorphine Patch for Pain.” First we would like to thank her for pointing out the fact that intravenous buprenorphine is another FDA-approved formulation. In addition, we erred in stating that the Butrans patch is recommended for opioid-tolerant patients only; we agree that it is approved for opioid-naïve patients. Finally, some of the information in our article is not specific to the patch formulation and is based on studies performed with other forms of buprenorphine, because of the limited available data about the buprenorphine patch. Sublingual and intravenous buprenorphine are generally prescribed at higher doses than the Butrans patch.
Risk of respiratory depression with buprenorphine: We agree with Ms. Dandiewicz that there are no head-to-head studies comparing the Butrans patch with other opioids. As with any opioid, buprenorphine can cause respiratory depression, and prescribers should certainly be cautious and warn patients of this risk. However, there is evidence from studies of intravenous and sublingual buprenorphine that this medication causes less respiratory depression than other opioids.1–4 For example, in one double-blinded controlled study, a single 10 mg intramuscular dose of morphine caused small changes in PCO2 and functional residual capacity, while a 0.4 mg dose of sublingual buprenorphine caused no such changes. 2
Buprenorphine side effects: Most resources note typical opioid side effects from buprenorphine, including sedation, constipation, and nausea. However, in particular, a postmarketing surveillance study of the buprenorphine patch found that 1% of patients using buprenorphine experienced constipation, 4% nausea, and 0.8% somnolence, which compares favorably with transdermal fentanyl. 3
Withdrawal symptoms from buprenorphine: We agree that there have not been studies evaluating withdrawal symptoms from the Butrans patch. However, several studies with buprenorphine-maintained patients show mild to moderate withdrawal symptoms from buprenorphine as compared with other opioids.4–6 For example, a 2014 residential, placebo-controlled study of withdrawal symptoms in seven opioid-dependent patients found that withdrawal symptoms after morphine cessation reached a mean of 16 on the Clinical Opioid Withdrawal Scale (COWS) for morphine withdrawal, but no subject scored ≥5 on the COWS (scores ≥5 on the COWS are considered to be clinically significant withdrawal). 5 Other studies have shown the presence of subjective withdrawal symptoms such as anxiety and restlessness, though fewer objective signs such as tachycardia or hypertension. 6 We note that patients receiving buprenorphine maintenance therapy for addiction are generally on higher daily doses of buprenorphine than that available in the Butrans patch, so we would expect the same or fewer withdrawal symptoms from Butrans patch discontinuation.
Recommendation for use of the Butrans patch for mild to moderate pain: Though the FDA indication for the Butrans patch is for moderate to severe pain, this is based primarily on studies of chronic nonmalignant pain. Our review was written for palliative care providers, who often see the most difficult to treat pain. A recent Cochrane review found the average oral morphine doses required for cancer pain of 150–200 mg per day, with a range of 25–2000 mg, 7 while other palliative care populations studied have found averages of 90 mg and 120 mg per day, with ranges up to 5 g morphine per day.8,9 The average patient in these studies could not have been rotated to a Butrans patch, which only can be used for patients taking up to 80 mg of oral morphine equivalent per day. In palliative care populations, we continue to recommend the Butrans patch for mild to moderate pain.