The 2022 Centers for Disease Control and Prevention (CDC) guidelines for prescribing opioids in chronic pain acknowledge the use of buprenorphine in pain management, but primarily makes recommendations for buprenorphine in patients with opioid use disorder who are experiencing acute pain. Buprenorphine dosage forms and use in chronic pain are not discussed. [1]
According to a 2018 systematic review, buprenorphine may exhibit lower rates of constipation and discontinuation versus morphine with comparable chronic pain analgesia. Despite being oral, sublingual buprenorphine tablets demonstrate a bioavailability rate of ~50% relative to parenteral buprenorphine. Peak plasma concentrations occur at 90 mg for sublingual tablets. Newer buprenorphine/naloxone tablets approved by the US in 2013 also deliver greater sublingual bioavailability and faster dissolving rates, but how this translates to pain control is not yet certain. While the buccal formulation has not yet been compared to other opioids, studies have demonstrated pain reduction in opioid tolerant and naïve patients. In general, the studies reviewed suffered from heterogeneity from various qualities of randomized and non-randomized trials as the authors expressed difficulty finding high-quality RCTs. [2], [3]
A 2014 systematic review of 10 studies between 1979-2012 evaluated the efficacy of sublingual buprenorphine (with or without naloxone) for the treatment of chronic pain in 1,190 cancer and noncancer patients. Four studies were general chronic pain while other studies assessed osteoarthritis, sickle-cell disease, nociceptive chronic pain, chronic pain in the elderly, pediatric chronic cancer pain, and cancer chronic pain. Four studies included patients on prior opioid therapy (morphine equivalent daily dose up to 840 mg/day) using SL buprenorphine >400 mcg/dose (high dose). The other 6 studies used SL buprenorphine <400 mcg/dose (low-dose). All studies reported some effectiveness for analgesia in chronic pain. Due to the heterogeneity of the studies, data could not be pooled and findings were described through qualitative syntheses. These outcomes varied in methods to include a decrease in mean pain score using visual analog or numeric rating scales, a narrative description method, and degrees of pain relief including “acceptable”, “Moderate to very good”, and “good to excellent”. For those that reported statistical significance, they demonstrated a decrease in mean pain score by 2.3/10 (p <0.001), 6.6/10 to 2.1/10 (p <0.01), and 2.1/3 to 1.1/3 (p <0.01). Low-dose studies reported a dosing range of 0.1-3.2 mg/day in adults. One RCT of low-dose SL buprenorphine described mean morning pain score decreased from 5.9/10 to 3.1/10 and equivalence of SL buprenorphine 0.2-0.4 mg every 6-8 hours to transdermal buprenorphine 5-20 mcg/h although a higher incidence of nausea, dizziness, and vomiting noted (p <0.05). Various protocols were used in the high-dose SL buprenorphine studies regarding concurrent opioid therapy, all reporting improved pain scores. While SL buprenorphine appeared effective as a chronic pain analgesic, the studies were observational (exception of 1 RCT) with low level of evidence concluding the quality of evidence was not sufficient to provide consensus. [4]
Another 2018 systematic review investigated the efficacy of various buprenorphine formulations, including sublingual buprenorphine tablets. Three included studies investigated the efficacy of SL buprenorphine, generally finding no significant improvement in pain when comparing SL buprenorphine to comparators (memantine, transdermal buprenorphine, and tramadol). None of the included studies compared buprenorphine to placebo, which may hinder true assessment of efficacy. [5]