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The Role of Buprenorphine in Diabetic Neuropathic Pain

Study finds improvement in pain relief and sleep patterns

Effective management of peripheral neuropathy can be challenging in patients with uncontrolled diabetes. At least 47% of type 1 and type 2 diabetes patients who have both experience peripheral neuropathy and at least 35% of these patients experience painful diabetic neuropathy. Adequate pharmacotherapeutic management of painful peripheral neuropathy relies on utilizing antiepileptic and antidepressant through a decrease in neurotransmission leading to nociception. Agents like pregabalin, gabapentin, amitriptyline, and duloxetine are widely prescribed for management of diabetic neuropathy. However, pregabalin and duloxetine are the agents that the FDA approved for this indication. Recently, more evidence is supporting the use of buprenorphine in diabetic neuropathy due to its pharmacological actions. It has been postulated that the activity of pertussis toxin-sensitive G-protein is reduced in neuropathic pain. Buprenorphine is not affected by levels of activity of this G-protein. Other analgesics acting on the mu opioid receptors depend on this G-protein activity to exert analgesic action. The amount of research on this topic is limited and clinical trials looking into these effects are not widely conducted.

However, Richard W. Simpson and John H. Wlodarcyzk from the Eastern Clinical Research Unit in Box Hill Hospital, Australia conducted a clinical trial where they sought to evaluate the safety and efficacy of transdermal buprenorphine in patients with diabetic peripheral neuropathic pain. This study was a multicenter, randomized, placebo-controlled, parallel-group trial where 186 patients were enrolled to receive buprenorphine patch or placebo patch, however, 61 patients completed the study. Patients were included in this study if they had well-controlled type 1 diabetes and type 2 diabetes for the preceding six months. Additionally, they were included if they experienced diabetic neuropathic pain for a minimum of 6 months on non-opioid analgesic therapy. In addition to the buprenorphine patch, patients were allowed to continue on stable doses of any antidepressants, antiepileptics, or other medications indicated for neuropathic pain that did not entail using weak opioid analgesics, NSAIDs, or any other topical drug and non-drug therapies. The primary endpoint of the study was a 30% reduction in average pain intensity at the end of week 12. Therapy with buprenorphine was started at 5 mcg/hour and titrated to effect on a weekly basis during the first 6 weeks, followed by every 2 weeks from weeks 7-12; max dose of 40 mcg/hour.

Results from this study showed that 51.7% of patients in the buprenorphine group achieved 30% reduction compared to 41.3% in the placebo group (OR 1.56; 95% CI 0.82, 2.97; p=0.175). The most common reported adverse events were nausea, vomiting, and constipation. All of which led some participants to withdraw from the study. One thing to take into consideration in this study is the use of other medications while in the study. Simpson and Wlodarcyzk analyzed the effects of these medications on buprenorphine. The odds ratio for these effects show no meaningful alterations to the efficacy of buprenorphine (antidepressants 0.77; 95% CI 0.39, 1.52 vs antiepileptics 1.48; 95% CI 0.58, 3.81). Furthermore, there was significant change in pain scale scores from baseline (average pain: 5.7) in the buprenorphine group (-1.20 (95% CI 21.83, 20.57; P< 0.001). There was also a significant improvement in sleep in patients receiving buprenorphine when compared to placebo (p<0.05).

In conclusion, the use of the buprenorphine patch in patients with diabetic peripheral neuropathy was able to provide adequate pain relief. This pain relief was determined by significant changes in pain scales and improvements in sleep patterns. The efficacy of buprenorphine does not seem to be affected by the use of other diabetic neuropathy pain medications. Its use is well tolerated and the anticipated adverse effects, associated with opioid use, can be managed through lifestyle and diet changes. Additionally, over-the-counter medication use aids as well in the management of these side effects. Proper patient education and close pain monitoring is needed to ensure optimal pain control and tolerability.

Practice Pearls:

  • Use of buprenorphine should be used as an adjuvant to manage neuropathic pain.
  • Treatment failures are commonly due to adverse effects, such as vomiting, nausea, and constipation, which is also associated with the inability to achieve pain control.
  • Buprenorphine, when used in diabetic neuropathy pain, is associated with improved sleep, which is usually affected by uncontrolled pain.

References:

Simpson, Richard W., Wlodarcyzk, John H. “Transdermal Buprenorphine Relieves Neuropathic Pain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial in Diabetic Peripheral Neuropathic Pain” Diabetes Care 39(9) (2016):1-8. Web.

Wiffen, Philip J., Derry, Sheena, Moore, R Andrew, Stannard, Cathy, Aldington, Dominic, Cole Peter, and Knaggs, Roger. “ Buprenorphine for neuropathic pain”. Cochrane Database of Systematic Reviews. 9 (2015): n. pag. Web.

 

Researched and prepared by Christian Gill, Pharm.D. Candidate, Class of 2017. Reviewed by Michelle Caetano, Pharm.D., BCPS, BCACP, CDOE, CVDOE