Transdermal Buprenorphine Relieves Neuropathic Pain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial in Diabetic Peripheral Neuropathic Pain

Abstract

OBJECTIVETo evaluate the efficacy and safety of transdermal buprenorphine in patients with diabetic peripheral neuropathic pain (DPNP). RESEARCH DESIGN AND METHODSThis multicenter, randomized, double-blind, placebo-controlled, parallel-group trial enrolled patients with type 1 or type 2 diabetes and stable glycemic control who had been experiencing moderate to severe DPNP for at least 6 months on maximal tolerated conventional therapy. Patients were randomly assigned to receive buprenorphine (5 mg/h) or placebo patches. The dose was titrated to effect to a maximum of 40 mg/h. Paracetamol was available as rescue analgesia. The severity of pain and other symptoms of DPNP were assessed daily in a patient diary and at clinic visits. RESULTSOne hundred eight-six patients were enrolled, with 93 randomized to either buprenorphine or placebo. A high proportion of patients did not complete the study (buprenorphine 37 of 93, placebo 24 of 93). The main reason for premature withdrawal in the buprenorphine group was adverse events commonly due to untreated nausea and/or vomiting. Among the per-protocol population, more patients in the buprenorphine group (86.3%) experienced a 30% reduction in average versus baseline pain at week 12 than those in the placebo group (56.6%, P < 0.001). A nonsignificant trend favored the buprenorphine group within the intention-to-treat analysis of the same end point (51.7% vs. 41.3%, P = 0.175). CONCLUSIONSTransdermal buprenorphine, when tolerated, is an effective therapy for DPNP and provides another option to manage this challenging painful condition. Nausea and constipation need to be managed proactively to optimize treatment outcomes.

Pharmacotherapeutic Options for Managing Neuropathic Pain: A Systematic Review and Meta-Analysis

“…In the study by Simpson and Wlodarczyk, the buprenorphine patch up to 40 μ g/h was tested in comparison with placebo in patients with diabetic peripheral neuropathy [ 26 ]. A high proportion of patients did not complete the study due to adverse events, and the primary endpoint was not reached.…”

The Safety of Medications used to Treat Peripheral Neuropathic Pain, Part 2 (Opioids, Cannabinoids and Other Drugs): review of Double-Blind, Placebo-Controlled, Randomized Clinical Trials

“…Based on highly evidence-based clinical studies (randomized, double-blind, and placebo-controlled), we selected thirteen clinical studies, between 2000 and today, for our analysis of opioid-induced adverse effects in the treatment of peripheral neuropathic pain (Table 1). These studies included a total of 1582 patients: four of them evaluated tapentadol [15][16][17][18], one fentanyl [19], two oxycodone [20,21], two tramadol [22,23], one buprenorphine [24], two methadone [25,26] and one morphine [27] (Table 1).…”

“…The only study evaluating buprenorphine was conducted by Simpson et al on a total of 186 patients with diabetic neuropathic pain [24]. The dose evaluated was 10-40 µg / h using transdermal patches over 12 weeks.…”

Opioids for chronic non‐cancer neuropathic pain. An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks duration

“…We included one study (Sindrup et al, 2012) which we have missed in the previous review. We included three new studies (Nalamachu, Hale, & Khan, 2014;Simpson & Wlodarczyk, 2016;Vinik et al, 2014) and thus a total of 16 studies with 2,199 participants into the qualitative and quantitative analysis (see Figure 1).…”