Clinical experience with desvenlafaxine in treatment of pain associated with diabetic peripheral neuropathy

Abstract

Purpose: To assess the safety and efficacy of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine in adults with painful diabetic peripheral neuropathy (DPN).

Clinicaltrialsgov identifiers: NCT00283842, NCT01050218.

Patients and methods: This was a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study of desvenlafaxine in adults with painful DPN. The primary efficacy endpoint was change from baseline in numeric rating scale (NRS) score. Patients who completed the 13-week trial could continue in a 9-month open-label, flexible-dose extension study.

Results: A total of 412 patients were randomized to treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/day. Of those, 240 patients continued in the extension study. After a planned interim analysis, conducted when the first 225 patients had completed 6 weeks of treatment in the short-term study, randomization to the 50 mg or 400 mg doses was stopped. At week 13, the mean change from baseline in NRS score was significantly greater compared with placebo in the desvenlafaxine 200 mg (difference [95% confidence interval {CI}]: 1.10 [0.50 to 1.70]; P<0.001) and 400 mg groups (0.91 [95% CI: 0.23 to 1.59]; P=0.027); differences from placebo were not statistically significant for the 50 mg (0.58 [95% CI: -0.08 to 1.25]) and 100 mg (0.59 [95% CI: -0.03 to 1.21]) groups. Nausea and dizziness were the most common treatment-emergent adverse events reported in the short-term study, and the most common adverse events leading to discontinuation in the short-term study and the extension. Adverse events rates were dose-dependent in the short-term studies.

Conclusion: Desvenlafaxine was effective in relieving pain associated with DPN at doses of 200 and 400 mg/day, and improved activity impairment at all doses assessed. Desvenlafaxine was generally well-tolerated in the short-term and long-term studies.

Keywords: adaptive study design; diabetic neuropathy; efficacy; neuropathic pain; safety; serotonin-norepinephrine reuptake inhibitor.

Figure 1

Study flowchart. Abbreviation: ITT, intent-to-treat.

Figure 2

Adjusted mean change from baseline on NRS pain severity over time (ITT; MMRM). Notes: ^aP=0.084 (Hochberg) for desvenlafaxine 50 mg and 100 mg groups versus placebo; ^bP=0.027 (Hochberg) for desvenlafaxine 400 mg versus placebo; ^cP=0.001 (Hochberg) for desvenlafaxine 200 mg versus placebo. Abbreviations: ITT, intent-to-treat; MMRM, mixed-effects model for repeated measures; NRS, numeric rating scale.

Figure 3

Response rate on pain severity score on the NRS at week 13 (ITT). Notes: ^aNRS response is defined as a reduction of 50% or more from baseline; ^bno significant differences from placebo for active treatment groups. Abbreviations: ITT, intent-to-treat; NRS, numeric rating scale.

Figure 4

Proportions of patients achieving minimum thresholds of reduction in NRS score at week 13 (ITT). Abbreviations: ITT, intent-to-treat; NRS, numeric rating scale.