Duloxetine vs. placebo in patients with painful diabetic neuropathy

Abstract

The aim of this study was to examine the efficacy and safety of duloxetine, a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, in the management of diabetic peripheral neuropathic pain. Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways. In a 12-week, multicenter, double-blind study, 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/d (20 mg QD), 60 mg/d (60 mg QD), 120 mg/d (60 mg BID), or placebo. The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument. The primary efficacy measure was the weekly mean score of the 24-h Average Pain Score, which was rated on an 11-point (0-10) Likert scale (no pain to worst possible pain) and computed from diary scores between two site visits. Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo on the 24-h Average Pain Score, beginning 1 week after randomization and continuing through the 12-week trial. Duloxetine also separated from placebo on nearly all the secondary measures including health-related outcome measures. Significantly more patients in all three active-treatment groups achieved a 50% reduction in the 24-h Average Pain Score compared with placebo. Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events. Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain.

Duloxetine versus Routine Care in the Long-Term Management of Diabetic Peripheral Neuropathic Pain

“…In a randomized, controlled, 12-week trial comparing duloxetine 60 mg once daily (QD) and duloxetine 60 mg twice daily (BID) or duloxetine 20 mg QD with placebo in 457 patients with DPNP and without depression, duloxetine was found to be effective and safe for DPNP management. 27 Based on this evidence, two more independent 12-week acute therapy studies were conducted, and these studies confirmed the safety and efficacy of duloxetine 60 mg QD and 60 mg BID in the management of patients with DPNP. 28,29 The study presented here was conducted in order to evaluate the safety, as well as the impact of therapy on patient-reported health outcomes with up to 65 weeks exposure with duloxetine 60 mg BID or routine care.…”

“…[27][28][29] In these studies, duloxetine 60 mg QD and 60 mg BID demonstrated significant improvement compared to placebo on the 24-hour average pain severity score. In addition, patients who completed one of the 12-week acute therapy phase studies were rerandomized to duloxetine 60 mg BID or routine care for 52 weeks of open-label treatment in order to evaluate the safety of duloxetine over long-term administration.…”

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…The literature regarding SNRI use for the prevention of chronic post-surgical pain is limited; however, given that the SNRI medication (duloxetine) is a firstline medication for the treatment of chronic neuropathic pain [67], its role in the prevention of chronic post-surgical pain should be further investigated. Duloxetine has been shown to be efficacious for the treatment of diabetic peripheral neuropathy and fibromyalgia [68][69][70][71]. Appropriately powered trials are necessary to examine the efficacy of the SNRIs in CPSP prevention, including dose-response studies and head-to-head comparisons with other drugs, such as pregabalin.…”

Pharmacotherapy of Fibromyalgia: Focus on Duloxetine

“…31,32 In patients with painful diabetic neuropathy, duloxetine with a dose of 120 mg/day could be appropriate for these patients who require additional pain relief. 48 These doses may be useful in depression or anxiety, for example with 18.28% patients taking 120 mg/day in a general anxiety disorder study with flexible dosing. 49 In cases of efficacious dosing, in agreement with the presented studies, it is possible to stop duloxetine after 3 to 6 months, and eventually 12 months.…”