A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Neurology (Impact Factor: 8.29). 11/2006; 67(8):1411-20. DOI: 10.1212/01.wnl.0000240225.04000.1a
Source: PubMed


Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord.
To assess the efficacy of duloxetine, a dual reuptake inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP).
In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed.
Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient's Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered.
This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.

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Available from: Joel Raskin
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    • "Duloxetine is the first Food and Drug Administration–approved prescription drug for the management of diabetic peripheral neuropathic pain. As well it is implicated in modulating descending inhibitory pain pathways in the central nervous system (Wernicke et al., 2006). It is a selective and potent dual 5-HT and NE reuptake inhibitor which tends to attenuate pain behavior. "
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    ABSTRACT: Abstract Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Vincristine-induced peripheral neuropathy models showed mixed sensory motor neuropathy. Duloxetine is the first Food and Drug Administration–approved prescription drug for the management of diabetic peripheral neuropathic pain. The present study aimed to explore the dose-dependent effect of duloxetine on vincristine-induced neuropathy in rats. Rats were injected with vincristine (0.1 mg/kg/day) to induce peripheral neuropathy. Treatment with duloxetine (10, 20, 30 mg/kg/day) for six weeks improved behavioural parameters, nociceptive response and nerve conduction velocity. Moreover, histopathology of the sciatic nerve revealed marked improvement in the pathological changes after duloxetine treatment. Also, the high doses of duloxetine (20 or 30 mg/kg) significantly decreased the expression of microglia marker (CD11b). We concluded that duloxetine in high doses can reverse the painful neuropathy induced by vincristine. Spinal microglia involvement may be considered as an assisting mechanism.
    Full-text · Article · Sep 2014
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    • "This rating scale measures patient evaluations of their health change in relation to treatment from “very much improved” to “very much worse” using a visual analogue scale, and has two variants; one for use by the clinician and one for use by the patient. The PGIC has been used in trials of chronic pain [17,18] and recommended as a core outcome measure of global improvement [19]. "
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    ABSTRACT: Patient reports or ratings are essential for measuring the quality of patient care. Measures designed for this purpose tend to focus on the processes and structures of care rather than the outcomes of it. The latter is arguably the most valid indicator of the quality of care patients receive. Typically this information is gathered by probing patient satisfaction with treatment as part of an investigation of satisfaction with hospital care. More recently patient ratings of the outcome of treatment have been obtained to measure treatment efficacy in clinical trials. However, a more direct approach is to ask patients to assess the benefit of treatment on their current health status. We performed a structured literature review on patient reported satisfaction with outcomes of treatment and direct patient assessments of the same. The purpose of this was to identify suitable candidate questions for a short instrument to tap patient evaluations of in-patient hospital interventions. Articles were included if they dealt with patient satisfaction or patient assessment of outcomes of treatment. Articles were excluded if they dealt more generally with patient satisfaction with care. We identified 169 papers, 79 were included in the review. The findings of this review suggest that there are a number of benefits of directly asking patients to assess the outcome of hospital treatment. Importantly this approach reflects outcomes relevant to the patient and is also more likely to reflect patient report in routine clinical practice. There is also evidence that such approaches have face validity and construct validity. The problems associated with this approach (i.e. response bias), are those common to patient reported outcome surveys, but employing appropriate strategies can minimize them. Furthermore, employing a simple set of questions that asks patients to assess outcomes of treatment they receive can be time and resource efficient in comparison to administering lengthy measures. This approach could be tested for potential generic use as an evaluative measure for patients in hospital settings.
    Full-text · Article · Jan 2014 · Health and Quality of Life Outcomes
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    • "Data for these analyses were from duloxetine randomized trials (Table 1), conducted in OA [studies HMFG, HMEP and HMGL (Chappell et al., 2009, 2011; Frakes et al., 2011], fibromyalgia (studies HMBO, HMCA, HMCJ and HMEF (Arnold et al., 2004, 2005; Chappell et al., 2008; Russell et al., 2008) ], CLBP (studies HMEN, HMEO and HMGC (Skljarevski et al., 2009; 2010a, 2010b)), and DPNP [studies HMVAa, HMVAb and HMAW (Goldstein et al., 2005; Raskin et al., 2005; Wernicke et al., 2006) ]. All were randomized, double blind, placebo-controlled studies, conducted in patients with at least moderate initial pain intensity (≥ 4 on a 0–10 numerical rating scale). "
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    ABSTRACT: Background Duloxetine has been studied in four distinct chronic pain conditions - osteoarthritis (OA), fibromyalgia, chronic low back pain (CLBP) and diabetic peripheral neuropathic pain (DPNP). These trials have involved large numbers of patients with at least moderate pain, and have used similar methods for recording pain intensity, over about 12 weeks. Methods Data from the trials were pooled according to painful condition, and reanalysed at the level of the individual patient and using increasing levels of pain intensity reduction (<15%, 15-29%, 30-49%, 50%), with different imputation methods on withdrawal. ResultsThe proportion of patients recording at least 50% pain intensity reduction plateaued after 2-6 weeks in fibromyalgia, and 8-12 weeks in other conditions. The duloxetine-specific benefit [number needed to treat (NNT) for at least 50% pain intensity reduction] was fairly constant after about 2 weeks for DPNP and fibromyalgia and after about 4 or 5 weeks for OA and CLBP. In all conditions, responses were bimodal, with patients generally experiencing either very good or very poor pain relief. Last-observation-carried-forward imputation produced numerically and occasionally statistically better (lower) NNTs than use of baseline-observation-carried-forward (true response). Conclusions Baseline-observation-carried-forward (true response), which combines the success of high levels of pain relief with the failure to experience pain relief on withdrawal of the drug is conservative and probably reflective of clinical practice experience. The distribution of effect was not normal; few patients had the average response and averages are not an appropriate descriptor for these data.
    Full-text · Article · Jan 2014 · European journal of pain (London, England)
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