Review of duloxetine in the management of diabetic peripheral neuropathic pain

Timothy Smith, Robert A Nicholson, Timothy Smith, Robert A Nicholson

Abstract

Duloxetine is a balanced selective serotonin norepinephrine reuptake inhibitor (SNRI) which, in 2004, became the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes. The purpose of this review article is to discuss the background of painful diabetic neuropathy, the pharmacology of duloxetine, and its safety and efficacy in clinical trials and long-term observations. The authors will also comment on its use in clinical practice. Results from controlled clinical trials reveal that duloxetine administered at 60 mg qd or 60 mg bid is efficacious in treating diabetic neuropathic pain relative to placebo. Positive treatment outcomes are also seen for other measures of pain and quality of life. A minor but statistically significant increase in blood glucose compared with placebo treated patients has been observed in controlled clinical trials. Otherwise, controlled and open-label clinical studies have demonstrated a high degree of safety and tolerability for the compound. These findings provide support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.

Figures

Figure 1
Figure 1
Chemical structure of duloxetine.
Figure 2
Figure 2
Primary efficacy measure (24 hour average pain severity score) in duloxetine-treated patients with pain associated with diabetic neuropathy. Reproduced with permission from Goldstein D, Lu Y, Detke MJ et al 2005. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain, 116:109–18. Copyright © IASP®.
Figure 3
Figure 3
Pooled mean change (baseline-week 12) for pain diary scores in duloxetine-treated patients. *Both treatment arms showed significant improvement (p

Figure 4

Pooled mean change (baseline-week 12)…

Figure 4

Pooled mean change (baseline-week 12) for Brief Pain Inventory (BPI) subscales. *Both treatment…

Figure 4
Pooled mean change (baseline-week 12) for Brief Pain Inventory (BPI) subscales. *Both treatment arms showed significant improvement (p

Figure 5

Percentage of patients discontinuing treatment…

Figure 5

Percentage of patients discontinuing treatment per arm.

Figure 5
Percentage of patients discontinuing treatment per arm.

Figure 6

Treatment-emergent adverse events in controlled…

Figure 6

Treatment-emergent adverse events in controlled trials (Goldstein et al 2005; Wernicke et al…

Figure 6
Treatment-emergent adverse events in controlled trials (Goldstein et al 2005; Wernicke et al 2006a, b).

Figure 7

SF-36 scales change from baseline…

Figure 7

SF-36 scales change from baseline in long-term open label studies. *p

Figure 7
SF-36 scales change from baseline in long-term open label studies. *p
All figures (7)
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References
    1. Anderson N, Oren P, Ogura T, et al. Duloxetine enteric pellets. Official Gazette of the United States Patent and Trademark Office Patents. 1996;1185:1954.
    1. Bymaster F, Dreshfield-Ahmad L, Threlkeld P, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes and other neuronal receptors. Neuropsychopharmacology. 2001;25:871–80. - PubMed
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Figure 4
Figure 4
Pooled mean change (baseline-week 12) for Brief Pain Inventory (BPI) subscales. *Both treatment arms showed significant improvement (p

Figure 5

Percentage of patients discontinuing treatment…

Figure 5

Percentage of patients discontinuing treatment per arm.

Figure 5
Percentage of patients discontinuing treatment per arm.

Figure 6

Treatment-emergent adverse events in controlled…

Figure 6

Treatment-emergent adverse events in controlled trials (Goldstein et al 2005; Wernicke et al…

Figure 6
Treatment-emergent adverse events in controlled trials (Goldstein et al 2005; Wernicke et al 2006a, b).

Figure 7

SF-36 scales change from baseline…

Figure 7

SF-36 scales change from baseline in long-term open label studies. *p

Figure 7
SF-36 scales change from baseline in long-term open label studies. *p
All figures (7)
Similar articles
Cited by
References
    1. Anderson N, Oren P, Ogura T, et al. Duloxetine enteric pellets. Official Gazette of the United States Patent and Trademark Office Patents. 1996;1185:1954.
    1. Bymaster F, Dreshfield-Ahmad L, Threlkeld P, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes and other neuronal receptors. Neuropsychopharmacology. 2001;25:871–80. - PubMed
    1. DiVirgilio S, Gonzales C, Knadler M, et al. Effect of duloxetine (DU) on CYP1A2-mediated drug metabolism and the pharmacokinetics (PK) of theophylline (THEO) Clin Pharmacol Ther. 2002;71:63.
    1. Goldstein D, Lu Y, Detke MJ, et al. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116:109–18. - PubMed
    1. Hoke A, Feasby T. Disorders of the peripheral nervous system. In: Humes H, editor. Kelley’s Textbook of Internal Medicine. Philadelphia: Lippincott Williams and Wilkins; 2000. pp. 2980–1.
Show all 24 references
MeSH terms
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 5
Figure 5
Percentage of patients discontinuing treatment per arm.
Figure 6
Figure 6
Treatment-emergent adverse events in controlled trials (Goldstein et al 2005; Wernicke et al 2006a, b).
Figure 7
Figure 7
SF-36 scales change from baseline in long-term open label studies. *p
All figures (7)

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