Smith Timothy, Nicholson Robert A
Mercy Health Research, Ryan Headache Center, St. Louis, MO 63141, USA.
Vasc Health Risk Manag. 2007;3(6):833-44.
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.
度洛西汀是一种平衡型选择性5-羟色胺去甲肾上腺素再摄取抑制剂（SNRI），2004年，它成为美国首个获得监管批准用于治疗糖尿病性疼痛性神经病变的药物。除了5-羟色胺和去甲肾上腺素再摄取抑制机制外，该化合物没有其他显著的受体或通道活性，其作用是减轻或控制糖尿病性神经病变的症状。度洛西汀没有已知的神经保护作用或其他可预防糖尿病患者神经病变发生的作用。这篇综述文章的目的是讨论糖尿病性疼痛性神经病变的背景、度洛西汀的药理学，以及它在临床试验和长期观察中的安全性和有效性。作者还将对其在临床实践中的应用发表评论。对照临床试验结果显示，每天服用60毫克或每天两次每次服用60毫克的度洛西汀相对于安慰剂，在治疗糖尿病性神经病理性疼痛方面是有效的。在疼痛和生活质量的其他指标上也观察到了积极的治疗效果。在对照临床试验中，观察到与接受安慰剂治疗的患者相比，血糖有轻微但在统计学上显著的升高。否则，对照和开放标签的临床研究表明该化合物具有高度的安全性和耐受性。这些发现为5-羟色胺和去甲肾上腺素作为脑干和脊髓下行性疼痛抑制途径的关键介质的作用提供了支持。
