Norton Peggy A, Zinner Norman R, Yalcin Ilker, Bump Richard C
Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, USA.
Am J Obstet Gynecol. 2002 Jul;187(1):40-8. doi: 10.1067/mob.2002.124840.
The purpose of this study was to assess the efficacy and safety of duloxetine, a selective inhibitor of serotonin and norepinephrine reuptake, in the treatment of stress urinary incontinence.
A double-blind, randomized, placebo-controlled study was conducted in 553 women aged 18 to 65 years with a predominant symptom of stress urinary incontinence. Subjects were randomized to placebo (n = 138 women) or duloxetine at one of three doses (20 mg/d, n = 138 women; 40 mg/d, n = 137 women; or 80 mg/d, n = 140 women). Outcome variables that were assessed after 12 weeks of treatment included incontinence episode frequency recorded in a real-time diary and answers provided to the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire.
Duloxetine was associated with significant and dose-dependent decreases in incontinence episode frequency that paralleled improvements that were observed in the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire. The median incontinence episode frequency decrease with the use of the pooled diary analysis with placebo was 41% compared with 54% for duloxetine 20 mg per day (P =.06), 59% for duloxetine 40 mg per day (P =.002), and 64% for duloxetine 80 mg per day (P <.001). One half of the subjects at the 80 mg per day dose had a > or = 64% reduction in incontinence episode frequency (P <.001 vs placebo); 67% had > or = 50% reduction (P =.001 vs placebo). These improvements were observed despite significant concurrent dose-dependent increases in the average voiding interval in the duloxetine groups compared with the placebo group. Similar statistically significant improvements were demonstrated in a subgroup of 163 subjects who had more severe stress urinary incontinence (> or = 14 incontinence episode frequency per week; 49%-64% reduction in incontinence episode frequency in the duloxetine groups compared with 30% in the placebo group). Discontinuation rates for adverse events were 5% for placebo and 9%, 12%, and 15% for duloxetine 20, 40, and 80 mg per day, respectively (P =.04). Nausea was the most common symptom that led to discontinuation. None of the adverse events that were reported were considered to be clinically severe.
This trial provides evidence for the efficacy and safety of duloxetine as a pharmacologic agent for the treatment of stress urinary incontinence.
本研究旨在评估5-羟色胺和去甲肾上腺素再摄取抑制剂度洛西汀治疗压力性尿失禁的有效性和安全性。
对553例年龄在18至65岁、以压力性尿失禁为主要症状的女性进行了一项双盲、随机、安慰剂对照研究。受试者被随机分为安慰剂组(138例女性)或度洛西汀三个剂量组之一(20mg/d,138例女性;40mg/d,137例女性;或80mg/d,140例女性)。治疗12周后评估的结果变量包括实时日记中记录的尿失禁发作频率,以及患者总体改善印象量表和尿失禁生活质量问卷的回答。
度洛西汀与尿失禁发作频率显著且剂量依赖性降低相关,这与患者总体改善印象量表和尿失禁生活质量问卷中观察到的改善情况一致。与安慰剂组合并日记分析相比,使用安慰剂时尿失禁发作频率的中位数降低了41%,而度洛西汀20mg/d组为54%(P = 0.06),度洛西汀40mg/d组为59%(P = 0.002),度洛西汀80mg/d组为64%(P < 0.001)。80mg/d剂量组中有一半的受试者尿失禁发作频率降低≥64%(与安慰剂组相比,P < 0.001);67%的受试者降低≥50%(与安慰剂组相比,P = 0.001)。尽管度洛西汀组与安慰剂组相比平均排尿间隔有显著的同时性剂量依赖性增加,但仍观察到了这些改善。在163例压力性尿失禁更严重(每周尿失禁发作频率≥14次;度洛西汀组尿失禁发作频率降低49%-64%,而安慰剂组为30%)的受试者亚组中也显示出类似的统计学显著改善。安慰剂组不良事件停药率为5%,度洛西汀20、40和80mg/d组分别为9%、12%和15%(P = 0.04)。恶心是导致停药的最常见症状。报告的不良事件均未被认为具有临床严重性。
本试验为度洛西汀作为治疗压力性尿失禁的药物的有效性和安全性提供了证据。