Duloxetine versus Placebo for the Treatment of North American Women with Stress Urinary Incontinence

Abstract

Six hundred thirty-three women with stress urinary incontinence (SUI) without predominant urge incontinence symptoms were recruited to participate in a double-blind, placebo-controlled, randomized study to investigate the use of duloxetine in the treatment of SUI. This drug is an inhibitor of serotonin and norepinephrine reuptake, which acts by stimulating pudendal motor neurons and increasing striated urethral sphincter contractility. At the time of enrollment, patients underwent the Patient Global Impression Severity rating to establish baseline SUI symptoms and the Beck Depression Inventory-II (BDI-II) to measure baseline depression symptoms. The study included a 2-week lead-in period during which no drugs were given while patients completed a 7-day real-time voiding diary. During a second 2-week period, all participants were given a placebo and completed another 7-day real-time voiding diary. They were then randomized to receive either duloxetine or placebo twice daily for 12 weeks. During this period, patients were seen every 4 weeks and completed a voiding diary for 1 week before each visit. The frequency of incontinence episodes was determined from the diaries. At each visit, patients were evaluated using the Patient Global Impression of Improvement (PGI-I) to determine improvement in SUI symptoms and the Quality of Life Questionnaire (I-QOL) to measure the impact of SUI on social behaviors and interaction. At the end of the 12 weeks, the BDI-II was given again to measure changes in symptoms of depression. There was no difference in demographic or incontinence data between the 2 groups. After the 12-week period, 87% of the participants in the placebo group compared with 63% of those in the duloxetine group were still participating in the study (P <0.001). At least one postrandomization diary was completed by 95% of the placebo group and 83% of the treatment group. Ninety-eight percent and 97% completed an I-QOL, respectively. An intent-to-treat analysis of all patients with at least one postrandomization diary showed a median decrease of 7 incontinence episodes in the duloxetine group compared with a decrease of 3 per week in the placebo group (P <0.001). Over half of participants taking duloxetine experienced a 50% to 100% decrease in incontinence episodes and 10.5% had no episodes compared with 35% and 5.9%, respectively, of women taking placebo (P <0.001 and P <0.05, respectively). The average voiding interval increased significantly for the duloxetine group compared with the placebo group (20 vs. 2 minutes). The duloxetine group had an I-QOL score of 12.1 at the end of the 12-week period compared with 7.2 for the placebo group (P <0.001). Overall, I-QOL scores were 11.1 and 6.8, respectively (P <0.001). Patients receiving duloxetine treatment reported a 62.0% improvement on the PGI-I compared with 39.6% of the women taking placebo (P <0.001). Mean BDI-II scores were normal at both baseline and study completion. Adverse reactions were significantly more common among women taking duloxetine than those taking placebo (Table 1). By the fourth week, nearly all (91%) of the duloxetine group reported nausea symptoms. Most frequently, nausea developed after 2 days of treatment. Symptoms were mild to moderate in severity in 87% of these patients and decreased over time for all except one woman.