Ilker Yalcin

Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial.

To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women.

Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence

Objective  To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.

Mixed urinary incontinence symptoms: urodynamic findings, incontinence severity, and treatment response

OBJECTIVE To investigate the relationship between the symptom of mixed urinary incontinence and incontinence severity, urodynamic findings, and treatment response. METHODS This is a secondary analysis of data from 553 women randomized into a double-blind, placebo-controlled study evaluating duloxetine (serotonin–norepi-nephrine reuptake inhibitor) for the treatment of predominant stress urinary incontinence. Assessment variables included incontinent episode frequency, the Incontinence Quality of Life Questionnaire (I-QOL), and the Patient Global Impression of Severity Scale (PGI-S). Urge symptoms were identified with three urge I-QOL questions not included in corrected I-QOL calculations. RESULTS At baseline, 171 women (31%) had mixed urinary incontinence. They had more severe baseline urinary incontinence than did those with stress urinary incontinence (mean incontinent episode frequency 14.3 versus 10.5; PGI-S normal or mild 26.5% versus 70.4%; mean corrected I-QOL 59.1 versus 79.9; all Ps < .001). Baseline urodynamics were performed on a subset of 86 women. Subjects with both urodynamic stress incontinence and detrusor overactivity had less severe incontinence compared with subjects with only urodynamic stress incontinence. Both mixed urinary incontinence and stress urinary incontinence groups had significant decreases in median incontinent episode frequency at a 40 mg per day (62% and 58%, respectively) and 80 mg per day (63% and 65%) duloxetine dose compared with placebo (33% and 44%; all Ps < .05). Response was not dependent on the type of symptoms (interaction P = .47). CONCLUSION For women presenting with predominant stress urinary incontinence symptoms, the major determinant of concurrent urge symptoms was incontinence severity and not the pathophysiologic condition(s) causing the incontinence; duloxetine demonstrated equal efficacy for women with mixed urinary incontinence and pure stress urinary incontinence.

Duloxetine compared with placebo for treating women with symptoms of overactive bladder

To evaluate duloxetine (a serotonin‐noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model.

Validation of a Two-item Quantitative Questionnaire for the Triage of Women With Urinary Incontinence

OBJECTIVE: To evaluate the reproducibility, construct validity, and preferences for the 2-item Stress/Urge Incontinence Questionnaire. METHODS: The questionnaire asks a patient to recall the number of stress urinary incontinence and urge urinary incontinence episodes she experienced during the preceding week. The 4-week prospective study included 3 office visits and enrolled women with stress, urge, or mixed urinary incontinence symptoms. The test–retest reproducibility was assessed after 3 days, and the construct validity of the questionnaire was evaluated against a diary and other measures of incontinence severity and effect. The bother associated with completing (patients) or analyzing (physicians) the diary was assessed. Both groups also reported their time requirements and preferences for the questionnaire or diary. RESULTS: Reproducibility for the classification of symptoms was moderately strong (&kgr; = .536). Test–retest agreement was good (64–80%) for all but balanced mixed incontinence (38%). Intraclass correlations revealed good reproducibility for the number of stress (.694), urge (.703), and total (.726) incontinence episodes. Significant (P < .01) correlations with other measures of incontinence established construct validity. Patients and physicians reported it took less time to complete the questionnaire than the diary, but the majority said the completion or analysis of the diary was of little or no bother and preferred the diary. CONCLUSION: The Stress/Urge Incontinence Questionnaire is a valid tool that can be used in clinical practice to differentiate between symptoms of stress and urge urinary incontinence to make an initial diagnosis, especially in primary care where incontinence is not a focus of the practice. LEVEL OF EVIDENCE: III

DULOXETINE VERSUS PLACEBO FOR THE TREATMENT OF NORTH AMERICAN WOMEN WITH STRESS URINARY INCONTINENCE

PURPOSE Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, increases rhabdosphincter contractility via the stimulation of pudendal motor neuron alpha-1 adrenergic and 5-hydroxytryptamine-2 receptors. In this first phase 3 study we assessed the efficacy and safety of duloxetine in women with stress urinary incontinence (SUI). MATERIALS AND METHODS A total of 683 North American women 22 to 84 years old were enrolled in this double-blind, placebo controlled study. The case definition included a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) of 7 or greater, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress test and stress pad test. After a 2-week placebo lead-in period subjects were randomly assigned to receive placebo (339) or 80 mg duloxetine daily (344) as 40 mg twice daily for 12 weeks. Primary outcome variables included IEF and an incontinence quality of life questionnaire. Van Elterens test was used to analyze percent changes in IEF with a stratification variable of weekly baseline IEF (less than 14 and 14 or greater). ANCOVA was used to analyze incontinence quality of life scores. RESULTS Mean baseline IEF was 18 weekly and 436 subjects (64%) had a baseline IEF of 14 or greater. There was a significant decrease in IEF with duloxetine compared with placebo (50% vs 27%, p <0.001) with comparably significant improvements in quality of life (11.0 vs 6.8, p <0.001). Of subjects on duloxetine 51% had a 50% to 100% decrease in IEF compared with 34% of those on placebo (p <0.001). These improvements with duloxetine were associated with a significant increases in the voiding interval compared with placebo (20 vs 2 minutes, p <0.001) and they were observed across the spectrum of incontinence severity. The discontinuation rate for adverse events was 4% for placebo and 24% for duloxetine (p <0.001) with nausea the most common reason for discontinuation (6.4%). Nausea, which was also the most common side effect, tended to be mild to moderate and transient, usually resolving after 1 week to 1 month. Of the 78 women who experienced treatment emergent nausea while taking duloxetine 58 (74%) completed the trial. CONCLUSIONS These phase 3 data are consistent with phase 2 data and they provide further evidence for the safety and efficacy of duloxetine as a pharmacological agent for the treatment of women with SUI.