Potential for the first pharmaceutical treatment to reduce incontinence episode frequency and improve quality of life for stress urinary incontinence sufferers.

Women with stress urinary incontinence using duloxetine experienced significant reductions in the frequency of incontinence episodes and a significant improvement in quality of life compared to women taking placebo, according to a study published in the July issue of the American Journal of Obstetrics and Gynecology (AJOG) Norton P; Zinner N; Yalcin I; Bump R; Duloxetine versus placebo in the treatment of stress urinary incontinence, American Journal of Obstetrics & Gynecology; July 2002.

If further studies confirm these data, and if it is approved for use by regulatory agencies, duloxetine could become the first pharmaceutical treatment indicated to reduce the frequency of stress urinary incontinence episodes.

Stress incontinence is the most prevalent form of incontinence in women Sandvik H. et al: Diagnostic Classification of Female Urinary Incontinence:

An Epidemiological Survey Corrected for Validity. J Clin Epidemiol Vol. 48. No 3. pp. 339-343. 1995. It is an involuntary leakage of urine in response to any physical activity that raises intra-abdominal pressure, such as coughing, sneezing, bending down and any exercise.

Duloxetine 80mg, taken at 40 mg twice a day, reduced the frequency of incontinence episodes by at least 64 percent in half of the women in the duloxetine arm (n= 140) of the study, compared with a 41% median reduction seen in the placebo group. Duloxetine also demonstrated a similar reduction in incontinence episode frequency among a subset of 163 women with more severe incontinence (those experiencing at least 14 incontinence episodes/week). Despite the increased severity of their condition, these subjects, achieved the same reduction in incontinence episode frequency (IEF) with duloxetine as women with less severe incontinence, at the 80mg dose.

"These data are very encouraging and provide evidence to support duloxetine as a potential pharmaceutical treatment for stress urinary incontinence," said Professor Linda Cardozo, Professor of Urogynaecology at King's College Hospital, London. "Current treatment options are limited to pelvic floor muscle exercises, surgery and devices, so potentially, duloxetine could offer a new treatment option for the significant number of women with this condition."

In this study, patients on duloxetine also reported improvements on scales used to measure effects on their quality of life. Patients responded to a condition-specific questionnaire designed to measure improvement in their condition. Forty-four percent of those taking duloxetine 80mg reported feeling "very much better" or "much better", compared with 27% reporting the same on placebo.

Safety
Duloxetine was generally well tolerated. According to the study authors, none of the adverse events reported, which were related to the study drug, were considered to be clinically severe. Nausea was the most commonly experienced event, and was reported by 13% of patients taking 80mg daily of duloxetine, compared with 2% taking placebo. Fifteen percent of patients taking 80 mg daily of duloxetine stopped taking the drug, compared with 5% taking placebo.

Study methodology
The Phase II data are derived from a double blind, randomized, placebo-control clinical trial conducted at 48 centers in the United States, among 553 women aged 18-65. All women had a predominant symptom of stress urinary incontinence of a least four episodes per week, for up to

three months. The primary measure used by researchers focused on decreases in the incontinence episode frequency that were recorded real-time by patient diaries. Additional measures included the Patient Global Impression of Improvement (PGI-I) Scale, and an I-QOL Questionnaire.