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AbstractObjective:To evaluate short- and long-term safety and efficacy of duloxetine in women with predominant stress urinary incontinence (SUI).Research design and methods:The study was a 6-week, double-blind, randomised, parallel, placebo-controlled study followed by an uncontrolled open-label extension (OLE) run in 342 study centres in 16 European countries. Women with predominant SUI were randomly assigned to placebo (n1380) or duloxetine 40mg twice daily (n1378) for 6 weeks. Completers of the acute phase were enrolled in the OLE, which had a minimum duration of 6 weeks and ended, based on the approval status of duloxetine in the participating country.Clinical Trial Registry:www.clinicaltrials.gov; NCT00190996.Main outcome measures:The primary outcome measure was the change in incontinence episode frequency (IEF) over 6 weeks. Secondary outcome measures were the long-term maintenance of effect on IEF and Patient Global Impression of Improvement (PGI-I), the short- and long-term impact on quality of life using the Kings Health Questionnaire (KHQ), and the long-term safety of duloxetine.Results:After 6 weeks, the decrease in weekly IEF was significantly greater with duloxetine treatment compared to placebo (−50.0 vs. −29.9; p<0.001). The percentage of responders (defined as 50 decrease in IEF) was significantly higher with duloxetine treatment than with placebo (50.6 vs. 31.2; p<0.001). Duloxetine treatment was associated with improvements in weekly pad use (−31.4), PGI-I ratings (63.6), and KHQ score (−6.25) compared to placebo (−12.5, 48.5 and −3.13, respectively, all p<0.001). Treatment-emergent adverse events were significantly more common during duloxetine treatment (48.3) than placebo (33.3), (p<0.001). Of the 2290 patients continuing into the OLE, 1165 (42.2) completed the available duration, and 592 (21.5) discontinued because of an adverse event (percentages relative to total randomised patients). Long-term efficacy in the OLE was assessed over a 72-week period and was maintained over that time. However, the results should be interpreted within the context that better responding patients are more likely to remain on duloxetine, while patients responding poorly are more likely to discontinue over time.Conclusions:Duloxetine seems to be an efficacious treatment with an acceptable safety profile for women with SUI. Achieved improvement is maintained over the longer term in those women who remain on therapy. [ABSTRACT FROM AUTHOR]

Objective: The safety and tolerability of duloxetine for major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia, and lower urinary tract disorders (LUTD) (including female stress urinary incontinence [SUI] and other LUTDs) has been established in individual clinical studies. The objective of this manuscript is to characterize the overall safety profile of duloxetine, regardless of indication, based on data from the duloxetine exposures integrated safety database.Research design and methods: The duloxetine exposures integrated safety database was examined using pooled data from 23 983 patients randomized to receive duloxetine in 64 studies for MDD, GAD, DPNP, fibromyalgia, or LUTDs. Evaluated aspects of drug safety included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms.Results: Common TEAEs included nausea, headache, dry mouth, insomnia, constipation, dizziness, fatigue, somnolence, diarrhea, and hyperhidrosis. Most TEAEs emerged early; the majority were mild to moderate in severity, and did not worsen. Overall, discontinuation rates due to AEs were 20.0%. SAEs occurred at a rate of 3.5% and no single event was predominant. Mean pulse increased by < 2 beats per minute. Mean increases in systolic and diastolic blood pressure were < 1 mmHg. Mean alanine transaminase and aspartate transaminase values increased by < 2 U/L.Conclusions: The safety profile for the molecule from the overall duloxetine exposures integrated safety database suggests that benign and common pharmacologic side effects occur with duloxetine treatment. Because these pooled analyses do not allow for statistical comparison to placebo or active comparator, and include data from five different studied indications, these data do not suggest causality for AEs, nor are they necessarily generalizable to each disease stated studied. [ABSTRACT FROM AUTHOR]