Decrease In Incontinence Episode Frequency Research Articles

The role of duloxetine in stress urinary incontinence: a systematic review and meta-analysis

This systematic review determined whether the duloxetine can get more benefits versus placebo in managing women with stress urinary incontinence (SUI) all over the world. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing duloxetine with placebo in these patients. The eligible RCTs were identified from the following electronic databases: Cochrane CENTRAL, Medline and EMBASE. We treated the incontinence episode frequency (IEF) as the main outcome, and the secondary outcomes were cured, average voiding interval, incontinence quality of life (I-QOL), treatment-emergent adverse events (TEAEs) and discontinuation. The review contained ten trials including 5,738 women who were randomized to take duloxetine or placebo. All arms in individual trials were comparable for various baseline characteristics. Individual studies showed a significantly greater decrease in IEF than placebo group. The total IEF responders (defined as a woman who had at least a 50 % decrease in IEF with treatment) within the duloxetine-treated women were more than the placebo-treated women (52.5 vs. 33.7 %; RR = 1.56; 95 %CI, 1.46-1.66; p < 0.00001). TEAEs were commonly experienced by both two groups (62.7 vs. 45.3 %) though they were not critical. Our meta-analysis showed that significant efficacy can be found in women treated with a certain dose of duloxetine. The adverse events like nausea, constipation, dry mouth, fatigue etc. are common.

Inpatient bladder retraining: is it beneficial on its own?

Urinary incontinence is a common problem with serious effect on the quality of life. Bladder training aims to increase the interval between voids, either by a mandatory or self-adjustable schedule, so that incontinence is avoided. This study aimed to assess the effectiveness of inpatient bladder retraining. A retrospective case-note analysis was conducted over a period of 24 months. Outcome measures were decrease in incontinence episode frequency (IEF) and nocturia and increase in interval between voids. Subjective improvement was assessed on a four-point scale. The study revealed statistically significant decrease in IEF and nocturia and increase in the interval between voids. Twenty-three percent was cured of their symptoms, 36% reported improvement, 27% did not find any change, whereas 14% reported that they were worse off their after bladder retraining. The study confirms the usefulness of inpatient bladder retraining as a treatment option, especially in people refractory to outpatient management.

Short- and long-term efficacy and safety of duloxetine in women with predominant stress urinary incontinence

Objective: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 (n = 1380) or duloxetine 40 mg twice daily (n = 1378) 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 King’s 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.

Duloxetine in the Treatment of Stress Urinary Incontinence

Objective: To review the available literature regarding the use of duloxetine in the treatment of stress urinary incontinence. Data Sources: Clinical trials were obtained through a PubMed search (1966–December 2004) with the key words duloxetine, urinary incontinence, and stress. Data Synthesis: This article analyzes 5 clinical studies comparing duloxetine with placebo. The randomized, double-blind, multicenter trials were performed in the US and throughout the world and had strict inclusion criteria to enroll only patients with confirmed stess urinary incontinence. All trials showed a statistically significant decrease in incontinence episode frequency of 50–60% for duloxetine compared with a placebo response of 27–40%. Conclusions: Duloxetine appears to be an effective treatment for stress urinary incontinence. Additional trials comparing duloxetine with pelvic floor muscle training would better define duloxetine's place in therapy.

Serotonin and noradrenaline reuptake inhibitors (SNRI) for stress urinary incontinence in adults

To date, standard recommendations for the management of stress urinary incontinence (SUI) would be either pelvic floor muscle training (PFMT) or surgery. A new form of drug treatment with a serotonin-noradrenaline reuptake inhibitor (SNRI), duloxetine, may now have a place in treatment of this condition. To determine whether a SNRI is better than placebo (or no treatment, other pharmacological and non-pharmacological therapies, or surgery) in the treatment of women with SUI, or mixed urinary incontinence that includes stress incontinence (MUI), or both and which doses should be used. We searched the Cochrane Incontinence Group specialised register (searched 1 December 2004), (CENTRAL) (Issue 2, 2004), MEDLINE (January 1966 to September 2004), PREMEDLINE (11 March 2004), Dissertation Abstracts and the reference lists of relevant articles. All randomised or quasi-randomised controlled trials of treatment for SUI or MUI, in which at least one management arm involved a SNRI. Two authors evaluated the trials for appropriateness for inclusion and methodological quality. Three authors performed the data extraction using predetermined criteria. Analyses were performed using the Cochrane Review Manager software, RevMan. Nine randomised trials were included, involving 3327 adults with predominantly SUI, randomised to receive duloxetine or placebo. Both arms in individual trials were comparable for various baseline characteristics. Treatment duration was between three weeks and 12 weeks. Duloxetine was significantly better than placebo in terms of improving patients' quality of life (WMD 5.26, 95%CI 3.84 to 6.68. P< 0.00001) and perception of improvement. Individual studies demonstrated a significant reduction in the Incontinence Episode Frequency (IEF) by approximately 50% during treatment with duloxetine. With regard to objective cure, however, meta-analysis of stress pad test and 24 hour pad weight change failed to demonstrate a benefit for duloxetine over placebo though data were relatively few. Subjective cure favoured duloxetine, albeit with a small effect size (3%). One trial suggested that duloxetine was better than pelvic floor muscle training alone in reducing IEF (P < 0.05) based on median percentage decrease in IEF per week. Although significant side effects were commonly associated with duloxetine, they were reported as acceptable. The available evidence suggests that duloxetine treatment can significantly improve the quality of life of patients with stress urinary incontinence, but it is unclear whether or not benefits are sustainable. Adverse effects are common but not serious. About one in three participants allocated duloxetine reported adverse effects (most commonly nausea) related to treatment, and about one in eight allocated duloxetine stopped treatment as a consequence.

Stress Urinary Incontinence in Women: Efficacy and Safety of Duloxetine

Stress urinary incontinence (SUI), the complaint of involuntary loss of urine on effort or exertion, or on sneezing, coughing or laughing, is a common condition affecting millions of women world wide. SUI is a medical condition which can have a significant impact on the psychosocial, social and economic well-being of the sufferers and their family, thus significantly impairing their Quality of Life (QoL). Currently, women with SUI who wish to have their problem solved can choose between treatments like pelvic floor muscle training, which usually has poor compliance over time, or surgical procedures which are mainly an option for more severely affected patients with the risk of complications. To date, no pharmacological treatment for women with SUI has been widely approved. Duloxetine, a potent and relatively balanced serotonin and noradrenaline reuptake inhibitor, has been evaluated in a clinical trial program of one phase II and three phase III trials world wide, and proven efficacious and safe in the treatment of women with SUI. Significant improvements in various parameters were reported with duloxetine compared to placebo in all trials. Half of the women experienced a median decrease in incontinence episode frequency (IEF) of 50–58%. Concurrent increases in incontinence Quality of Life scores (I-QOL) in the range of 5.5–11.1 points indicated that these improvements in IEF were sufficient for the women to feel noticeably better. Between 56% and 74% of the women treated with duloxetine stated that they felt better after treatment. Nausea was the most common side effect reported in the duloxetine-treated patients; it was usually mild to moderate and transient as it resolved in the majority of the cases in one to four weeks. Overall, duloxetine was well tolerated and efficacious. This drug has the potential to become the first widely approved pharmacological treatment for women with SUI.

The effect of previous treatment experience and incontinence severity on the placebo response of stress urinary incontinence

Objective The placebo response associated with stress urinary incontinence (SUI) is sizeable but poorly understood. The aim of this study was to examine the relationship between previous treatment experience and baseline urinary incontinence severity with placebo response. Study design Nine hundred twenty-one women ages 24 to 83 years received placebo in 4 12-week randomized trials evaluating duloxetine for SUI in 16 countries in Africa, Australia, Europe, and North and South America. Incontinence episode frequency (IEF) was calculated before and after randomization with entries from subject-completed real-time diaries. At baseline, subjects reported on their experience with previous continence surgery and with current pelvic floor muscle training (PFMT) with standardized questions. Analyses included Pearson correlations and the Wilcoxon two-sample test, and were based on intent-to-treat principles. Results The placebo group averaged 17 IEF per week at baseline. Fifty-five percent of placebo-treated subjects averaged ≥14 IEF/wk, 11.8% had previous continence surgery, and 16.5% currently performed PFMT. The overall median decrease in IEF with placebo was 33%, but ranged from 11% to 57% for individual countries. The placebo response was lower in women with more severe SUI (29.6% vs 36.4%, P = .07), in those who had previous continence surgery (25.0% vs 33.3%, P = .26), and for those using PFMT (23.6% vs 33.3%, P = .02). There was a significant positive correlation (rho = .44; P < .0001) between the placebo response within a country and that country's use rate for PFMT. Conclusion Treatment naivete and less severe incontinence are associated with an increased placebo response in clinical trials for stress urinary incontinence, although this difference was statistically significant only for PFMT.

Duloxetine: a new approach for treating stress urinary incontinence

Duloxetine is a potent and balanced dual serotonin and norepinephrine reuptake inhibitor (SNRI) that enhances urethral rhabdosphincter activity and bladder capacity in a cat irritated bladder model. Whether this is beneficial in women suffering from stress urinary incontinence (SUI) has been investigated in one phase 2 and three phase 3 placebo-controlled clinical trials with very comparable inclusion and exclusion criteria and outcome variables. In addition, one phase 3 study was performed in women with SUI awaiting incontinence surgery. These trials involved investigational centers in 5 continents: North America, Europe, Australia, South America and Africa. Duloxetine 80 mg per day (40 mg twice daily) decreased the frequency of incontinence episode frequency (IEF) and improved incontinence-related quality of life (I-QOL) independent of baseline incontinence severity and also in patients awaiting surgery. In the trial in patients awaiting surgery, onset of action was closely monitored and all patients who responded to duloxetine did so within 1–2 weeks. The decrease in IEF and improvement in I-QOL were not due to more frequent voiding, as the mean time between voids increased. Nausea was the most common treatment emergent adverse event. This was mostly experienced early after the start of duloxetine (usually within the first few days) and was usually mild or moderate and non-progressive in severity. The majority of patients reporting nausea continued treatment with duloxetine and in most of these patients the nausea resolved within 1 to 4 weeks. It can, therefore, be concluded that duloxetine 40 mg twice daily is a new and promising pharmacological treatment approach for women with SUI.

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. The study included 458 women aged 27-79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF < 14 and > or = 14). Analysis of covariance was used to analyse I-QOL scores. The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of > or = 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial. These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.

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

To assess the efficacy and safety of duloxetine in women with stress urinary incontinence. Randomised double-blind, placebo-controlled clinical trial. Fort-six centres in seven European countries and Canada. Four hundred and ninety-four women aged 24-83 years identified as having predominant symptoms of stress urinary incontinence using a clinical algorithm that was 100% predictive of urodynamic stress urinary incontinence in a subgroup of 34 women. The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency > or =7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity > or =400 mL and both a positive cough stress test and positive stress pad test. Subjects completed two urinary diaries prior to randomisation and three diaries during the active treatment phase of the study, each completed during the week prior to monthly visits. Subjects also completed quality of life questionnaires at each visit. Safety was assessed by the evaluation of treatment-emergent adverse events, discontinuation of treatment because of adverse events, serious adverse events, vital sign measurements, electrocardiograms (ECG) and clinical laboratory tests. After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks. The percentage decrease in incontinence episode frequency and the change in the Incontinence Quality of Life (I-QOL) questionnaire total score were prespecified as co-primary outcome variables in the protocol. Incontinence episode frequency decreased significantly with duloxetine compared with placebo (median decrease of 50%vs 29%; P= 0.002) with comparable improvements in the more severely incontinent subgroup (those experiencing at least 14 incontinence episodes per week at baseline; 56%vs 27% decreases; P < 0.001). The primary analysis of I-QOL scores did not reveal a significant difference between treatment groups, due primarily to the carrying forward of low scores from patients who discontinued treatment very early due to duloxetine-associated adverse events. The increase in I-QOL scores was significantly greater for duloxetine than for placebo at each of the three postrandomisation visits after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events were higher for duloxetine (22%vs 5%; P < 0.001) with nausea being the most common reason for discontinuation (5.3%). Nausea tended to be mild to moderate, not progressive, and transient. The findings support duloxetine as a potential treatment for women with stress urinary incontinence.

Duloxetine Versus Placebo for the Treatment of North American Women With Stress Urinary Incontinence

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). 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 Elteren's 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. 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. 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.