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

Abstract

Objective To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.Design Randomised double-blind, placebo-controlled clinical trial.Setting Fort-six centres in seven European countries and Canada.Population 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. Methods The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency !7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity !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. Intervention After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks. Main outcome measures 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. Results 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. Conclusions The findings support duloxetine as a potential treatment for women with stress urinary incontinence.

Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence

“…57,117,128,[130][131][132][133][134][136][137][138][139][140][141][142][143][144][145]189 Twelve of these involved drug therapy and used a placebo to blind participants. 57,117,[136][137][138][139][140][141][142][143][144][145] In the other seven studies, participants were blinded through sham ES, [130][131][132][133][134]189 or imitation or placebo PFMT. 57,128 Six studies (6.8%) reported that health-care providers were blinded.…”

Tolerability and efficacy of duloxetine in a nontrial situation

“…This was worse than those reported in the pooled analysis from the Phase 3 randomised placebocontrolled studies on a worldwide scale, which was 75%. [6][7][8][9] Interestingly a similar number of women with mixed incontinence and USI had a PGI-I score indicating improvement. This suggests that there may be a role for duloxetine in the treatment of women with mixed incontinence.…”

“…16 Duloxetine trials suggest benefit in the treatment arm of between 49-65% and low discontinuation rates due to adverse effects (22%). [6][7][8][9] A Cochrane review reports that duloxetine significantly improved the QoL of patients with SUI. 17 The review reported that one in eight women stopped duloxetine due to adverse effects.…”

“…Pooled data analysis from randomised, double-blind placebo-controlled trials on duloxetine, has shown duloxetine to be significantly more effective than placebo in reducing incontinence episode frequency (IEF) and improving QoL scores. [6][7][8][9] Inhibition of 5H-T and NA reuptake is not only the basis of duloxetine's efficacy but also the cause of its adverse effects. The most common adverse effect is nausea and was reported to have a prevalence of 23% in the above trials.…”

“…The most common adverse effect is nausea and was reported to have a prevalence of 23% in the above trials. [6][7][8][9] Nausea, dizziness, fatigue and insomnia (1-6%) were the most common adverse event-related reasons for discontinuation. The revised guidelines of the International Consultation on Incontinence recommend complementing conservative therapy with appropriate drug therapy for the initial management of women with SUI.…”