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

Abstract

used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF <14 and ≥ 14). Analysis of covariance was used to analyse I-QOL scores. RESULTSThe mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of ≥ 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. CONCLUSIONSThese 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. KEYWORDSstress urinary incontinence, quality of life, duloxetine hydrochloride, serotonin, noradrenaline OBJECTIVESTo further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions,

Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

“…The published articles from these trials stated that adverse events were ascertained through nonprobing questions. [31][32][33][34] All formats of harms data presented MedDRA preferred terms. Narratives were the only format to report verbatim terms.…”

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.…”

“…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.…”

“…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.…”