Duloxetine versus Placebo for the Treatment of North American Women with Stress Urinary Incontinence

Dmochowski, Roger R.; Miklos, John R.; Norton, Peggy; Zinner, Norman R.; Yalcin, Ilker; Bump, Richard C.

doi:10.1097/01.ogx.0000116046.42679.18

Cited by 66 publications

(149 citation statements)

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“…Stress urinary incontinence (SUI) a¡ects nearly 30 million American women [Dmochowski et al, 2003]. Based on the observation that disruption of the sympathetic or the somatic innervation of the bladder outlet can result in neurogenic sphincter incompetence, investigators have determined that bladder neck and urethral smooth muscle tone is partly dependent on alpha-adrenergic activity [Deplanne et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

The role of angiotensin II in stress urinary incontinence: A rat model

Phull

Salkini

Escobar

et al. 2006

Neurourology and Urodynamics

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Aims: Pharmacological treatment for stress urinary incontinence (SUI) is limited to the use of nonselective alpha-agonists, which are often ine¡ective. Non-adrenergic mechanisms have also been implicated in urethral closure, including angiotensin II (Ang-II), which has been demonstrated throughout the urinary tract. We investigate the role of Ang-II in urethral tone in a rat model of SUI. Methods: Abdominal leak point pressure (ALPP) and retrograde urethral pressure pro¢lome-try (RLPP) were measured in 70 female virgin rats. Thirty rats underwent pudendal nerve injury (PNT), 30 had circumferential urethrolysis (U-Lys), and 10 had sham surgery. Rats received daily doses of Angiotensin Type 1 (AT-1) receptor inhibitor (20 mg/kg), Angiotensin Type 2 (AT-2) receptor antagonist (10 mg/kg), or Ang-II (2 mg/kg). Results: Following U-Lys, RLPP and ALPP decreased from 21.4 AE 2.0 and 39.2 AE 3.3 mm Hg, to 13.1 AE1.5 and 21.6 AE 1.9 mmHg, respectively (P<0.01). After PNT, RLPP, and ALPP decreased from 21.0 AE 1.6 and 41.9 AE 3.0 mmHg to 13.1 AE1.5 and 24.7 AE 3.3 mmHg, respectively (P<0.01). AT-1 inhibitor caused signi¢cant decrease in RLPP and ALPP from 21.0 AE 6.2 and 41.8 AE 9.4 mmHg, to 12.0 AE 3.8 and 25.6 AE 6.6 mmHg, respectively (P<0.01). Likewise, AT-2 treatment reduced RLPP and ALPP from 21.4 AE 6.3 and 40.1 AE1.7 mmHg, to 13.5 AE 5.7 and 31.0 AE 7.2 mmHg, respectively (P<0.01). Following surgery, Ang-II administration restored RLPP and ALPP to baseline presurgical values. Conclusions: AT-1 and AT-2 receptor inhibition signi¢cantly lowers urethral resistance, comparable to either neurogenic or urethrolytic injury. Ang-II treatment restored urethral tone in rats with intrinsic sphincter dysfunction. Ang II appears to serve a functional role in the maintenance of urethral tone and stress continence.

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Section: Introductionmentioning

confidence: 99%

The role of angiotensin II in stress urinary incontinence: A rat model

Phull

Salkini

Escobar

et al. 2006

Neurourology and Urodynamics

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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Tolerability and efficacy of duloxetine in a nontrial situation

Duckett¹,

Vella²,

Kavalakuntla³

et al. 2007

BJOG

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Objective To assess the tolerability and efficacy of duloxetine in a nontrial situation.Design Prospective observational study.Setting Urogynaecology Unit, District General Hospital, UK.Population Two hundred and twenty-two women with a diagnosis of urodynamic stress incontinence (USI) or mixed USI and detrusor overactivity (DOA) took duloxetine for 4 weeks. MethodsThe results of therapy were assessed with a Patient Global Impression of Improvement (PGI-I) questionnaire. One hundred and forty-eight (67%) women were initially treated with 40 mg twice a day, 67 (30%) women were treated with an escalating dose initially at 20 mg twice a day increasing to 40 mg twice a day after 2 weeks and seven (3%) women were started on a dose of 20 mg twice a day which they continued.Main outcome measures Discontinuation rates and PGI-I scores.Results Overall 146/222 (66%) women discontinued therapy due to adverse effects or lack of efficacy. Significantly more women starting on the 40 mg twice a day dose stopped due to adverse effects when compared with the escalating dose (P < 0.025). Of the women who tolerated therapy, 80 out of 120 (67%) had a PGI-I score indicating an improvement. However, the overall rate of improvement was 37%. PGI-I scores and discontinuation rates were not significantly different between the group with USI and the group with mixed USI and DOA (P > 0.05).Conclusion In a nontrial situation duloxetine is poorly tolerated. Introducing an escalating dose may improve tolerability. A similar number of women with USI and mixed incontinence had a PGI-I score indicating improvement.Keywords Detrusor overactivity, duloxetine, mixed incontinence, urodynamic stress incontinence.Please cite this paper as: Duckett J, Vella M, Kavalakuntla G, Basu M. Tolerability and efficacy of duloxetine in a nontrial situation. BJOG 2007;114:543-547.

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