What is the role of duloxetine in urinary incontinence treatment?

Updated: Jan 22, 2021
  • Author: Sandip P Vasavada, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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The serotonin/norepinephrine reuptake inhibitor duloxetine is the first drug developed and marketed specifically for stress urinary incontinence. Duloxetine has been approved for the treatment of stress incontinence in Europe, but is not approved for this indication by the US Food and Drug Administration (FDA).

In animal models, duloxetine seems to increase pudendal motor nerve output via increased levels of serotonin and norepinephrine in the pudendal motor nucleus of the sacral spinal segments. As a result, urethral muscular tone and closure pressure is augmented. Similarly, studies in humans suggest that duloxetine enhances urethral closure through neuromodulation of the external urethral sphincter. [64]

A number of clinical trials have demonstrated the efficacy of duloxetine compared with placebo in the treatment of mild and moderate stress incontinence. A small, prospective, double-blind, randomized, placebo-controlled trial demonstrated modest efficacy in patients with severe stress urinary incontinence. [65]

In this study, patients with pure, urodynamically confirmed stress incontinence who were awaiting surgery were treated with duloxetine for 8 weeks. All participants had, on average, 14 or more episodes of stress incontinence per week. Significant improvement was observed in the quality of life indices and in frequency of incontinence episodes and use of protective pads in the patients treated with duloxetine compared with placebo. All positive clinical responses were observed within 2 weeks after initiation of therapy–some as early as 5 days.

The most common side effect was nausea, which tended to decrease with continued use. Discontinuation of therapy was significantly more common in the treatment group, with equal numbers of patients withdrawing because of nausea, vomiting, worsening of hypertension, and headache. Other common side effects included constipation and dry mouth. At the end of the 8-week trial, 20% of the treatment group patients were no longer interested in surgical therapy, versus 0% in the placebo arm.

Another small study demonstrated similar results, with 24% of the patients who received duloxetine declining their planned surgical therapy. Of note, 48% of the patients stopped the medication due to side effects at the 40 mg twice-daily dose schedule used in this study. [66]

A multicenter, double-blind, randomized, placebo-controlled study in 2,758 women with predominant stress incontinence found that after 6 weeks, the decrease in weekly incontinence episode frequency was significantly greater with duloxetine compared with placebo (-50 vs -29.9%). In an uncontrolled, open-label, 72-week extension of the study in 2,290 patients, 21.5% of patients discontinued the drug because of adverse effects. However, the efficacy of duloxetine was maintained in those women who remained on therapy. [67]

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