Duloxetine: A Balanced and Selective Norepinephrine and Serotonin-Reuptake Inhibitor

Anders D. Westanmo; Jon Gayken; Robert Haight


Am J Health Syst Pharm. 2005;62(23):2481-2490. 

In This Article

Stress Urinary Incontinence

Stress urinary incontinence has a high prevalence in the United States and is associated with a decrease in quality of life.[18] The majority of women over 50 years of age in the United States experience mixed or stress urinary incontinence.[18] Mainstays of therapy have traditionally consisted of pelvic floor muscle training (Kegel exercises) or surgical procedures, while pharmacologic treatment has had little therapeutic benefit and has not been recommended.[57,58] This remains the case today.[59] Traditional pharmacologic therapy, such as adrenergic agents and estrogen, is only marginally effective at controlling symptoms, and surgery, although more effective, is associated with more adverse effects.[60–62] Duloxetine was recently approved in Europe for the treatment of stress urinary incontinence. Although an approvable letter for this indication was issued by FDA in 2003, the application was withdrawn in 2005.[63,64] Despite the lack of an FDA-approved indication, duloxetine adds a new pharmacologic approach and may advance our ability to effectively treat this common problem.

Three randomized, 12-week, placebo-controlled trials have been conducted studying duloxetine 40 mg twice daily in 1635 patients with stress urinary incontinence.[65–67] All analysis was intention to treat, with the LOCF. In these trials duloxetine reduced the median incontinence episode frequency by an amount significantly greater than placebo (50–53.6% versus 27.5–40%; all p < 0.05). In two of the trials the incontinence quality of life (I-QOL) and the patient global impression of improvement (PGI-I) scales were reduced significantly more in patients receiving duloxetine than in those receiving placebo.[65,67] In the third trial, the I-QOL and PGI-I were not different between the duloxetine and placebo groups.[66] The investigators stated that this was due to low scores carried forward from patients who discontinued treatment early due to duloxetine-associated adverse events.[65] Discontinuation rates due to adverse events were significantly higher in patients receiving duloxetine than in those receiving placebo (15–24% versus 2–5%; p <0.05) during clinical trials.[65–68] Nausea was the most frequent adverse event reported and occurred in a greater percentage of patients receiving duloxetine than in those receiving placebo (13–28% versus 2–7%; p <0.05).[63–66] Nausea was usually rated as mild to moderate and often resolved within one to four weeks.