Pharmacotherapy for stress urinary incontinence : present and future options

Abstract

Stress urinary incontinence (SUI) is the accidental leakage of urine associated with physical activities such as running, jumping or lifting, or with sneezing and coughing. Worldwide, SUI is a highly prevalent condition, both in young and elderly women, and is a condition fraught with social isolation, loss of self-esteem and significant financial burden. Most women with SUI assume that it is an inevitable part of aging and "suffer in silence", relying on absorbent pads or lifestyle changes to cope with their condition.Unfortunately, for those who do seek medical treatment, the absence of effective and well tolerated pharmacological treatments for SUI limits the clinician's choices to behavioural modification, biofeedback and surgery. Many of the nonsurgical approaches have low success rates, particularly in the elderly and more severely afflicted. Although most continence surgeries have been reported to produce very high cure rates, many women are willing to live with their condition rather than undergo such invasive options. In an attempt to help these patients, some physicians prescribe off-label agents, including tricyclic antidepressants such as imipramine, alpha- and beta-adrenoceptor agonists, and estrogen replacement therapy. The use of these therapies has been limited by unpredictable results and adverse reactions. In addition, acetylcholine receptor antagonists are often prescribed for SUI, despite the fact that these medications have never been shown to be effective in this condition. This lack of a reliable pharmaceutical agent led to the development of duloxetine, a balanced dual reuptake inhibitor of serotonin and norepinephrine that is also being studied for the treatment of major depressive disorder. Based on in vivo data in animals, duloxetine is believed to increase the strength of urethral sphincter contractions and, thereby, prevent accidental urine leakage by increasing urethral closure forces. In clinical trials in women with SUI, duloxetine has demonstrated efficacy in reducing incontinence episodes and increasing the quality of life with no serious adverse effects. Nausea was the most common adverse event; however, in most patients it was reported early in treatment, mild-to-moderate in severity and transient. A medication such as duloxetine, if approved, would go a long way towards expanding the available treatment options for patients with SUI.