May Wakamatsu, MD

THE QUESTION:
Is duloxetine hydrochloride effective in the treatment of stress urinary incontinence (SUI)?

Past studies

Research has indicated that the neurotransmitters serotonin and norepinephrine are responsible for neural control of the lower urinary tract. Serotogenic agonists generally suppress parasympathetic activity and enhance sympathetic and somatic activity in the lower urinary tract—effects that promote urine storage.

This study

This double-blind, randomized, placebo-controlled study examined 553 women, ages 18 to 65, with at least a 3-month diagnosis of SUI. Subjects were assigned a 12-week course of either placebo (n=138) or duloxetine treatment at 1 of 3 daily doses: 20 mg (n=138), 40 mg (n=137), or 80 mg (n=140). The women were examined once every 4 weeks and asked to keep a diary documenting voiding episodes.

The diary entries revealed a decrease in incontinence episodes for all subjects. Patients taking placebo recorded a 41% decline, compared to 54% in women taking 20 mg/d of duloxetine, 59% for users on 40 mg of duloxetine, and 64% for women taking 80 mg of duloxetine. Among women taking the 80-mg dose, half experienced at least a 64% reduction in incontinence frequency and 67% noted at least a 50% decrease.

Researchers concluded that duloxetine is a safe and effective agent for treating SUI.

Find this study

Norton PA, Zinner NR, Yalcin I, Bump RC. July 2002 issue of American Journal of Obstetrics and Gynecology; abstract online at www3.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

Women suffering from SUI.

Expert commentary

The annual direct cost of female urinary incontinence in the United States is approximately $12.4 billion,¹ with $1.3 billion dedicated to treatment. Of that, surgical management accounts for nearly 80% (or $1 billion), while pharmacologic therapy utilizes only 9% ($114 million).¹ Thus, even with rising medication costs, medical incontinence management uses fewer health-care dollars than surgery. If more women can be effectively treated pharmacologically, therefore, we can conserve valuable health-care resources while reducing related costs, such as time off from work.

If more women can be treated pharmacologically, we can conserve valuable health-care resources.

Presently, there are agents available to treat urge incontinence, but no effective, tolerable medical therapies for stress incontinence. Alpha-1 agonists such as pseudoephedrine have been used for SUI, but the side effects of nervousness, dizziness, and insomnia have proved prohibitive.

SUI typically is treated either surgically or with physical therapy designed to strengthen pelvic-floor muscles. Recently, however, advances in the understanding of neuromuscular control of women’s “stress continence control system” has spurred the development of new drugs.²

In this study, duloxetine use was associated with significant decreases in incontinent episodes (as measured by diary entries). Quality-of-life measures also improved significantly. In addition, voiding intervals lengthened, indicating that women were not voiding more frequently to avoid incontinent episodes. This result may indicate duloxetine’s dual efficacy with the continence system: increasing bladder capacity and increasing striated urethral sphincter activity. A more recent analysis of a subgroup of patients with both stress and urge incontinence showed similar improvements.³

Interestingly, cough stress tests at 400 mL and pad tests failed to demonstrate any significant improvement in the study’s treated patients. However, these conflicting results may reflect inherent problems with assessing urinary incontinence treatments: A patient with 400 mL of urine in her bladder may leak with vigorous coughing in the upright position, but if she voids at 300 to 350 mL—a reasonable bladder capacity—she may never leak in “real life.”

Bottom line

Duloxetine hydrochloride appears to be a promising new pharmacologic agent to treat stress incontinence. However, clinicians must keep in mind that even when drugs seem efficacious in clinical trials, they may not yield the same results in clinical practice. Patients in this study completed weeklong diaries every 4 weeks, which, by itself, may improve bladder csontrol.

As mentioned by the authors, larger multinational trials are needed to further demonstrate duloxetine’s safety and efficacy in more diverse clinical settings.

THE QUESTION:
Is duloxetine hydrochloride effective in the treatment of stress urinary incontinence (SUI)?

Past studies

Research has indicated that the neurotransmitters serotonin and norepinephrine are responsible for neural control of the lower urinary tract. Serotogenic agonists generally suppress parasympathetic activity and enhance sympathetic and somatic activity in the lower urinary tract—effects that promote urine storage.

This study

This double-blind, randomized, placebo-controlled study examined 553 women, ages 18 to 65, with at least a 3-month diagnosis of SUI. Subjects were assigned a 12-week course of either placebo (n=138) or duloxetine treatment at 1 of 3 daily doses: 20 mg (n=138), 40 mg (n=137), or 80 mg (n=140). The women were examined once every 4 weeks and asked to keep a diary documenting voiding episodes.

The diary entries revealed a decrease in incontinence episodes for all subjects. Patients taking placebo recorded a 41% decline, compared to 54% in women taking 20 mg/d of duloxetine, 59% for users on 40 mg of duloxetine, and 64% for women taking 80 mg of duloxetine. Among women taking the 80-mg dose, half experienced at least a 64% reduction in incontinence frequency and 67% noted at least a 50% decrease.

Researchers concluded that duloxetine is a safe and effective agent for treating SUI.

Find this study

Norton PA, Zinner NR, Yalcin I, Bump RC. July 2002 issue of American Journal of Obstetrics and Gynecology; abstract online at www3.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

Women suffering from SUI.

Expert commentary

The annual direct cost of female urinary incontinence in the United States is approximately $12.4 billion,¹ with $1.3 billion dedicated to treatment. Of that, surgical management accounts for nearly 80% (or $1 billion), while pharmacologic therapy utilizes only 9% ($114 million).¹ Thus, even with rising medication costs, medical incontinence management uses fewer health-care dollars than surgery. If more women can be effectively treated pharmacologically, therefore, we can conserve valuable health-care resources while reducing related costs, such as time off from work.

If more women can be treated pharmacologically, we can conserve valuable health-care resources.

Presently, there are agents available to treat urge incontinence, but no effective, tolerable medical therapies for stress incontinence. Alpha-1 agonists such as pseudoephedrine have been used for SUI, but the side effects of nervousness, dizziness, and insomnia have proved prohibitive.

SUI typically is treated either surgically or with physical therapy designed to strengthen pelvic-floor muscles. Recently, however, advances in the understanding of neuromuscular control of women’s “stress continence control system” has spurred the development of new drugs.²

In this study, duloxetine use was associated with significant decreases in incontinent episodes (as measured by diary entries). Quality-of-life measures also improved significantly. In addition, voiding intervals lengthened, indicating that women were not voiding more frequently to avoid incontinent episodes. This result may indicate duloxetine’s dual efficacy with the continence system: increasing bladder capacity and increasing striated urethral sphincter activity. A more recent analysis of a subgroup of patients with both stress and urge incontinence showed similar improvements.³

Interestingly, cough stress tests at 400 mL and pad tests failed to demonstrate any significant improvement in the study’s treated patients. However, these conflicting results may reflect inherent problems with assessing urinary incontinence treatments: A patient with 400 mL of urine in her bladder may leak with vigorous coughing in the upright position, but if she voids at 300 to 350 mL—a reasonable bladder capacity—she may never leak in “real life.”

Bottom line

Duloxetine hydrochloride appears to be a promising new pharmacologic agent to treat stress incontinence. However, clinicians must keep in mind that even when drugs seem efficacious in clinical trials, they may not yield the same results in clinical practice. Patients in this study completed weeklong diaries every 4 weeks, which, by itself, may improve bladder csontrol.

As mentioned by the authors, larger multinational trials are needed to further demonstrate duloxetine’s safety and efficacy in more diverse clinical settings.

THE QUESTION:
Is duloxetine hydrochloride effective in the treatment of stress urinary incontinence (SUI)?

Past studies

Research has indicated that the neurotransmitters serotonin and norepinephrine are responsible for neural control of the lower urinary tract. Serotogenic agonists generally suppress parasympathetic activity and enhance sympathetic and somatic activity in the lower urinary tract—effects that promote urine storage.

This study

This double-blind, randomized, placebo-controlled study examined 553 women, ages 18 to 65, with at least a 3-month diagnosis of SUI. Subjects were assigned a 12-week course of either placebo (n=138) or duloxetine treatment at 1 of 3 daily doses: 20 mg (n=138), 40 mg (n=137), or 80 mg (n=140). The women were examined once every 4 weeks and asked to keep a diary documenting voiding episodes.

The diary entries revealed a decrease in incontinence episodes for all subjects. Patients taking placebo recorded a 41% decline, compared to 54% in women taking 20 mg/d of duloxetine, 59% for users on 40 mg of duloxetine, and 64% for women taking 80 mg of duloxetine. Among women taking the 80-mg dose, half experienced at least a 64% reduction in incontinence frequency and 67% noted at least a 50% decrease.

Researchers concluded that duloxetine is a safe and effective agent for treating SUI.

Find this study

Norton PA, Zinner NR, Yalcin I, Bump RC. July 2002 issue of American Journal of Obstetrics and Gynecology; abstract online at www3.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

Women suffering from SUI.

Expert commentary

The annual direct cost of female urinary incontinence in the United States is approximately $12.4 billion,¹ with $1.3 billion dedicated to treatment. Of that, surgical management accounts for nearly 80% (or $1 billion), while pharmacologic therapy utilizes only 9% ($114 million).¹ Thus, even with rising medication costs, medical incontinence management uses fewer health-care dollars than surgery. If more women can be effectively treated pharmacologically, therefore, we can conserve valuable health-care resources while reducing related costs, such as time off from work.

If more women can be treated pharmacologically, we can conserve valuable health-care resources.

Presently, there are agents available to treat urge incontinence, but no effective, tolerable medical therapies for stress incontinence. Alpha-1 agonists such as pseudoephedrine have been used for SUI, but the side effects of nervousness, dizziness, and insomnia have proved prohibitive.

SUI typically is treated either surgically or with physical therapy designed to strengthen pelvic-floor muscles. Recently, however, advances in the understanding of neuromuscular control of women’s “stress continence control system” has spurred the development of new drugs.²

In this study, duloxetine use was associated with significant decreases in incontinent episodes (as measured by diary entries). Quality-of-life measures also improved significantly. In addition, voiding intervals lengthened, indicating that women were not voiding more frequently to avoid incontinent episodes. This result may indicate duloxetine’s dual efficacy with the continence system: increasing bladder capacity and increasing striated urethral sphincter activity. A more recent analysis of a subgroup of patients with both stress and urge incontinence showed similar improvements.³

Interestingly, cough stress tests at 400 mL and pad tests failed to demonstrate any significant improvement in the study’s treated patients. However, these conflicting results may reflect inherent problems with assessing urinary incontinence treatments: A patient with 400 mL of urine in her bladder may leak with vigorous coughing in the upright position, but if she voids at 300 to 350 mL—a reasonable bladder capacity—she may never leak in “real life.”

Bottom line

Duloxetine hydrochloride appears to be a promising new pharmacologic agent to treat stress incontinence. However, clinicians must keep in mind that even when drugs seem efficacious in clinical trials, they may not yield the same results in clinical practice. Patients in this study completed weeklong diaries every 4 weeks, which, by itself, may improve bladder csontrol.

As mentioned by the authors, larger multinational trials are needed to further demonstrate duloxetine’s safety and efficacy in more diverse clinical settings.

Objective:

To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink.

Design:

Open, randomized-controlled, 12-month follow-up trial.

Setting:

Health centers for university students and university hospital staff.

Participants:

150 women with urinary tract infection caused by Escherichia coli randomly allocated into 3 groups.

Interventions:

50 mL of cranberry-lingonberry juice concentrate daily for 6 months or 100 mL of lactobacillus drink 5 days a week for 1 year, or no intervention.

Main outcome measure:

First recurrence of symptomatic urinary tract infection, defined as bacterial growth ≥105 colony-forming units/mL in a clean, voided midstream urine specimen.

Results:

The cumulative rate of first recurrence of urinary tract infection during the 12-month follow-up differed significantly between the groups (P=.048). At 6 months, 8 (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had at least 1 recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval, 3% to 36%, P=.023; number needed to treat=5, 95% confidence interval, 3 to 34).

Conclusion:

Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection. (Reprinted with permission from the British Medical Journal.)

Expert commentary:

The American cranberry has long been associated with beneficial effects on urinary tract health. It was once thought that this was due to the highly acidic fruit’s ability to “acidify” the urine, thereby inhibiting bacterial growth. While some early studies supported this mechanism of action, later investigations determined that the quantities of cranberry juice needed to significantly lower urine pH were well beyond normally consumed volumes. In 1959, Bodel et al demonstrated that urine pH was only marginally affected after subjects consumed up to 4 L of cranberry juice cocktail daily.¹

Still, research continued to suggest that drinking cranberry juice could reduce the incidence of bacteriuria and urinary tract infections (UTIs). While the methodology of these clinical trials was suboptimal, the search for how cranberry juice could prevent UTIs continued in the laboratory. A breakthrough occurred in 1984 when Sobota demonstrated that in vitro cranberry juice interfered with the adherence of E. coli to uroepithelial cells.²

Subsequently, a more precise understanding of the cranberry’s mechanism of action has been elucidated. Bacteria, including E. coli, have different types of adhesins on their pili, or fimbriae, allowing the organism to adhere to epithelial cells and proliferate. Cranberries contain compounds called proanthocyanidins (PACs) that inhibit the mannose-resistant (P-fimbriated) adhesins found in strains of E. coli from binding to the uroepithelium.³

Although Kontiokari et al’s recent investigation only included patients with E. coli UTIs, it provides a clinical component to the microbiological and biochemical evidence discovered in the laboratory. Furthermore, while it seems that the addition of lingonberry introduces an unknown variable, the wild plant, known as mountain cranberry, actually is a type of cranberry.

Bottom line:

Patients can decrease their risk of recurrent E. coli UTIs in vivo by consuming cranberry juice. Therefore, physicians should advise their patients to drink 10 to 16 oz of cranberry juice cocktail daily.

Objective:

To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink.

Design:

Open, randomized-controlled, 12-month follow-up trial.

Setting:

Health centers for university students and university hospital staff.

Participants:

150 women with urinary tract infection caused by Escherichia coli randomly allocated into 3 groups.

Interventions:

50 mL of cranberry-lingonberry juice concentrate daily for 6 months or 100 mL of lactobacillus drink 5 days a week for 1 year, or no intervention.

Main outcome measure:

First recurrence of symptomatic urinary tract infection, defined as bacterial growth ≥105 colony-forming units/mL in a clean, voided midstream urine specimen.

Results:

The cumulative rate of first recurrence of urinary tract infection during the 12-month follow-up differed significantly between the groups (P=.048). At 6 months, 8 (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had at least 1 recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval, 3% to 36%, P=.023; number needed to treat=5, 95% confidence interval, 3 to 34).

Conclusion:

Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection. (Reprinted with permission from the British Medical Journal.)

Expert commentary:

The American cranberry has long been associated with beneficial effects on urinary tract health. It was once thought that this was due to the highly acidic fruit’s ability to “acidify” the urine, thereby inhibiting bacterial growth. While some early studies supported this mechanism of action, later investigations determined that the quantities of cranberry juice needed to significantly lower urine pH were well beyond normally consumed volumes. In 1959, Bodel et al demonstrated that urine pH was only marginally affected after subjects consumed up to 4 L of cranberry juice cocktail daily.¹

Still, research continued to suggest that drinking cranberry juice could reduce the incidence of bacteriuria and urinary tract infections (UTIs). While the methodology of these clinical trials was suboptimal, the search for how cranberry juice could prevent UTIs continued in the laboratory. A breakthrough occurred in 1984 when Sobota demonstrated that in vitro cranberry juice interfered with the adherence of E. coli to uroepithelial cells.²

Subsequently, a more precise understanding of the cranberry’s mechanism of action has been elucidated. Bacteria, including E. coli, have different types of adhesins on their pili, or fimbriae, allowing the organism to adhere to epithelial cells and proliferate. Cranberries contain compounds called proanthocyanidins (PACs) that inhibit the mannose-resistant (P-fimbriated) adhesins found in strains of E. coli from binding to the uroepithelium.³

Although Kontiokari et al’s recent investigation only included patients with E. coli UTIs, it provides a clinical component to the microbiological and biochemical evidence discovered in the laboratory. Furthermore, while it seems that the addition of lingonberry introduces an unknown variable, the wild plant, known as mountain cranberry, actually is a type of cranberry.

Bottom line:

Patients can decrease their risk of recurrent E. coli UTIs in vivo by consuming cranberry juice. Therefore, physicians should advise their patients to drink 10 to 16 oz of cranberry juice cocktail daily.

Objective:

To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink.

Design:

Open, randomized-controlled, 12-month follow-up trial.

Setting:

Health centers for university students and university hospital staff.

Participants:

150 women with urinary tract infection caused by Escherichia coli randomly allocated into 3 groups.

Interventions:

50 mL of cranberry-lingonberry juice concentrate daily for 6 months or 100 mL of lactobacillus drink 5 days a week for 1 year, or no intervention.

Main outcome measure:

First recurrence of symptomatic urinary tract infection, defined as bacterial growth ≥105 colony-forming units/mL in a clean, voided midstream urine specimen.

Results:

The cumulative rate of first recurrence of urinary tract infection during the 12-month follow-up differed significantly between the groups (P=.048). At 6 months, 8 (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had at least 1 recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval, 3% to 36%, P=.023; number needed to treat=5, 95% confidence interval, 3 to 34).

Conclusion:

Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection. (Reprinted with permission from the British Medical Journal.)

Expert commentary:

The American cranberry has long been associated with beneficial effects on urinary tract health. It was once thought that this was due to the highly acidic fruit’s ability to “acidify” the urine, thereby inhibiting bacterial growth. While some early studies supported this mechanism of action, later investigations determined that the quantities of cranberry juice needed to significantly lower urine pH were well beyond normally consumed volumes. In 1959, Bodel et al demonstrated that urine pH was only marginally affected after subjects consumed up to 4 L of cranberry juice cocktail daily.¹

Still, research continued to suggest that drinking cranberry juice could reduce the incidence of bacteriuria and urinary tract infections (UTIs). While the methodology of these clinical trials was suboptimal, the search for how cranberry juice could prevent UTIs continued in the laboratory. A breakthrough occurred in 1984 when Sobota demonstrated that in vitro cranberry juice interfered with the adherence of E. coli to uroepithelial cells.²

Subsequently, a more precise understanding of the cranberry’s mechanism of action has been elucidated. Bacteria, including E. coli, have different types of adhesins on their pili, or fimbriae, allowing the organism to adhere to epithelial cells and proliferate. Cranberries contain compounds called proanthocyanidins (PACs) that inhibit the mannose-resistant (P-fimbriated) adhesins found in strains of E. coli from binding to the uroepithelium.³

Although Kontiokari et al’s recent investigation only included patients with E. coli UTIs, it provides a clinical component to the microbiological and biochemical evidence discovered in the laboratory. Furthermore, while it seems that the addition of lingonberry introduces an unknown variable, the wild plant, known as mountain cranberry, actually is a type of cranberry.

Bottom line:

Patients can decrease their risk of recurrent E. coli UTIs in vivo by consuming cranberry juice. Therefore, physicians should advise their patients to drink 10 to 16 oz of cranberry juice cocktail daily.