Drug therapy for incontinence: New agents, new applications
Profiles and practice recommendations for 3 new drugs for urinary incontinence, plus new potential for an “old” medication
IN THIS ARTICLE
- A simple questionnaire to differentiate urge and stress incontinence
Duloxetine may avert surgery. Taken together, these studies indicate that duloxetine is effective and may improve incontinence enough to render surgery unnecessary.
INTEGRATING EVIDENCE AND EXPERIENCE
Zinner N, Gittleman M, Harris R, et al. Trospium chloride improves overactive bladder symptoms: a multicenter phase III trial. J Urol. 2004;171:2311–2315
What goes into a drug approval? In weighing the merits of trospium chloride (Sanctura), one of the studies the US Food and Drug Administration considered was a 12-week multicenter, double-blind, parallel, placebo-controlled trial that compared 20 mg of the drug (twice daily) with placebo.
Trospium significantly reduced the frequency of toilet voids and urge incontinence episodes, compared with placebo. It also increased the average volume per void and decreased urge severity and daytime frequency.
However, several factors limited this study’s application to “real-life” women with overactive bladder.
1. Most participants were older white women
A total of 523 patients were enrolled, more than 70% of them women. The mean age was over 60 years, and about 80% of participants were white. More than half had already used a drug for overactive bladder.
2. Brief duration did not reflect real life
Most patients with overactive bladder need treatment for much longer than 12 weeks, so this study does not address the long-term efficacy or tolerability of trospium chloride.
3. Placebo response was substantial
Patients in the placebo arm had less frequent urination, decreased nocturia, fewer episodes of urge incontinence in 24 hours, and reduced urgency with voiding. Although these outcomes were statistically significant in the treatment group, were they clinically meaningful?
A difference of 2 tablespoons. The mean increase in average voided volume in the trospium group was 32.1 mL, compared with an increase of 7.7 mL in the placebo group. Although the P value was outstanding (P≤0.0001), one could argue that an increase in bladder capacity of less than 2 tablespoons is clinically meaningless.
Try non-drug measures first
In this study, 54% of patients taking placebo reduced the number of incontinence episodes in 24 hours, compared with 71% on the active drug. In addition, 10% of patients taking placebo became completely dry, compared with 21% on the active drug.
Because the placebo effect in these studies is always strong, focused behavioral therapy (“bladder drill” or bladder retraining) should be the first line of treatment for overactive bladder, reserving drugs for those in whom behavioral treatment is not effective, or as an initial “crutch” to help advance the behavioral program, weaning patients off medications whenever possible.
