Anticholinergic drugs are recommended as second-line treatment for women with urgency urinary incontinence who do not get enough relief from pelvic floor muscle training or mirabegron.
The recommendation is strong because of large effect size for patient important outcomes. Anticholinergics are only recommended as second-line treatment because of uncertainty in the balance of benefits and harms related to anticholinergic effects.
A Cochrane review [Abstract] 1 included 104 trials with over 47 000 subjects. Nine medications were tested: darifenacin, oxybutynin, propiverine, propantheline, tolterodine, trospium chloride, solifenacin, fesoterodine, and imidafenacin.
At the end of the treatment period, cure or improvement (relative risk [RR] 1.38, 95% CI 1.15 to 1.66; 9 studies, n=8 457), mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, n=16 875) and difference in number of voids in 24 hours (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, n=19 395) were statistically significant favouring medication. Statistically significant but modest sized improvements in quality of life scores were reported in recently completed trials. There was three times the rate of dry mouth in the medication group (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, n=38 368) and more withdrawals due adverse effects (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, n=36 943). Sensitivity analysis, while limited by small numbers of trials, showed little likelihood that these effects were modified by age, sex, diagnosis, or choice of drug.
A systematic review and network meta-analysis 4 of treatments for urinary incontinence in women included 84 studies (32 in stress UI, 16 in urgency UI, 4 in mixed UI, and 32 in any or unspecified UI type). For urge UI, both behavioral therapy and anticholinergics wee more effective than no treatment (behavioral therapy OR 3.06, CI 2.16 to 4.35; anticholinergics OR 1.95, CI 1.32 to 2.88). Indirect evidence indicated that combination therapy was more effective than no treatment (OR 2.28, CI 1.18 to 4.39), with similar but statistically nonsignificant findings across all studies. Behavioral therapy was statistically significantly more effective than anticholinergics in achieving cure or improvement (OR 1.57, CI 1.02 to 2.43).
Another Cochrane review 2 (abstract , review [Abstract]) included 23 trials involving a total of 3 685 participants. The duration of follow up varied from two to 52 weeks. During 3 to 12 weeks of treatment, symptomatic improvement was more common amongst those on anticholinergic drugs compared with bladder training (RR 0.74; 95% CI 0.61 to 0.91; 7 small trials). The data favoured combination of anticholinergics with bladder training compared with bladder training alone (RR 0.57; 95% Cl 0.38 to 0.88; 3 small trials) or anticholinergics alone (RR for improvement 0.80; 95% CI 0.62 to 1.04; 3 small trials). Adverse effects, such as dry mouth, were reported by around a third of those taking anticholinergics.
A meta-analysis 3 included 53 trials comparing solifenacin 5 mg/day with other antimuscarinic agents. Solifenacin 5mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision or constipation.
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