Anticholinergic and other Drugs for Overactive Bladder Symptoms in Adults

A Cochrane review [Abstract] 1 included 86 studies (70 parallel, 16 cross-over designs) with a total of 31 249 subjects.

Oxybutynin versus tolterodine:

• There were no statistically significant differences for patient perceived improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events (RR 0.52, 95% CI 0.40 to 0.66; 8 trials, n=2686), and less risk of dry mouth (RR 0.65, 95% CI 0.60 to 0.71; 10 trials, n=3140), with tolterodine.

Solifenacin versus tolterodine:

• There were statistically significant differences for quality of life (QoL) (standardised mean difference (SMD) -0.12, 95% CI -0.23 to -0.01; 3 trials, n=1293), patient reported cure or improvement (RR 1.25, 95% CI 1.13 to 1.39; 2 trials, n=1252), leakage episodes in 24 hours (WMD -0.30, 95% CI -0.53 to -0.08; 4 trials, n=1300) and urgency episodes in 24 hours (WMD -0.43, 95% CI -0.74 to -0.13; 4 trials, n=1979), all favouring solifenacin. There was no difference in withdrawals due to adverse events and dry mouth.

Fesoterodine versus extended release tolterodine:

• In 3 trials, there were statistically significant differences for quality of life (SMD -0.20, 95% CI -0.27 to -0.14; n=3492), patient reported cure or improvement (RR 1.11, 95% CI 1.06 to 1.16; n=3691 ), leakage episodes (WMD -0.19, 95% CI -0.30 to -0.09; n=3525), and urgency episodes (WMD -0.44, 95% CI -0.72 to -0.16; n=3666) in 24 hours, all favouring fesoterodine. Those taking fesoterodine had a higher risk of withdrawal due to adverse events (RR 1.45, 95% CI 1.07 to 1.98; n=3876) and higher risk of dry mouth (RR 1.80, 95% CI 1.58 to 2.05 n=3858).

Different doses tolterodine:

• The usual recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effect of 1 mg, 2 mg and 4 mg doses was similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses.

Different doses of solifenacin:

• The standard recommended starting dose of 5 mg once daily was compared to 10 mg. While frequency and urgency were less (better) with 10 mg compared to 5 mg, there was a higher risk of dry mouth with 10 mg solifenacin.

Different doses of fesoterodine:

• The recommended starting dose of 4 mg once daily was compared to 8 mg and 12 mg. The clinical efficacy (patient reported cure, leakage episodes, micturition per 24 hours) of 8 mg was better than 4 mg fesoterodine but with a higher risk of dry mouth with the 8 mg dose.There was no statistically significant difference between 4 mg and 12 mg in efficacy but the dry mouth was significantly higher with 12 mg

Extended versus immediate release preparations of oxybutynin and/or tolterodine:

• There were no statistically significant differences for cure/improvement, leakage episodes or micturitions in 24 hours, or withdrawals due to adverse events, but there were few data. Overall, extended release preparations had less risk of dry mouth.

One extended release preparation versus another:

• There was less risk of dry mouth with oral extended release tolterodine than oxybutynin (RR 0.75, 95% CI 0.59 to 0.95), but no difference between transdermal oxybutynin and oral extended release tolterodine although some people withdrew due to skin reaction at the trandermal patch site.

There is little or no evidence available about quality of life, costs, or long-term outcome. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

Another Cochrane review 2 (abstract , review [Abstract]) included 12 studies with a total of 690 participants. There were seven crossover trials and five parallel group studies. For the comparisons between anticholinergic drugs with tricyclic antidepressants, alpha adrenergic agonists, afferent nerve inhibitors, and calcium channel blocker a single trial was identified for each. No studies were identified comparing botulinum toxin with anticholinergics. Nine trials compared flavoxate with anticholinergics. There was no evidence of a difference in cure rates between anticholinergics and flavoxate. Adverse effects were more frequent in anticholinergic groups versus flavoxate groups (RR 2.28 95% CI 1.45 to 3.56). There was no strong evidence to favour either anticholinergic drugs or the comparators.

References

• Madhuvrata P, Cody JD, Ellis G et al. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev 2012;(1):CD005429.[PubMed]
• Roxburgh C, Cook J, Dublin N. Anticholinergic drugs versus other medications for overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2007;(4):CD003190.