Which anticholinergic drug for overactive bladder symptoms in adults.

Author(s): Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith EJ.

Affiliation(s): Obstetrics & Gynaecology, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.Priyamadhuvrata@nhs.net

Publication date & source: 2012, Cochrane Database Syst Rev. , 1:CD005429

BACKGROUND: Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments. OBJECTIVES: To compare the effects of different anticholinergic drugs for overactive bladder symptoms. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 March 2011) and reference lists of relevant articles. SELECTION CRITERIA: Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook. MAIN RESULTS: Eighty six trials, 70 parallel and 16 cross-over designs were included (31,249 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analyses. Twenty nine collected quality of life data (the primary outcome measure) using validated measures, but only fifteen reported useable data.Tolterodine versus oxybutynin: There were no statistically significant differences for quality of life, patient reported cure or improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events with tolterodine (Risk Ratio (RR) 0.52, 95% confidence interval (CI) 0.40 to 0.66, data from eight trials), and less risk of dry mouth (RR 0.65, 95% CI 0.60 to 0.71, data from ten trials).Solifenacin versus tolterodine: There were statistically significant differences for quality of life (standardised mean difference (SMD) -0.12, 95% CI -0.23 to -0.01, data from three trials), patient reported cure/improvement (RR 1.25, 95% CI 1.13 to 1.39, data from two trials), leakage episodes in 24 hours (weighted mean difference (WMD) -0.30, 95% CI -0.53 to -0.08, data from four studies) and urgency episodes in 24 hours (WMD -0.43, 95% CI -0.74 to -0.13, data from four trials), all favouring solifenacin. There was no difference in withdrawals due to adverse events and dry mouth, but after sensitivity analysis the dry mouth (RR 0.69, 95% CI 0.51 to 0.94) was statistically significantly lower with solifenacin when compared to Immediate Release (IR) tolterodine.Fesoterodine versus extended release tolterodine: Three trials contributed to the meta analyses. There were statistically significant differences for quality of life (SMD -0.20, 95% CI -0.27 to -0.14), patient reported cure/improvement (RR 1.11, 95% CI 1.06 to 1.16), leakage episodes (WMD -0.19, 95% CI -0.30 to -0.09), frequency (WMD -0.27, 95% CI -0.47 to -0.06) and urgency episodes (WMD -0.44, 95% CI -0.72 to -0.16) in 24 hours, all favouring fesoterodine, but those taking fesoterodine had higher risk of withdrawal due to adverse events (RR 1.45, 95% CI 1.07 to 1.98) and higher risk of dry mouth (RR 1.80, 95% CI 1.58 to 2.05) at 12 weeks.Different doses of tolterodine: The standard 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 effects of 1 mg, 2 mg and 4 mg doses were similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses at two to 12 weeks.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 at four to 12 weeks.Different doses of fesoterodine:The recommended starting dose of 4mg once daily was compared to 8 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 8 mg.There was no statistically significant difference between 4 and 12 mg in the efficacy but the dry mouth was significantly higher with 12 mg at eight to 12 weeks.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 at two to 12 weeks.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 transdermal patch site at 12 weeks. AUTHORS' CONCLUSIONS: Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective, with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth.Between solifenacin and immediate release tolterodine, solifenacin might be preferred for better efficacy and less risk of dry mouth. Solifenacin 5 mg once daily is the usual starting dose, this could be increased to 10 mg once daily for better efficacy but with increased risk of dry mouth.Between fesoterodine and extended release tolterodine, fesoterodine might be preferred for superior efficacy but has higher risk of withdrawal due to adverse events and higher risk of dry mouth.There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.