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Anticholinergic drugs for overactive bladder symptoms in adults


Around 16% to 45% of adults have overactive bladder symptoms, urgency with frequency or urgency urinary incontinence, or both, termed overactive bladder syndrome. Anticholinergic drugs are common treatments.

The objective of the study was to compare the effects of different anticholinergic drugs for overactive bladder symptoms.

Eighty-six trials, 70 parallel and 16 cross-over design, were included ( involving 31,249 adults ) in the analysis. Most trials were described as double-blind but were variable in other aspects of quality. Cross-over studies did not present data in a way that could be included in the meta-analyse. Twenty-nine collected quality of life data ( the primary outcome measure ) using validated measures, but only 15 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 10 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 or 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 dry mouth rates ( RR=0.69, 95% CI 0.51 to 0.94 ) were 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 or 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.
Those taking Fesoterodine had a 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 doses ( 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 a greater risk of dry mouth with the 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 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 at eight to 12 weeks.

Extended versus immediate release preparations of Oxybutynin or Tolterodine, or both: there were no statistically significant differences for cure or 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 a skin reaction at the transdermal patch site at 12 weeks.

According to authors, 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, which 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 a 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 outcomes in these studies.
There were insufficient data from trials of other anticholinergic drugs to draw any conclusions. ( Xagena )

Madhuvrata P et al, Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD005429

XagenaMedicine_2012



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