A systematic review and meta-analysis compared anticolinergics to placebo and other medications «Farag F, Sakalis VI, Arteaga SM, et al. What Are t...»1. Anticholinergics decreased urge incontinence episodes for -0.48 episodes per day (-0.71 to –0.24) compared to placebo, translating to about -32 % decrease in incontinence episodes.
Similarly, in a systematic review and meta-analysis of 7 RCT:s «Ananda IGYP, Surya RNH, Surya PA, et al. Efficacy ...»2 comparing solifenacin to placebo, anticholinergics decreased daily urinary incontinence episodes by 0.56 episodes per day (−0.80 to −0.32). A network meta-analysis on anticholinergics for urinary incontinence suggested similar impact from different anticholinergics with decrease in leakage episodes ranging between -0.32 and -0.58 «Herbison P, McKenzie JE. Which anticholinergic is ...»3.
A Cochrane review found 4 points improvement in health-related quality of life (scale 0-100), suggesting little to no improvement «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4. However, the evidence was low quality due to high risk of bias (insufficient reporting and publication bias).
The Cochrane review found dry mouth is more common with anticholinergics compared to placebo, occurring in 23.9% vs. 6.3% of patients (RD 16%). Urinary retention occurred in 0.3% of patients using placebo, compared to 0.7-2.1% of patients on anticholinergics (RD 0.9 %)), and constipation in 6.3% vs. 3.3% of patients (RD 3.4 %).
The level of evidence was downgraded once.
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis | |||||
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Farag F, Sakalis VI, Arteaga SM, et al. What Are t...»1 | SR/MA | Women 18 yr with OAB symptoms as defined by trialists |
Antimuscarinics versus placebo | Change in the number of urgency incontinence episodes OAB-q (quality of life TAEs |
Moderate |
| «Ananda IGYP, Surya RNH, Surya PA, et al. Efficacy ...»2 | SR/MA | Adult male and female OAB | Solifenacin vs. placebo | Change in urge and incontinence episodes, change in micturition frequency, change in nocturia episodes, change in urine volume, adverse events | Moderate |
| «Herbison P, McKenzie JE. Which anticholinergic is ...»3 | Network MA | Men and women with OAB | Tolterodine, oxybutynin,trospium, propiverine, solifenacin, darifenacin, imidafenacin, and fesoterodine vs placebo | The number of leakage episodes; the number of voids per day;cure or improvement; and dry mouth | Moderate |
| «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4 | SR/MA | Women with overactive bladder syndrome | Monotherapy of darifenacin /fesoterodine/ imidafenacin/ oxybutynin/ propantheline/ propiverine/ solifenacin/ tolterodine/trospium OR placebo | Condition-specific quality of life, patient perception of cure or improvement, mean number of urgency episodes per 24 hours, TAEs | High |
| Reference | Comments |
|---|---|
| «Farag F, Sakalis VI, Arteaga SM, et al. What Are t...»1 | 104 studies. In total across the rest of the studies, 29,682 people were given an
anticholinergic drug compared to 17,424 people who were given a placebo. One study
investigated symptoms only in men, while nine looked at symptoms in women. The rest
of the studies included both men and women. None of the included studies reported results for those with frequency and/or urgency alone (OAB-dry) separately to those with urgency urinary incontinence (OAB-wet). As such, it was not possible to assess by type of overactive bladder. Health-related quality of life was measured with 0-100 scales: King's Health Questionnaire, Incontinence Quality of Life, and Overactive Bladder Questionnaire. Risk of bias (according to Cochrane): high (mostly due to insufficient reporting) |
| «Ananda IGYP, Surya RNH, Surya PA, et al. Efficacy ...»2 | 8 RCTs. 4387 participants: 2390 patients allocated to the solifenacin group, 1997
to the placebo group. Inclusion criteria: studies involving only adult patients, with RCTs as the preferred study design, and articles written in English, focusing on the primary outcomes of interest related to OAB symptoms, including urgency, incontinence, and micturition frequency. Exclusion criteria: studies with a pediatric population and articles not written in English. Risk of bias: low. Some missing data. |
| «Herbison P, McKenzie JE. Which anticholinergic is ...»3 | 128 RCTs with 58 335 participants. Inclusion criteria: To be included a study had to be a parallel randomized trialcomparing an anticholinergic drug with placebo or anotheranticholinergic drug. The included anticholinergic drugs weretolterodine, oxybutynin, trospium, propiverine, solifenacin,darifenacin, imidafenacin, and fesoterodine. Participants had to be adults with overactive bladders. Pairwise comparisons of all treatments that were compared directly were carried out using random effects meta-analysis. All drugs, apart from oxybutynin ER and trospium, were more effective than placebo, and there were no statistically significant differences between the different drugs (in incontinence episodes), data available from 65 studies. |
| «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4 | 45 RCTs. Exclusion criteria: past medical history of pelvic radiotherapy for pelvic organ malignancy, active urinary tract infection, urinary tract cancer, neuropathic bladder dysfunction, urinary tract stones; studies predominantly on women with mixed urinary incontinence, chronic interstitial cystitis/bladder pain syndrome. Risk of bias: moderate. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (sd) I | Mean (sd) C | Mean difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations. I=intervention; C=comparison; CI=confidence interval *not calculated by the study authors |
|||||
| «Farag F, Sakalis VI, Arteaga SM, et al. What Are t...»1 | 6 RCTs, n = 4688 | 6-12 weeks | 1.49* | -0.48 (-0.71 to -0.24) relative effect: -32% (-16% to -48%) |
|
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate
The quality of evidence is downgraded due to study limitations. |
|||||
| «Ananda IGYP, Surya RNH, Surya PA, et al. Efficacy ...»2 | 7 (2239/1937) | (MD = -0.56, 95% CI: -0.80 to -0.32) |
|||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: very low The quality of evidence is downgraded due to study limitations, imprecision. |
|||||
| «Ananda IGYP, Surya RNH, Surya PA, et al. Efficacy ...»2 | 3 RCTs, n= 238 | No significant differences were found between antimuscarinics and beta-3 | |||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: low The quality of evidence is downgraded due to study limitations (mostly due to insufficient reporting) and imprecision. The meta-analysis used fixed-effects model, which may result in too precise estimates. |
|||||
| «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4 | 12 RCTs, n= 6804 | MD -4.41 (-5.28 to -3.54) | |||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations. |
|||||
| «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4 | 66 studies, I 24 523, C 13 845 | 5859 (23,9 %) | 875 (6,3 %) | RR 3.50 (3.26 to 3.75) RD 16 % |
|
| «Ananda IGYP, Surya RNH, Surya PA, et al. Efficacy ...»2 | 11 179 | not reported | RR 3.20, (1.54 to 6.67) | ||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations. |
|||||
| «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4 | I 4614, C 3248 | 73 (1.6 %) | 11 (0.3 %) | RR 3.52 (2.04 to 6.08) RD 0.9 % |
|
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations. |
|||||
| «Stoniute A, Madhuvrata P, Still M, et al. Oral ant...»4 | 24756/12561 | 1557 (6.3%) | 410 (3.3%) | RR 2.03 (1.78 to 2.31) | |