-
The Cochrane Database of Systematic... May 2023Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic... (Review)
Review
BACKGROUND
Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006.
OBJECTIVES
To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults.
SEARCH METHODS
We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated.
SELECTION CRITERIA
We included randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies. The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition-specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range -100 to 0); 12 studies, 6804 participants; low-certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate-certainty evidence), and the mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate-certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low-certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low-certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low-certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24-hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops.
Topics: Adult; Humans; Cholinergic Antagonists; Quality of Life; Tolterodine Tartrate; Urinary Bladder, Overactive; Systematic Reviews as Topic; Drug-Related Side Effects and Adverse Reactions
PubMed: 37160401
DOI: 10.1002/14651858.CD003781.pub3 -
PloS One 2024We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparison of the efficacy and complications of tolterodine and α-adrenergic receptor blockers in improving ureteral stent-related symptoms: A systematic review and meta-analysis.
OBJECTIVE
We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral stent-related symptoms.
METHODS
Until August 2023, we conducted a comprehensive literature search on PubMed, Embase, Web of Science, and Cochrane Library to identify randomized controlled trials evaluating the efficacy and complications of tolterodine and α-adrenergic receptor blockers in treating ureteral stent-related symptoms. Two reviewers independently screened studies and extracted data. The scores from various domains of the Ureteral Stent Symptom Questionnaire (USSQ) were summarized and compared, and statistical analysis was performed using RevMan 5.4.0 software.
RESULTS
A total of 8 studies met the inclusion criteria for our analysis. These studies were conducted at different centers. All studies were randomized controlled trials, involving a total of 487 patients, with 244 patients receiving α-adrenergic receptor blockers and 243 patients receiving tolterodine. The results showed that tolterodine demonstrated significantly better improvement in body pain (MD, 1.56; 95% CI [0.46, 2.66]; p = 0.005) (MD, 0.46; 95% CI [0.12, 0.80]; p = 0.008) (MD, 3.21; 95% CI [1.89, 4.52]; p = 0.00001) among patients after ureteral stent placement compared to α-adrenergic receptor blockers at different time points. Additionally, at 4 weeks, tolterodine showed superior improvement in general health (MD, 0.15; 95% CI [0.03, 0.27]; p = 0.01) and urinary symptoms (MD, 1.62; 95% CI [0.59, 2.66]; p = 0.002) compared to α-adrenergic receptor blockers, while at 6 weeks, tolterodine showed better improvement in work performance (MD, -1.60; 95% CI [-2.73, -0.48]; p = 0.005) compared to α-adrenergic receptor blockers. Additionally, the incidence of dry mouth (RR, 4.21; 95% CI [1.38, 12.87]; p = 0.01) is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, there were no significant statistical differences between the two drugs in other outcomes.
CONCLUSION
This meta-analysis suggests that tolterodine is superior to α-adrenergic receptor blockers in improving physical pain symptoms after ureteral stent placement, while α-adrenergic receptor blockers are more effective than tolterodine in enhancing work performance. Additionally, the incidence of dry mouth is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, higher-quality randomized controlled trials are needed to further investigate this issue.
Topics: Tolterodine Tartrate; Humans; Stents; Adrenergic alpha-Antagonists; Ureter; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38701097
DOI: 10.1371/journal.pone.0302716 -
BMC Urology Oct 2014Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies... (Review)
Review
BACKGROUND
Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS.
METHODS
A wide Medline search was performed including the combination of following words: "LUTS", "BPH", "OAB", "antimuscarinic", "tolterodine", "tolterodine ER". IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER.
RESULTS
Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment.
CONCLUSION
Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.
Topics: Adrenergic alpha-Antagonists; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Xerostomia
PubMed: 25348235
DOI: 10.1186/1471-2490-14-84 -
Acta Pharmaceutica (Zagreb, Croatia) Sep 2017The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were...
The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10-0.15 mm), tensile strength (4.62-9.98 MPa) and modulus of elasticity (20-29 MPa). There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB.
Topics: Administration, Cutaneous; Animals; Male; Rats, Sprague-Dawley; Skin Absorption; Tolterodine Tartrate; Transdermal Patch; Urinary Bladder, Overactive
PubMed: 28858835
DOI: 10.1515/acph-2017-0027 -
International Braz J Urol : Official... 2021Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to... (Randomized Controlled Trial)
Randomized Controlled Trial
A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial.
INTRODUCTION
Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace.
OBJECTIVES
In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin.
PATIENTS AND METHODS
This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics.
RESULTS
The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone.
CONCLUSION
Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.
Topics: Adolescent; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Solifenacin Succinate; Tolterodine Tartrate
PubMed: 32840337
DOI: 10.1590/S1677-5538.IBJU.2019.0448 -
International Braz J Urol : Official... 2023bladder based on a systematic review and network meta-analysis approach. (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
bladder based on a systematic review and network meta-analysis approach.
METHODS
Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software.
RESULT
A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache.
CONCLUSION
Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.
Topics: Humans; Urinary Bladder, Overactive; Solifenacin Succinate; Tolterodine Tartrate; Network Meta-Analysis; Double-Blind Method; Constipation; Xerostomia; Treatment Outcome; Muscarinic Antagonists; Randomized Controlled Trials as Topic
PubMed: 37506033
DOI: 10.1590/S1677-5538.IBJU.2023.0158 -
Clinical Interventions in Aging 2009After lifestyle and behavioral measures to control overactive bladder, the mainstay of pharmacological treatment is the use of antimuscarinic therapy. Overactive bladder... (Review)
Review
After lifestyle and behavioral measures to control overactive bladder, the mainstay of pharmacological treatment is the use of antimuscarinic therapy. Overactive bladder predominantly affects older people, who experience the most severe disease, and are also at a greater risk of side effects from antimuscarinic therapy. Thus it is imperative that data are available on the efficacy and tolerability of this group of drugs when used in older people. This article reviews the pathophysiology of the condition, its effect on the elderly and the evidence for the use of extended release tolterodine in the elderly using data from placebo and active drug controlled studies.
Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive
PubMed: 19503781
DOI: 10.2147/cia.s4233 -
Drug Metabolism and Pharmacokinetics Jun 2011Tolterodine is known as a drug which exhibits ethnic differences in pharmacokinetics between Japanese and Koreans despite genetic similarities among the populations of...
Tolterodine is known as a drug which exhibits ethnic differences in pharmacokinetics between Japanese and Koreans despite genetic similarities among the populations of East Asian countries. Tolterodine is mainly metabolized by CYP2D6 to a 5-hydroxymethyl metabolite (5-HM), and 5-HM is also metabolized by CYP2D6. The reduced-function allele CYP2D6*10 is frequently observed in Asian populations. We investigated differences in the pharmacokinetics of tolterodine between small Japanese and Korean study populations by physiological and stochastic approaches with consideration of the CYP2D6 genotype. The genotype frequencies of CYP2D6*10/*10 and CYP2D6*5/*10 were found to be higher in Koreans than in Japanese, which suggested that this frequency difference occurred incidentally. The effects of CYP2D6 genotype and ethnicity on the intrinsic clearance of tolterodine by CYP2D6 were tested and only genotype was found to be a significant factor by ANCOVA. A simulation was conducted to confirm whether the observed differences in tolterodine exposure could be explained by the differences in genotype frequency found in this study. It was confirmed that the variability of intrinsic clearance could be responsible for the incidental exposure differences. In conclusion, apparent differences in exposure were found between small Japanese and Korean study populations because of the variability of intrinsic clearances and genotype frequencies.
Topics: Adult; Area Under Curve; Asian People; Benzhydryl Compounds; Computer Simulation; Cresols; Cytochrome P-450 CYP2D6; Ethnicity; Female; Gene Frequency; Genotype; Humans; Japan; Korea; Male; Models, Biological; Phenylpropanolamine; Polymorphism, Genetic; Tolterodine Tartrate; Young Adult
PubMed: 21273733
DOI: 10.2133/dmpk.DMPK-10-RG-112 -
Frontiers in Neuroscience 2023This study aimed to retrospectively compare the efficacy and safety of micro-radiofrequency (RF) therapy through the urethra vs. oral tolterodine tartrate in the...
PURPOSE
This study aimed to retrospectively compare the efficacy and safety of micro-radiofrequency (RF) therapy through the urethra vs. oral tolterodine tartrate in the treatment of newly diagnosed overactive bladder (OAB).
MATERIALS AND METHODS
In this study, 46 patients who were newly diagnosed with moderate-to-severe OAB were included; 23 of them underwent the micro-RF treatment procedure, and the other 23 patients took tolterodine. Bladder diaries were recorded 3 days before treatment and during the follow-up period on 1, 3, and 7 weeks after micro-RF therapy or oral tolterodine. Micturition parameters including daily voiding times, daily urge urinary incontinence (UI) episodes, daily urgency episodes, mean volume per micturition, post-void residual volume (PVR), maximum urine flow rate (Qmax), overactive bladder symptom score (OABSS), and quality of life (QoL) score were analyzed.
RESULTS
All 46 patients underwent either micro-RF or oral tolterodine treatment, as well as a complete follow-up. The incidence of adverse events in the micro-RF group was 8.7% (2/23), and that in the tolterodine group was 43.5% (10/23). The following two adverse events happened in the micro-RF group: an injury to the urethra during catheterization in a man and a urinary tract infection in a woman, both of which were relieved or disappeared after day 3. The adverse effects in the tolterodine group were mainly dry mouth (4/23), dysuria (5/23), and constipation (8/23), but none of the patients withdrew from the drug therapy. Compared to pre-therapy, all parameters of both groups, including daily voiding times, daily urgency episodes, mean volume per micturition, OABSS, and QoL score, demonstrated significant improvements during follow-up in 7 weeks after therapy, except for daily UI episodes in the tolterodine group, while the above parameters showed bigger improvements in the micro-RF group than in the tolterodine group. Besides, the general treatment efficacy of micro-RF was 73.9% (17/23), which was significantly better than tolterodine (10/23, 43.5%), and the difference was 30.4% [95% CI: 3.4-57.5%, = 0.036].
CONCLUSION
In this retrospective study, we found that micro-RF therapy is safe and more effective than oral tolterodine for newly diagnosed moderate-to-severe OAB in a short-term follow-up. Stronger evidence would be provided through a well-designed, prospective, randomized controlled trial.
PubMed: 37021128
DOI: 10.3389/fnins.2023.1120843