Efficacy and safety of propiverine in SCI-patients suffering from detrusor hyperreflexia--a double-blind, placebo-controlled clinical trial. Emepronium carrageenate: clinical effects and urinary excretion in treatment of female urge incontinence. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Tolterodine reduces the number of urge incontinence episodes in patients with an overactive bladder. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Placebo--the drug of choice in female motor urge incontinence? Efficacy of antimuscarinic therapy for overactive bladder with varying degrees of incontinence severity. Efficacy and cardiac safety of propiverine in elderly patients - a double-blind, placebo-controlled clinical study. Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study. Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder. Urinary urge incontinence: randomised crossover trials of penthienate versus placebo and propantheline. Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens. Efficacy and safety of two doses of tolterodine versus placebo in patients with detrusor overactivity and symptoms of frequency, urge incontinence, and urgency: urodynamic evaluation. The International Study Group. Dose titration in clinical trials. An example using emepronium carrageenate in detrusor instability. Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study. [Assessment of effectiveness of and tolerance to oxybutynin in the treatment of unstable bladder in women]. The urodynamic and subjective results of treatment of detrusor instability with oxybutynin chloride. Urinary incontinence in old age. A controlled clinical trial of emepronium bromide. Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial. Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Oxybutynin chloride for geriatric urinary dysfunction: a double-blind placebo-controlled study. Urodynamic changes associated with behavioral and drug treatment of urge incontinence in older women. Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients. Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial. Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine. Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. Trospium chloride improves overactive bladder symptoms: a multicenter phase III trial. Effect of trospium chloride on urodynamic parameters in patients with detrusor hyperreflexia due to spinal cord injuries. A multicentre placebo-controlled double-blind trial. Tolterodine: a safe and effective treatment for older patients with overactive bladder. Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. Health-related quality of life of Japanese patients with overactive bladder treated with extended-release tolterodine or immediate-release oxybutynin: a randomized, placebo-controlled trial. Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability. Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. The treatment of detrusor instability in post-menopausal women with oxybutynin chloride: a double blind placebo controlled study. Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity. Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial. Oxybutynin chloride in the treatment of female idiopathic bladder instability. Results from double blind treatment. Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo.
The aim of this double-blind, randomised, prospective, multicentre trial was to evaluate the efficacy of propiverine in patients suffering from detrusor hyperreflexia caused by spinal cord injury in comparison to placebo.
                The treatment period of 14 days comprised visits at baseline (V1) and after 14 days treatment (V2). Fifteen mg propiverine t.i.d. or placebo t.i.d. were administered as medication. The following efficacy parameters were adopted: the urodynamic parameters maximal cystometric bladder capacity, bladder volume on onset of the first as well as duration and amplitude of the maximum detrusor contraction, bladder compliance and residual urine, and subjective assessment of efficacy by physicians. For the evaluation of the safety of propiverine the incidence rate of adverse events by directly questioning as well as laboratory parameters were investigated. For biometrical evaluation t-test for independent groups was applied.
                One hundred and thirteen patients were investigated. The maximal cystometric bladder capacity increased significantly in the propiverine group, on average by 104 ml (V1: 262+/-132 ml. V2: 366+/-143 ml, P<0.001). The changes in bladder capacity during the first contraction and the maximum detrusor contraction in the verum group were both statistically significant. The bladder compliance documented a more pronounced increase under propiverine in comparison to placebo. Residual urine increased by 37+/-71 ml in the propiverine group, significantly more than in the placebo group (P=0.01). Sixty-three per cent of the patients expressed subjectively an improvement under propiverine in comparison with 23% of the placebo group. Expected anticholinergic adverse events occurred: dryness of the mouth (37% in the verum and 8% in the placebo group), accommodation disorders (28% and 2% respectively). Nausea, constipation, headache, dizziness, tiredness and palpitations were reported in almost comparable incidence rates between 3 and 13% in both treatment groups. Eight drop-outs were registered in the propiverine group (five due to adverse events) and three in the placebo group (one due to adverse events). The laboratory parameters revealed no changes.
                Propiverine proved its efficacy in detrusor hyperreflexia with regard to the urodynamic parameters of the maximal cystometric bladder capacity and detrusor contractility. Anticholinergic adverse events such as dryness of the mouth and accommodation disorders were considered being tolerable. The increase in residual urine reflects the therapeutically desired effect of detrusor relaxation because the majority of patients normally practise intermittent catheterisation for bladder emptying. Eighteen women (median age 54 years, 36-79) with urinary motor urge (n = 13) or sensory urge (n = 5) incontinence were treated for three 2-week periods with emepronium carrageenate (EC) (Cetiprin Novum) in daily doses of 500 and 1000 mg and placebo. Subjectively the women experienced an increased ability to control micturition, i.e. less urge, during EC treatment. Only mild and mainly anticholinergic side effects were recorded, most frequently dryness of the mouth. As regards side effects, the evaluation of objective effects were complicated by a tendency towards carry-over effect to placebo. Placebo in the first treatment periods were analysed solely; no effects of placebo could be demonstrated. Compared with the reference period, decreases in the total number of micturitions (approx. 20%) and in the number of urge incontinence episodes (approx. 75%) were seen. As compared with placebo, a significant increase (approx. 25%) in the average micturition volume could be demonstrated. The percentage urinary excretion of emepronium decreased with increasing oral intake and with advancing age. Probably, an initial daily dosage of 500 mg EC will do well in younger women (less than 50 years), whereas elder patients may need 1000 mg. Further dosage recommendations are given. To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder.
                A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition.
                After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily.
                Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder. To evaluate the efficacy, safety and tolerability of tolterodine compared to placebo in patients with an overactive bladder.
                A double-blind, multi-centre phase III study in France and Belgium 251 patients with overactive bladder symptoms, and urodynamically verified detrusor overactivity, were randomised to receive 4-week treatment with either placebo or tolterodine 1 or 2mg twice daily (bd). Efficacy was evaluated from patient micturition diaries. Safety and tolerability endpoints were also evaluated.
                After 4-week treatment, the number of incontinence episodes/24h decreased significantly relative to placebo in the tolterodine 1 and 2 mgbd groups (P=0.045 and P=0.0089, respectively). Both dosages of tolterodine increased volume voided per micturition compared with placebo (P=0.055 and P=0.056, respectively), although significant decreases in micturition frequency were not apparent. Tolterodine was safe and well tolerated, few patients were withdrawn due to adverse events. Dry mouth, mainly of mild-to-moderate intensity, was the most common adverse event. No clinically relevant changes in blood pressure or laboratory safety variables were reported.
                Tolterodine is effective, safe and well tolerated for the treatment of symptoms of an overactive bladder, particularly urge incontinence. To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder.
                This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals.
                Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (P <0.0079) and pad usage (P <0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comparable for the two active groups and the placebo group. No safety concerns were noted.
                Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation. In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of "active drugs" and superior to no treatment at all. We analyze the efficacy of tolterodine extended release (ER) for overactive bladder in patients with severe incontinence.
                Patients with urinary frequency (8 micturitions or greater per 24 hours), urge incontinence (5 episodes or greater a week) and symptoms of overactive bladder for 6 months or greater were randomized to treatment with 4 mg tolterodine ER once daily or placebo for 12 weeks. Severe incontinence was defined as 21 episodes or greater per week at baseline. Changes in the number of incontinence episodes per week and micturition frequency after 12 weeks were compared between treatments.
                A total of 986 patients were eligible for this post-hoc analysis. After 12 weeks tolterodine ER produced a significant absolute median reduction in incontinence episodes per week compared to placebo (9.0 vs 5.0, p <0.0001). For patients with severe incontinence at baseline median absolute and percentage reductions in incontinence episodes per week were significantly greater with tolterodine ER than placebo (21.0 vs 9.5, p <0.0001; 67.6% vs 29.8%, p = 0.022). Micturition frequency decreased (p <0.02) and volume voided per micturition (p <0.0001) increased significantly more with tolterodine ER compared with placebo in these patients. For patients with nonsevere incontinence at baseline median reductions in incontinence episodes per week were also significantly greater with tolterodine ER than placebo (6.0 vs 4.0, p <0.0001; 71.4% vs 38.5%, p = 0.026).
                Patients with more severe incontinence at baseline achieved greater absolute reductions in incontinence with tolterodine compared to those with less severe symptoms. The degree of improvement, as measured by percent change, was comparable across the entire range of baseline incontinence severity strata. Benefits of antimuscarinic therapy may be greater in these patients than previously reported. The study investigated the efficacy and cardiac safety of propiverine in the elderly, because the induction of life-threatening ventricular arrhythmia has been reported for some drugs prescribed in the therapy of urinary incontinence. Ninety-eight patients (21 male, 77 female; 67.7+/-6.3 years of age) suffering from urgency, urge incontinence or mixed urge-stress incontinence were included in the double-blind, multicentre, placebo-controlled, randomized study. After a 2-week placebo run-in period, the patients received propiverine (15 mg t.i.d.) or placebo (t.i.d.) for 4 weeks. Before (V1, V2) and during the treatment period (V3, V4), standard ECGs and 24-hour long-term ECGs were recorded. Propiverine caused a significant reduction of the micturition frequency (V2: 8.7+/-4.2, V4: 6.5+/-3.2 ml; p< or =0.01), reflected in a significant increase in the average micturition volume (V2: 163.5+/-65.9, V4: 216.3+/-101.5 ml; p< or =0.01) and a significant decrease in episodes of incontinence (-54%; p = 0.048). These findings were confirmed by the overall assessment at V4, in which approximately 90% of patients under propiverine either had no urge incontinence or urge symptoms, or showed improvement. Resting and ambulatory electrocardiograms indicated no significant changes. Neither the frequency-corrected Q-T interval nor other cardiac parameters were relevantly altered. The frequency of cardiac events (Lown classes IVa/b) was random, revealing no difference between placebo and propiverine. The incidence of adverse events was very low (2% dryness of the mouth under propiverine) and confirmed by the findings from the quality of life questionnaires. A favourable benefit-risk ratio without the induction of any cardiac arrhythmia in the treatment of elderly patients suffering from urgency, urge incontinence or combined urge-stress incontinence is therefore proven for propiverine. To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily.
                This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily.
                Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine.
                In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies. This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks' treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance. To compare the efficacy of penthienate with that of propantheline and placebo for treatment of primary idiopathic detrusor instability.
                Two prospective, randomised, crossover trials (double-blind for penthienate versus placebo and non-blinded for penthienate versus propantheline).
                Urology Clinic of Prince Henry Hospital, Sydney, NSW (an outpatient clinic of a tertiary referral hospital), in 1993-1994.
                Neurologically intact patients with urodynamically proven detrusor instability, urgency and urge incontinence, but no stress incontinence (20 participated in the penthienate/placebo trial and 23 in the penthienate/propanthelin trial).
                Cystometrography results before and after treatment; frequency and volumes of urine voided in weeks 1 and 4 of treatment; and patient scores for degree of continence, side effects, efficacy and acceptability of treatment.
                Penthienate (5 mg), propantheline (15 mg) or placebo (all three times a day) for 4 weeks.
                Penthienate produced significantly greater improvements than placebo in frequency (daytime, P = 0.002; and night-time, P = 0.02), incontinence scores (P = 0.002) and amplitude of unstable detrusor contractions, when present (P = 0.01), and significantly increased diurnal and nocturnal bladder capacity, both on cystometrography (P = 0.003) and by voiding-diary records (P < 0.001). It also increased residual urine volume over the baseline level, but not significantly. Side effects, especially dry mouth, were common with penthienate, and one patient developed urinary retention. Penthienate was significantly better than propantheline in improving cystometric capacity (P = 0.03), and reducing the amplitude of unstable detrusor contractions (P = 0.01), and was perceived as more effective by patients for frequency, nocturia and incontinence.
                Penthienate (5 mg three times a day) was objectively and subjectively significantly better than both placebo and propantheline (15 mg three times a day) for treatment of primary idiopathic detrusor instability. About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond.
                A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling.
                There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations.
                Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration. Tolterodine is a new competitive muscarinic receptor antagonist developed for the treatment of the unstable bladder. A total of 242 patients were enrolled in a multicenter, multinational, randomized, double-blind, placebo-controlled study conducted over a period of 4 weeks in patients with detrusor overactivity and symptoms of frequency, urgency, and urge incontinence. The objective of the study was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d. versus placebo. At week 4 a statistically significant increase in the volume at first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally well tolerated. The incidence of dry mouth, as the most commonly reported adverse event, was only 9% and of mild to moderate intensity. Seventy-two women with proven detrusor instability completed a novel clinical trial of the new anticholinergic emepronium carrageenate (Cetiprin novum), which allowed for dose titration. The tolerated dose has been shown to correlate with the severity of symptoms. Statistically significant improvement was achieved in symptomatic and urodynamic parameters without serious side effects. To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence).
                A double-blind, placebo-controlled, multicentre study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks' treatment.
                A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of < or = 2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings.
                The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1-2 mg twice daily. Unstable bladder is a frequent syndrome in women and is due in the most part because of detrusor involuntary contractions, mainly due to detrusor denervation, which produces voiding hypersensitivity and loss of cortical inhibition control, clinical manifestations are: frequency, nicturia, urgency and urge incontinence. Historically the most effective treatment has been muscular relaxing agents and anticholinergic agents. We present a prospective, double blind, cross, placebo control study to evaluate efficacy and tolerance of oxybutynin in women with unstable bladder. We included 44 adult women with unstable bladder, 22 unitially received oxybutynin 5 mg t.i.d. and 22 placebo 5 mg t.i.d. aleatory in both groups through 6 weeks, later wash-out period was performed and those women in which initially received oxybutynin were administered placebo and those women in which initially received placebo, were administered oxybutynin, for another six weeks. Five patients which initiated the study with oxybutynin abandoned the study, 2 of them for intolerance and 3 for unknown causes. Two women in which initially received placebo abandoned follow-up too. A total of 74 subjects (37 for each branch of study) had an age average of 51.7. Symptoms scoring decreased from 13 to 11 and 6 points with placebo and oxybutynin respectively (p = 0.001). The analog visual scale of symptoms decreased from 77% to 62.5% and 40% with placebo and oxybutynin respectively (p = 0.003). The overall rate of improvement evaluated through symptoms scoring was from 27% with placebo and 72.9% with oxybutynin (p = 0.000) and evaluated through analog visual scale of symptoms was from 40% with placebo and 78.3% with oxybutynin (p = 0.002). The vesical volume at first voiding sensation increased from 129 ml to 134 ml and 187 ml with placebo and oxybutynin respectively (p = 0.021) and the maximum cystometric capacity increased from 231 ml to 236 ml and 301 ml with placebo and oxybutynin respectively. The most frequent adverse effect in both groups was mouth dryness and it presented in 7 (19%) and 34 (91%) patients with placebo and oxybutynin respectively (p = 0.000). Only 5 of 44 patients (11.3%) with oxybutynin and 2 of 44 patients (4.4%) with placebo abandoned follow up (p = 0.14). We concluded that oxybutynin improve significantly the unstable bladder symptoms in women, possibly by increasing functional bladder capacity and decreasing voiding sensitivity, with good tolerance of mouth dryness in the majority of patients. The results of a double-blind controlled trial using oxybutynin chloride in 30 patients are described. Twenty-three patients completed the study; 17 of these had symptomatic improvement and 9 patients had urodynamic improvement. Seventeen patients had significant side effects. The effect of the anticholinergic agent, emepronium bromide (Cetiprin), was studied in a double blind crossover study of a group of elderly patients with urinary incontinence and uninhibited bladder contractions during cystometry. There was no statistically significant difference between the subjective effect of emepronium bromide and that of placebo, and no change in the cystometric parameters. The overall subjective cure or improvement rate was 79%. The effect of anticholinergic drugs in the treatment of urinary incontinence in elderly patients with uninhibited bladder contractions might to some extent be due to an improvement in the patients' understanding and acceptance of the bladder disorders. To examine the efficacy and tolerability of antimuscarinic therapy in women with urge-predominant mixed incontinence.
                This was a double-blind, randomized, placebo-controlled trial comprising 854 women with urge-predominant mixed incontinence, including urge incontinence (five or more episodes per week), urinary frequency (eight or more micturitions on average in 24 hours), and urgency in combination with stress incontinence. Women received 8 weeks of treatment with tolterodine tartrate extended-release (ER) 4 mg or placebo once daily. The outcome measures included urge incontinence episodes per week, stress incontinence episodes per week, micturition frequency per 24 hours, urgency episodes per 24 hours, volume voided per micturition, patient perception of bladder condition, and assessment of treatment benefit.
                After 8 weeks, tolterodine ER produced a statistically significant decrease in the weekly urge incontinence episodes compared with placebo (-12.3 versus -8.0; P <0.0001). Other micturition variables improved significantly more with tolterodine ER. No difference was found between treatment groups regarding the change in the number of stress incontinence episodes. A significantly greater proportion of patients receiving tolterodine ER than those receiving placebo reported improvement in bladder condition (61% versus 46%; P <0.001) and treatment benefit (76% versus 55%; P <0.001). After 8 weeks, the tolterodine ER group had experienced statistically significant improvements compared with the placebo group in 9 of 10 quality-of-life domains. The frequency of adverse events was similar between treatment groups.
                Tolterodine ER is an effective treatment of urge urinary incontinence, frequency, and urgency in women with concomitant stress urinary incontinence. The efficacy of tolterodine ER in reducing urge incontinence episodes was unaffected by the presence of stress incontinence. The results of this study support the first-line use of antimuscarinic therapy to treat the urge incontinence component of urge-predominant mixed incontinence. To evaluate the efficacy, tolerability and safety of darifenacin, a once-daily M3) selective receptor antagonist (M3 SRA), in patients with overactive bladder (OAB).
                This multicentre, double-blind, placebo-controlled, parallel-group study enrolled 561 patients (19-88 years; 85% female) with OAB symptoms for >6 months, and included some patients with prior exposure to antimuscarinic agents. After washout and a 2-week placebo run-in, patients were randomised (1:4:2:3) to once-daily oral darifenacin controlled-release tablets (3.75 mg [n=53], 7.5 mg [229] or 15 mg [n=115]) or matching placebo (n=164) for 12 weeks. Patients recorded daily incontinence episodes, micturition frequency, bladder capacity (mean volume voided), frequency of urgency, severity of urgency, incontinence episodes resulting in change of clothing or pads and nocturnal awakenings due to OAB using an electronic diary during weeks 2, 6 and 12 (directly preceding clinic visits). Tolerability data were evaluated from adverse event reports.
                Darifenacin 7.5 mg and 15 mg had a rapid onset of effect, with significant improvement compared with placebo being seen for most parameters at the first clinic visit (week 2). This effect was sustained through week 12. At this time the number of incontinence episodes per week was reduced from baseline by 67.7% with darifenacin 7.5 mg and 72.8% with darifenacin 15 mg compared with 55.9% with placebo (p=0.010 and p=0.017, respectively, versus placebo). The 3.75 mg group (null dose arm) was included for proof of concept of dose flexibility, therefore formal sample sizing and statistical analysis were not performed for this group. Darifenacin 7.5 mg and 15 mg, respectively, were significantly superior to placebo for improvements in micturition frequency (p<0.001, p<0.001), bladder capacity (p<0.040, p<0.001), frequency of urgency (p<0.001, p=0.005), severity of urgency (p<0.001, p=0.002) and number of incontinence episodes leading to a change in clothing or pads (p<0.001, p=0.002). There was no significant reduction in nocturnal awakenings due to OAB. The most common adverse events were mild-to-moderate dry mouth and constipation. However, no patients withdrew from the study as a result of dry mouth and discontinuation related to constipation was rare (0.6% placebo versus 0.9% darifenacin). In addition, there was a low need for laxative use, with no difference between the darifenacin groups and those taking placebo. There were no reports of blurred vision and the CNS and cardiac safety profile was comparable to placebo.
                Darifenacin significantly improves the major symptoms of OAB. No significant CNS (primarily M1-receptor mediated) adverse events or cardiac (primarily M2-receptor mediated) adverse events were identified in this study, as may be predicted from the M3 selective receptor profile of darifenacin. Twenty-four incontinent elderly institutionalized subjects with detrusor instability participated in a double-blind placebo-controlled trial of oxybutynin chloride. Patients were randomly assigned to oral oxybutynin 5 mg or placebo twice daily. Administration continued for 8 days; a 6-day washout period was followed by the alternative treatment. Incontinence was recorded using a bedside electronic monitor. Four subjects withdrew because of side-effects before completing the trial. There were no clinically significant differences between the oxybutynin and placebo treatments. Both groups experienced side-effects, of which dry mouth was the commonest. Thus, oxybutynin does not appear to be more effective than placebo for the treatment of incontinence in the presence of detrusor instability in elderly institutionalized people. To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence.
                Randomized, double-blinded, placebo-controlled, clinical trial. Eligible patients were stratified according to type of incontinence (urge only vs mixed urge and stress) and severity of incontinence (frequency of accidents as documented in bladder diary).
                University-based outpatient geriatric medicine clinic.
                One hundred five ambulatory, nondemented, community-dwelling women; mean age 67.0 (range 55-91); 98% white, 2% African American.
                Four sessions (over 8 weeks) of biofeedback-assisted behavioral training, drug treatment with individually-titrated oxybutynin chloride, or a placebo control condition.
                Two-channel cystometry was performed to determine threshold volumes for first desire to void (FDV), strong desire to void (SDV), bladder capacity, and the volume at which detrusor instability (DI) or leakage occurred, before randomization and after completion of treatment. Two-week bladder diaries were used before and after treatment to document episodes of incontinence and voiding frequency.
                Bladder capacity increased by 68.9 mL in the oxybutynin group (P <.001) and 17.3 mL in the behavior group and decreased 6.0 mL in the control group. SDV increased 69.9 mL in the oxybutynin group (P <.001), 40.5 in the behavior group (P <.05), and 7.8 mL in the control group. FDV increased by 44.4 mL in the oxybutynin group (P <.001), 18.8 mL in the behavior group, and 8.9 mL in the control group. One of seven patients who presented with DI (12.0%) resolved in the behavior group, seven of eight (87.5%) resolved in the oxybutynin group, and seven of 12 (58.3%) resolved in the control group. These differences were not statistically significant. Voiding frequency was significantly reduced after treatment in both the behavior and the oxybutynin group. Behavioral training resulted in a mean 82.3% reduction in frequency of accidents, oxybutynin (final doses 2.5 mg daily to 5 mg three times a day) resulted in a mean 78.3% reduction, and the control condition resulted in a mean 51.5% reduction (P =.002). Although oxybutynin and behavioral treatment were both effective, and oxybutynin increased SDV and bladder capacity, the structural equation modeling did not demonstrate that the clinical improvement was mediated through the effects of these treatments on urodynamic or voiding frequency measures.
                Studies using more-complex urodynamics and studies with larger sample sizes are needed to better characterize changes in bladder function and explore other urodynamic changes that may accompany treatment. In addition, other factors, both physiological and behavioral, need to be explored as mechanisms by which conservative therapies improve urge incontinence. To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients.
                A 12-week double-blind, placebo-controlled clinical trial.
                An international study conducted at 167 medical centers.
                One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency.
                Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks.
                Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older.
                Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87).
                The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age. Urinary incontinence is a common condition caused by many factors with several treatment options.
                To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women.
                Randomized placebo-controlled trial conducted from 1989 to 1995.
                University-based outpatient geriatric medicine clinic.
                A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia.
                Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition.
                Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment.
                For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% "much better" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups.
                Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence. To evaluate the effect of once-daily, extended-release tolterodine on urinary urgency in patients with overactive bladder.
                Patients with urinary frequency (eight or more micturitions per 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral treatment with tolterodine extended release 4 mg once daily (n=398) or placebo (n=374) for 12 weeks. Efficacy was assessed by use of patient perception evaluations.
                The results presented are a secondary analysis of this double-blind, placebo-controlled study. Of patients treated with tolterodine extended release, 44% reported improved urgency symptoms (compared with 32% for placebo), and 62% reported improved bladder symptoms (placebo, 48%) (both P<.001 compared with placebo). The odds of reducing urgency and improving bladder symptoms were 1.68 and 1.78 times greater, respectively, for patients in the tolterodine extended release group than for patients receiving placebo. In response to urgency, there was a more than six-fold increase in the proportion of patients able to finish a task before voiding in the tolterodine extended release group. The proportion of patients unable to hold urine upon experiencing urgency was also decreased by 58% with tolterodine, compared with 32% with placebo (P<.001). The proportion of patients reporting "much benefit" from treatment was greater for tolterodine extended release than for placebo (43% versus 24%; P<.001). The only adverse events with an incidence of greater than 5% were dry mouth, headache, and constipation, with only dry mouth markedly more frequent with tolterodine than with placebo.
                Tolterodine extended release has demonstrable efficacy in reducing the severity of urinary urgency and is associated with improvements in overactive bladder symptoms that are meaningful to patients. In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin.
                The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition.
                Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo).
                In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose. Trospium chloride is an anticholinergic agent with predominantly peripheral nonselective antimuscarinic activity lacking central nervous system effects. It has no known drug-drug interactions, an advantage for patients taking many medications. Because these qualities may provide added benefit when treating patients with symptoms associated with overactive bladder (OAB) and urge incontinence, we studied the effectiveness of trospium in treating these conditions.
                Patients with OAB with urge incontinence were randomized 1:1 to 20 mg trospium twice daily or placebo in this 12-week, multicenter, parallel, double-blind, placebo controlled trial. Dual primary end points were change in average number of toilet voids and change in urge incontinent episodes per 24 hours. Secondary efficacy variables were change in average of volume per void, voiding urge severity, urinations during day and night, time to onset of action and change in Incontinence Impact Questionnaire.
                A total of 523 patients were entered at 51 sites. Trospium significantly decreased average frequency of toilet voids and urge incontinent episodes compared to placebo. It significantly increased average volume per void, and decreased average urge severity and daytime frequency. All effects occurred by week 1 and all were sustained throughout the study. Nocturnal frequency decreased significantly by week 4 and Incontinence Impact Questionnaire scores improved at week 12. Trospium was well tolerated.
                Trospium was found to have sustained effectiveness beginning at the end of week 1 in decreasing the number of voids, urge incontinent episodes, total daily micturitions and urge severity, and in increasing volume per void. It also improved symptoms of OAB and quality of life. In a multicentre placebo-controlled double-blind study 61 patients with spinal cord injuries and detrusor hyperreflexia were treated: 20 mg trospium chloride was given twice daily over a period of 3 weeks. Pre- and posttreatment urodynamic measurements demonstrated large improvements in maximum cystometric capacity (mean = 138.1 ml), decreased maximum detrusor pressure (mean = -37.8 cm H2O) and an increase in compliance (mean = 12.1 ml/cm H2O) in the treatment group. Urodynamic parameters in the placebo group remained substantially unchanged. Comparisons between the two groups revealed highly significant differences for these parameters (all, p less than 0.001). No effect on maximum flow rate and residual urine was detected in either group. The incidence of spontaneously reported side-effects was extremely low and comparable for both groups. To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder.
                Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study.
                Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland.
                One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours).
                Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks.
                Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours.
                The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo.
                Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder. To compare the efficacy and safety of an oxybutynin transdermal delivery system (OXY-TDS) and oral, long-acting tolterodine (TOL-LA) with placebo in previously treated patients with urge or mixed urinary incontinence.
                After withdrawal of their current antimuscarinic therapy, 361 adult patients were randomized to 12 weeks of double-blind, double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day, daily TOL-LA 4 mg, or placebo. Evaluations included change from baseline in patient urinary diary symptoms, incontinence-specific quality of life, and safety.
                OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes (median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo; P <0.05), increased the average void volume (median change 24 and 29 mL versus 5.5 mL, P <0.01), and improved quality of life (incontinence impact questionnaire [IIQ] total score, P <0.05; Urogenital Distress Inventory Irritative Symptom subscale, P <0.05) compared with placebo. The most common adverse event for OXY-TDS was localized application site pruritus (14% versus 4% placebo) accompanied by a low incidence of systemic side effects (eg, dry mouth 4.1%). Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment (dry mouth 7.3% versus 1.7% placebo, P <0.05).
                OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence. OXY-TDS improves systemic safety with regard to anticholinergic side effects. Local skin irritation occurs in some OXY-TDS patients. To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a randomized, double-blind placebo-controlled clinical trial.
                In all, 366 patients (149 on propiverine, 145 oxybutynin and 72 placebo, ratio 2:2:1) with urgency and urge incontinence were recruited in 32 study centres. Propiverine (group 1, 15 mg three times daily), oxybutynin (group 2, 5 mg twice daily) or placebo (group 3) were administered for 4 weeks, using the double-dummy technique. The dosages were selected specifically to compare the tolerability profile of propiverine with the commonly used therapeutic dosage of oxybutynin. Tolerability was assessed by directly questioning the patients about adverse events at four visits (V-1 before and V0 after a 1-week 'washout' period, V1 after 1 week and V4 after 4 weeks of treatment) during a 5-week surveillance period, and by tolerability ratings of the physicians. Efficacy was assessed using urodynamics at V0 and V4, evaluating the cystometric bladder capacity at maximal and first desire to void, and postvoid residual urine, according to the criteria of the International Continence Society. Additionally, a voiding protocol, overall assessment of clinical symptomatology and efficacy ratings by the physicians were documented.
                A remarkably high percentage of adverse events was reported in the washout period (VO: 13%, 16% and 18% in groups 1-3, respectively). At V4, the clinically most relevant symptom (dry mouth) occurred in 53% of patients in group 1, in 67% of group 2 and in 28% of group 3. Furthermore, dry mouth was less severe in group 1 than group 2. In contrast to groups 2 and 3, only patients in group 1 showed increasing tolerability during the treatment (from V1 to V4). These tolerability results were further supported by the overall tolerability assessment ('very good' or 'good' tolerability in 67% of group 1, in 59% of group 2 and in 83% of group 3). The urodynamic assessment of efficacy (comparing V0 and V4) showed a statistically significant increase in the mean (sd) maximal cystometric bladder capacity in group 1, being 222 (77) mL at V0 and 311 (125) mL at V4, an increase of 89 (108) mL, and in group 2, at 226 (75) mL and 322 (123) mL, an increase of 96 (106) mL, compared with group 3, at 211 (77) mL and 263 (93) mL, an increase of only 52 (92) mL. The cystometric bladder capacity at first desire to void also increased in group 1 (93 to 160 mL) and group 2 (89 to 160 mL), whereas in group 3 there were only minor changes (93 to 120 mL). Changes in the residual urine volume within and between the treatment groups were minimal and clinically irrelevant. The overall assessment of efficacy showed significant differences between the drugs when compared with placebo.
                Propiverine is a safe and effective drug in the treatment of urgency and urge incontinence; it is as effective as oxybutynin, but the incidence of dry mouth and its severity is less with propiverine than with oxybutynin. The availability of alternative pharmacotherapeutics such as propiverine should reduce the therapeutic failure rate and improves the success rate in the treatment of patients suffering from urgency and urge incontinence. Overactive bladder (OAB) has a significant impact on a patient's health-related quality of life (HRQoL). This study assessed the HRQoL of Japanese OAB patients following 12 weeks' treatment with tolterodine extended release (ER) or oxybutynin. A total of 293 patients with symptoms of OAB were randomized for treatment with tolterodine ER 4 mg once daily (n=114), oxybutynin 3 mg three times daily (n=122) or a placebo (n=57). Treatment efficacy and safety assessments were made over the 12-week period. HRQoL was assessed using the King's Health Questionnaire (KHQ). Patients receiving tolterodine ER or oxybutynin showed a significant (P<0.05) improvement in the Incontinence Impact, Role Limitations and most other KHQ domains compared with the placebo. These changes in HRQoL corresponded with significant (P<0.05) improvements in micturition diary variables for patients receiving tolterodine ER and oxybutynin compared with placebo. Our findings demonstrate that Japanese OAB patients receiving tolterodine ER or oxybutynin experienced overall improvement in their quality of life. Oxybutynin hydrochloride (3 mg) was compared with placebo by randomised, double-blind crossover trial in 53 females with idiopathic detrusor instability. Symptoms were cured or markedly improved in 60% of patients on oxybutynin and 2.3% on placebo. During the first treatment period, oxybutynin reduced the frequency of voiding by 35%, compared with 9% for placebo. Oxybutynin gave a significantly greater improvement than placebo in volume at the first desire to void (70 ml increase versus 7.7 ml), maximum filling-phase detrusor pressure (17 cm H2O reduction versus no benefit) and cystometric capacity (104 ml increase versus 7.0 ml). A marked oxybutynin carry-over effect was seen during the second treatment period. Side effects from the 3 mg dose of oxybutynin caused 7.5% of subjects to discontinue therapy. To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily.
                The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for > or = 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void.
                In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (-1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (-2.85, -51.9%) and 10 mg (-3.07, -54.7%; both P < 0.001), but not with tolterodine (-2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (-1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (-1.42; P = 0.008) and 10 mg (-1.45; P = 0.0038). Compared with placebo (-1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (-1.88, -15%; P = 0.0145), solifenacin 5 (-2.19, -17%) and 10 mg (-2.61, -20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments (P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin.
                Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB. Idiopathic detrusor instability is a common cause of incontinence in the elderly for which anticholinergic agents are regularly prescribed. Oxybutynin chloride combines anticholinergic action with direct muscle relaxant properties. We performed a double blind placebo controlled fixed dose cross over study of oxybutynin chloride in post-menopausal women suffering from detrusor instability. We found oxybutynin chloride significantly more effective than placebo at reducing the symptoms of urgency and urge incontinence and more effective at reducing the height of the highest unstable detrusor contraction. This was at the expense of an increased residual urine and considerable side effects. We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity.
                In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects.
                After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events.
                Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects. The aim of this study was to examine the efficacy of oxybutynin plus bladder training in the treatment of detrusor instability in frail elderly patients living independently in the community. It was a randomized, double-blind, placebo-controlled parallel-group trial of oxybutynin in 57 elderly patients (mean age 82.2, SD 6.06), with frequency and incontinence due to detrusor instability. After a 2-week run-in period patients received a bladder training and drug or placebo for the next 6 weeks. Outcome measures were changes in frequency and incontinence, recorded throughout on diary charts, and subjective evaluation of symptoms ('better'/'not better', and using a four-point scale 'cure' to 'no change'). Oxybutynin was superior to placebo in reducing daytime frequency [95% confidence interval (CI) of difference in change in frequencies totalled over 14 days was -27.0, -6.0; p = 0.003] and in producing subjective benefit (at day 29 only), when 24/28 (86%) patients on oxybutynin described benefit compared with 16/29 (55%) on placebo (p = 0.02). There was no difference between the groups in reduction of incontinent episodes. The median dose of oxybutynin titrated for therapeutic effect was 5 mg/day, and for placebo 10 mg/day (CI of difference 0.001, 5.001; p = 0.05). Side-effects reported were of similar frequency (50%) in the two groups. We conclude that oxybutynin with bladder training is superior to bladder training alone in reducing frequency due to detrusor instability in very elderly people living at home. The Authors carried out a random double-blind trial on 30 patients affected by idiopathic urge incontinence with oxybutynin chloride (15 mg/die) and placebo for two 20 day therapeutical cycles. The 24 patients who completed the trial oxybutynin chloride induced statistically significant effects--compared to placebo too--both on the subjective symptoms (reduction or disappearance of the urgency in 14 cases - 60.8% - and of urge incontinence in 16 cases - 76.1%) and on the objective symptoms showed by cystomanometry (increased bladder capacity at the FD and VSD in 14 and 15 cases, respectively; absence of involuntary contraction in 9 cases and normal or reduced detrusor pressure at the VSD in 13 out of 16 cases). Improvements, though less significant, were also obtained with the placebo. Clinical efficacy and adverse effects of oxybutynin and propantheline in the treatment of symptoms related to detrusor hyperactivity were studied in a randomized, controlled, double-blind multicenter trial. Of 169 patients entered into the study 154 were evaluable for statistical analysis. Mean grade of improvement (visual analogue scale) was significantly higher with oxybutynin (58.2%) versus propantheline (44.7%) and placebo (43.4%). Mean bladder volume at first involuntary cystometric contraction was significantly increased with oxybutynin (+57.0 ml.) versus placebo (-9.7 ml.). Mean maximum cystometric bladder capacity was also significantly increased with oxybutynin (+80.1 ml.) versus placebo (+22.5 ml.). Rate of inquired possible adverse effects was significantly higher for oxybutynin (63%) versus propantheline (44%) and placebo (33%). However, only 5 patients dropped out of the study because of adverse effects (oxybutynin 2 and propantheline 3). No serious or lasting adverse effects were encountered with dryness of the mouth being the major complaint. Oxybutynin has statistically significant effects on subjective symptoms and objective urodynamic parameters in patients with detrusor hyperactivity compared to propantheline.
The use of anticholinergic drugs by people with overactive bladder syndrome results in statistically significant improvements in symptoms. Recent trials suggest that this is associated with modest improvement in quality of life. Dry mouth is a common side effect of therapy but did not seem to have an effect on the numbers of withdrawals. It is not clear whether any benefits are sustained during long-term treatment or after treatment stops.