新型抗胆碱能药物托特罗定治疗膀胱过度活动症的临床研究

目的　评价新型抗胆碱药物托特罗定治疗膀胱过度活动症的有效性和安全性。　方法　采用随机、双盲、双模拟、平行对照的方法对207例膀胱过度活动症患者进行托特罗定与奥昔布宁的对比研究,服药方法每日2次,每次托特罗定2mg或奥昔布宁5mg。　结果　治疗6周后,托特罗定组(103例)24h平均排尿次数减少(3.0±3.4)次,其中尿失禁患者的平均尿失禁次数减少(1.5±1.8)次;奥昔布宁组(104例)治疗后24h平均排尿次数减少(4.6±6.4)次,平均尿失禁次数减少(2.4±2.1)次,两组间差别无显著性意义(P>0.05)。托特罗定组患者副作用发生率66.9%,其中口干为55.3%;而奥昔布宁组发生率为87.5%,口干为76.9%,两组间差别有显著性意义(P<0.05)。　结论　托特罗定是治疗膀胱过度活动症的有效药物,疗效与奥昔布宁相同,但不良反应明显低于奥昔布宁。     

Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial

PURPOSE: We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland. MATERIALS AND METHODS: In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments. RESULTS: Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment. CONCLUSIONS: Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.     

Urodynamic verification of an overactive bladder is not a prerequisite for antimuscarinic treatment response

OBJECTIVE: To investigate the place of urodynamics in the evaluation of patients with symptoms of the overactive bladder by comparing the response to antimuscarinic therapy in those with and with no urodynamically verified symptoms. PATIENTS AND METHODS: In a prospective observational study, 356 female patients with urinary frequency (> or = 8 voids/24 h) and urgency, with or without urge incontinence, underwent cystometry. Patients were diagnosed with detrusor instability if there were spontaneous, uninhibited increases in detrusor pressure during bladder filling. All patients, regardless of urodynamic findings, were subsequently treated with oxybutynin 2.5 mg twice daily and bladder retraining. The outcome was evaluated as the change in urinary frequency and incontinence episodes after 6-8 weeks of treatment. RESULTS: Among 352 evaluable patients, 266 (76%) had detrusor instability on cystometry and the remainder did not. There was no significant between-group difference in mean age, urinary frequency or the number of incontinence episodes at presentation. Both groups improved equally well during oxybutynin and bladder retraining therapy; after 6-8 weeks there was no significant between-group difference for the mean change from baseline in urinary frequency or incontinence episodes. Tolerability profiles were comparable for the two groups. CONCLUSION: Patients with symptoms of an overactive bladder, but apparently normal urodynamic findings, respond equally well to antimuscarinic therapy as those with urodynamically verified symptoms. Such findings cast further doubt on the clinical validity of using invasive urodynamic procedures to characterize patients with irritative lower urinary tract symptoms before starting antimuscarinic therapy.     

Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial

OBJECTIVE: To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB). PATIENTS AND METHODS: Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed. RESULTS: In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients. CONCLUSION: Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.     

A comparison of extended-release oxybutynin and tolterodine for treatment of overactive bladder in women

Women with urge or mixed incontinence were randomized to a daily dose of 10 mg extended-release oxybutynin chloride (qd) or tolterodine tartrate 4 mg (2 mg bid) for 12 weeks. Subjects completed 7-day voiding diaries at baseline and at 12 weeks. A total of 315 women were treated. At the end of the study, extended-release oxybutynin chloride was more effective than twice-daily tolterodine tartrate as measured by urge and total incontinence episodes (p=0.038, p=0.030, respectively). Overall, the reduction in micturition frequency between groups was not significantly different. In women aged 64 years and younger (comprising 63% of the population) extended-release oxybutynin was more effective than tolterodine for urge (p=0.005) and total incontinence (p=0.005), and for micturition frequency (0.024). Adverse events were infrequent, mostly mild, and similar between treatment groups. We concluded that daily extended-release oxybutynin chloride (10 mg) was more effective than tolterodine tartrate (2 mg bid) in treating urge and total incontinence. The incidences of dry mouth, CNS events, and other adverse events were similar for both drugs.     

Tolterodine: As effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder

BACKGROUND: This double-blind, multicenter study compared the efficacy and tolerability of tolterodine (Pharmacia, Los Angeles, USA) with that of oxybutynin (Alza, Palo Alto, USA) in Asian patients with overactive bladder. METHODS: Two-hundred-and-twenty-eight adults with overactive bladder symptoms were randomized to receive tolterodine 2 mg twice daily (bid) (n = 112) or oxybutynin 5 mg bid (n = 116). After 8 weeks' treatment, changes in micturition diary variables, patients' perception of treatment benefit, and tolerability endpoints were determined. RESULTS: The mean (+/- SD) number of micturitions/24 h decreased by 2.6 +/- 2.9 (-21%) with tolterodine and 1.8 +/- 4.2 (-15%) with oxybutynin (both P = 0.0001 vs baseline). The mean number of incontinence episodes/24 h decreased by 2.2 +/- 2.3 (-85%) in the tolterodine group and by 1.4 +/- 1.8 (-58%) in the oxybutynin group (both P = 0.0001 vs baseline). Patient perception of treatment benefit was over 70% in each treatment group. Adverse events were significantly lower in the tolterodine group compared with oxybutynin-treated patients (55% vs 82%; P = 0.001). Dry mouth was reported by significantly fewer patients on tolterodine, compared with oxybutynin (35% vs 63%; P = 0.001) and withdrawals due to adverse events were lower in the tolterodine group than with those treated with oxybutynin (10% vs 16%). There were no safety concerns. CONCLUSIONS: Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the treatment of Asian patients with overactive bladder, and shows significantly better tolerability. This may enhance compliance during long-term treatment.     

Efficacy and safety of tolterodine in people with neurogenic detrusor overactivity

OBJECTIVE: To compare tolterodine with oxybutynin and placebo in people with neurogenic detrusor overactivity. DESIGN: Prospective, randomized, double-blind, crossover trial plus open-label comparative stage. PARTICIPANTS: Ten participants with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis who used intermittent catheterization. METHODS: Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes per day, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison: tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each at self-selected doses (SSDs). RESULTS: Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P < 0.0005) and reducing incontinence (P < 0.001), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD was comparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity. The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantly when comparing tolterodine SSD with oxybutynin SSD (P < 0.05). CONCLUSION: Tolterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improving continence, but with less dry mouth. Tolterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladder volumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effect in this population, but further studies are required.     

Intravesical atropine compared to oral oxybutynin for neurogenic detrusor overactivity: a double-blind, randomized crossover trial

PURPOSE: We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis. MATERIALS AND METHODS: We performed a study to determine the most effective dose of atropine. Eight participants used increasing doses of intravesical atropine during a 12-day period. Bladder diary data showed that the instillation of 6 mg atropine 4 times daily was most effective for increasing bladder capacity (voided/catheter volumes). We then did a randomized, double-blind crossover trial. Participants received 14 days of treatment with oral oxybutynin or with intravesical atropine, followed by 14 days of alternative treatment. Participants recorded a bladder diary and rated side effects and quality of life. The primary outcome variable was bladder capacity. RESULTS: A total of 57 participants with multiple sclerosis completed the study. Average change in bladder capacity was higher in the atropine arm. The mean +/- SD oxybutynin change was 55.5 +/- 67.2 ml, the mean atropine change was 79.6 +/- 89.6 ml and the mean difference between arms was 24.1 ml (95% CI -0.4, 49.7; p = 0.053). Changes in incontinence events and voiding frequency were not statistically different between the arms. Changes in total side effect and dry mouth scores were significantly better in the atropine treatment arm. CONCLUSIONS: Intravesical atropine was as effective as oxybutynin immediate release for increasing bladder capacity and it was probably better with less antimuscarinic side effects. We recommend that intravesical atropine should be made available to patients with neurogenic detrusor overactivity and voiding problems requiring intermittent catheterization as an alternative to oral therapy, which often has troublesome side effects.     

Therapeutic efficacy of extended release oxybutynin chloride,and immediate release and long acting tolterodine tartrate in children with diurnal urinary incontinence

PURPOSE: We compare the tolerability and efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with nonneurogenic diurnal urinary incontinence and symptoms of overactive bladder. MATERIALS AND METHODS: Children with a history of diurnal urinary incontinence were arbitrarily assigned to extended release oxybutynin, immediate release tolterodine or long acting tolterodine. The dose was titrated until effective (onset of complete diurnal urinary continence), maximal recommended dosage was achieved or bothersome anticholinergic side effects developed. An independent observer recorded the dose used, anticholinergic side effects and efficacy of therapy (incidence of urinary frequency, urgency, posturing and urinary incontinence). RESULTS: The study included 86 girls and 46 boys. There were no statistically significant differences among the 3 treatment groups regarding the presence of peripheral or central nervous system anticholinergic side effects. Extended release oxybutynin and long acting tolterodine were significantly more effective at reducing daytime urinary incontinence than immediate release tolterodine (p <0.01 and 0 <0.05, respectively). Extended release oxybutynin was significantly more effective then long acting tolterodine for complete resolution of diurnal incontinence (p <0.05). CONCLUSIONS: Extended release oxybutynin and long acting tolterodine are more effective than immediate release tolterodine in decreasing diurnal urinary incontinence. Extended release oxybutynin chloride is more effective than either immediate or long acting tolterodine for control of daytime urinary incontinence and urinary frequency.     

Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence

PURPOSE: We evaluated the efficacy and safety of an oxybutynin transdermal delivery system (TDS) in a general population of patients with overactive bladder and urge or mixed urinary incontinence. MATERIALS AND METHODS: Following symptom stabilization or treatment withdrawal 520 adult patients were randomized to 12 weeks of double-blind daily treatment with 1.3, 2.6 or 3.9 mg. oxybutynin TDS or placebo administered twice weekly, followed by a 12-week open-label, dose titration period to assess efficacy and safety further. Evaluations included patient urinary diaries, incontinence specific quality of life and safety. RESULTS: A dose of 3.9 mg. daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes (median change -19.0 versus -14.5, p = 0.0165), reduced average daily urinary frequency (mean change -2.3 versus -1.7, p = 0.0457), increased average voided volume (median change 24 versus 6 ml., p = 0.0063) and significantly improved quality of life (Incontinence Impact Questionnaire total score, p = 0.0327) compared with placebo. Average voided volume increased in the daily 2.6 mg. group (19 ml., p = 0.0157) but there were no other significant differences between 1.3 and 2.6 mg. oxybutynin TDS and placebo. The most common adverse event was application site pruritus (oxybutynin TDS 10.8% to 16.8%, placebo 6.1%). Dry mouth incidence was similar in both groups (7.0% versus 8.3%, p not significant). In the open-label period a sustained reduction of nearly 3 incontinence episodes per day was reported for all groups. CONCLUSIONS: Doses of 2.6 and 3.9 mg. oxybutynin TDS daily improve overactive bladder symptoms and quality of life, and are well tolerated. Transdermal oxybutynin is an innovative new treatment for overactive bladder.     

Effectiveness and tolerability of extended-release oxybutynin vs extended-release tolterodine in women with or without prior anticholinergic treatment for overactive bladder

The efficacy and the tolerability of extended-release oxybutynin chloride, 10 mg daily, and extended-release tolterodine tartrate, 4 mg daily, in women with or without prior anticholinergic treatment for overactive bladder (OAB) were compared in a post-hoc analysis of data from the Overactive Bladder: Performance of Extended Release Agents (OPERA) trial. The patient population and study methods have been described previously (Diokno et al., for the OPERA Study Group, Mayo Clin Proc 78:687–695, 2003). Among the group with anticholinergic experience, extended-release oxybutynin was significantly more effective than extended-release tolterodine in reducing micturition frequency at last observation (p=0.052). Complete freedom from urge incontinence was reported by significantly more patients taking oxybutynin than tolterodine at last observation (23.6 vs 15.1%, p=0.038). In addition, among patients completing a full 12 weeks of oxybutynin treatment, significantly greater reductions were observed compared with those taking tolterodine on the primary efficacy variable, number of urge incontinence episodes (p=0.049), and the combined total of urge and non-urge episodes (p=0.012), although the differences between treatment groups were not significant at last observation. In the anticholinergic-naïve group, efficacy and tolerability outcomes were similar across treatments, except that oxybutynin was associated with a significantly lower frequency of micturition at last observation (p=0.035). No efficacy differences favoring tolterodine were observed, and tolerability of the treatments was comparable. Dry mouth (mostly mild to moderate in severity) was reported significantly more often among participants taking extended-release oxybutynin than extended-release tolterodine (32.2 vs 19.2%, p=0.004), but only among those with previous anticholinergic experience. Discontinuation rates were comparably low across groups. The results demonstrate the appropriateness of initiating treatment for OAB with extended-release oxybutynin, particularly in women presenting with incontinence.     

Effects of botulinum toxin B on refractory detrusor overactivity: a randomized, double-blind, placebo controlled, crossover trial

PURPOSE: Open, observational studies of intradetrusor injections of botulinum toxin for detrusor overactivity have reported beneficial effects. We tested the efficacy and safety of botulinum toxin B for the treatment of the overactive bladder in a randomized, double-blind, placebo controlled crossover trial. MATERIALS AND METHODS: A total of 20 patients 18 to 80 years old with detrusor overactivity unresponsive to oral antimuscarinic agents participated in the study. They were injected with either placebo (20 ml normal saline) or botulinum toxin B (5,000 IU diluted up to 20 ml) intravesically in a day case setting. After 6 weeks the treatments were crossed over without washout in line with previous findings. The primary outcome was the paired difference in change in average voided volumes. Frequency, incontinence episodes and paired differences in quality of life measured by the King's Health Questionnaire were the secondary outcome measures. RESULTS: The Wilcoxon signed ranks test was used to test the paired difference in change between treatment phases. Little carryover was noted in the second arm placebo and the placebo data from both arms were included in analysis. There were clinically statistically significant paired differences in the change in average voided volume, urinary frequency and episodes of incontinence between active treatment and placebo (average voided volume: 95% CI difference 16, 122; Z2.5; p = 0.012/weekly frequency: 95% CI -21, -1; Z2.1, p=0.033/weekly incontinence: 95% CI -26, -7; Z3.3; p = 0.001). There were similarly significant paired differences in the change in quality of life affecting 5 domains of the King's Health Questionnaire. CONCLUSIONS: This double-blind, placebo controlled, crossover study provides evidence of the efficacy of botulinum toxin B in the treatment of overactive bladder. Autonomic side effects were observed in 4 patients. The short duration of action will presumably limit the use to patients who have experienced tachyphylaxis with botulinum toxin A.     

Retrospective analysis of efficacy and tolerability of tolterodine in children with overactive bladder

OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine in children with an overactive bladder, treated in a single incontinence centre. MATERIALS AND METHODS: A retrospective analysis of a database of a total of two hundred and fifty-six patients (175 boys and 81 girls, age range 3 years to 17 years, mean age 8.33 years) with urodynamically confirmed bladder overactivity was performed. All children received tolterodine tartrate (dose range of 0.5-4 mg orally). In group I (n=205) tolterodine tartrate replaced anticholinergic drugs (AC) (oxybutinin chloride or oxyphencyclimin hydrochloride). A subgroup of patients switched because of intolerance due to serious adverse events (60.4%) or because of lack of improvement in micturition variables (39.6%). In group II tolterodine was prescribed as initial therapy (n=51). Tolerability was assessed by a standardised questionnaire on adverse events at every outdoor clinic visit. Efficacy assessment was based on micturition diary variables, mean change of maximum bladder capacity and number of incontinence episodes/24 h. RESULTS: The mean treatment time was 9.32 months with a range from 1.5 months to 23.4 months. The final dose was 0.1mg/kg orally daily divided into two doses. In group I central nervous system disorders (81%) were the most common adverse events, 26.2% showed flushing, 12.2% accommodation problems and 25.2% had gastrointestinal complaints (constipation, encopresis, abdominal pain). Withdrawal of the non-selective antimuscarinic drug resulted in total recovery from adverse events.Introduction of tolterodine in group I and II caused no serious adverse events. Nine patients (3.5%) reported side-effects and only two discontinued treatment. There were no reports of flushing, troubles of visual accommodation, hyperpyrexia. In group I we observed a mean decrease in urgency by 38.7%, a mean increase in maximal bladder capacity by 33.6% and the number of incontinence episodes decreased by 64.8%. In group II we observed equivalent values with a significant (p<0.001) change in maximal bladder capacity (49.7%), incontinence episodes (64.8%) and micturition episodes/24 h. CONCLUSIONS: The results of this retrospective analysis suggest that tolterodine is well tolerated in children and offers an effective treatment for urinary symptoms due to overactive bladder. Tolterodine is superior to non-selective antimuscarinic drugs, with respect to adverse events, allowing more compliance and more effective treatment in children.     

Transdermal oxybutynin: sticking to the facts

OBJECTIVES: This article critically reviews all the available published and presented data about transdermal oxybutynin to provide a summary of its efficacy, tolerability, and acceptability. RESULTS: For patients with urge incontinence or mixed incontinence, transdermal oxybutynin offers equivalent efficacy to variable dose oral oxybutynin IR and tolterodine LA 4 mg/d. At present no data are available for patients with frequency and urgency but without incontinence (overactive bladder [OAB] dry). Transdermal oxybutynin offers marked improvements compared with placebo in incontinence episodes, daily urinary frequency, and nocturia. These objective improvements are matched by improvements in quality of life. The rate of anticholinergic side-effects is lower than that for oral anticholinergic preparations. This benefit is offset by a rate of local skin reactions. CONCLUSIONS: The balance of efficacy and tolerability suggests that transdermal oxybutynin should be considered as a potential first-line therapy in OAB or mixed incontinence.     

Clinical Efficacy and Safety of Tolterodine Compared to Oxybutynin and Placebo in Patients with Overactive Bladder

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.     

Efficacy and Safety of Tol Terodine in People With Neurogenic Detrusor Overactivity

Abstract

Objective: To compare tolterodine with oxybutynin and placebo in people with neuragenie detrusor overactivity.

Design: Prospective, randomized, double-blind, crossover trial plus open-label comparative stage.

Participants: Ten participants with neuragenie detrusor overactivity due to spinal cord injury or multiple sclerosis who usedintermittent catheterization.

Methods: Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes perday, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison:tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each atself-selected doses (SSDs).

Results: Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P<0.0005) and reducingincontinence (P<0.001 ), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD wascomparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity.The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantlywhen comparing tolterodine SSD with oxybutynin SSD (P<0.05).

Conclusion: T olterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improvingcontinence, but with less dry mouth. T olterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladdervolumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effectin this population, but further studies are required.     

Does concomitant stress incontinence alter the efficacy of tolterodine in patients with overactive bladder?

PURPOSE: Muscarinic antagonists such as tolterodine are the treatment of choice for overactive bladder (OAB). We determined the impact of concomitant stress incontinence (SI) on the therapeutic effects of tolterodine in patients with OAB with and without concomitant SI. MATERIALS AND METHODS: Data from an open label, observational study involving 2,250 patients with OAB symptoms were analyzed for baseline frequency, urgency and incontinence, and alterations in these symptoms while on 12-week treatment with 2 mg tolterodine twice daily. Data are shown as the mean +/- SD. The statistical significance of differences in treatment effects was determined by multiple regression analysis, adjusting for gender, age and baseline symptom intensity. RESULTS: Concomitant I to III degree SI according to the Stamey grading was present in 31%, 15% and 2% of patients, respectively, and it was associated with increasing basal incontinence, although only III degree SI was associated with greater baseline frequency or urgency. In the overall group tolterodine decreased frequency, urgency and urge incontinence from 12.4 +/- 4.3 to 7.7 +/- 2.7, 8.4 +/- 5.1 to 2.0 +/- 3.0 and 3.4 +/- 4.2 to 0.8 +/- 2.0 episodes daily, respectively. On multiple linear regression analysis I and II degree SI had a minor, if any, effect on this improvement, while III degree SI was statistically associated with a smaller decrease in frequency (by 1.4 +/- 0.4 micturitions daily, p = 0.0002) and incontinence (by 2.1 +/- 0.3 episodes daily, p < 0.0001) but with similar alterations in the number of urge episodes. CONCLUSIONS: Concomitant I or II degree SI has little effect on the efficacy of tolterodine in OAB cases. Only patients with concomitant III degree SI have significantly less improvement.     

Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder in Japanese patients

AIM: To evaluate the long-term safety, tolerability and efficacy of extended-release (ER) tolterodine in Japanese patients completing 12-week treatment in a randomized, double-blind trial comparing tolterodine ER 4 mg once daily, oxybutynin 3 mg three times daily or placebo in patients with overactive bladder. METHODS: Of 293 Japanese patients completing the 12-week study, 188 continued in the open-label trial and received tolterodine ER 4 mg once daily for 12 months, irrespective of previous treatment. The primary objective was to assess the safety of tolterodine ER for up to 52 weeks of treatment and at post-treatment follow-up. Secondary endpoints included changes in micturition diary variables, patient perception of bladder condition and urgency and treatment benefit. RESULTS: Overall, 77% of patients completed 12 months of open-label treatment. Tolterodine ER was well tolerated and the most common adverse event was dry mouth (33.5%). In general, there was no increase in adverse event frequency with long-term treatment compared with short-term treatment. The efficacy of tolterodine ER was maintained over the 12-month period. The complete analysis showed a median reduction in incontinence episodes/week (-92.9%; mean reduction, -77.2%), a mean reduction in micturitions/24 h (-21.3%) and a mean increase in volume voided per micturition (19.6%). Of patients completing the 12-month study, 78.6% reported improvement in patient perception of bladder condition, 52.4% reported improvement in perception of urgency and 89.7% reported treatment benefit. CONCLUSIONS: Favorable safety, tolerability and efficacy of once-daily tolterodine ER was maintained over 12 months in a Japanese overactive bladder patient population.     

THE COST‐EFFECTIVENESS OF SOLIFENACIN VS FESOTERODINE,OXYBUTYNIN IMMEDIATE‐RELEASE,PROPIVERINE, TOLTERODINE EXTENDED‐RELEASE AND TOLTERODINE IMMEDIATE‐RELEASE IN THE TREATMENT OF PATIENTS WITH OVERACTIVE BLADDER IN THE UK NATIONAL HEALTH SERVICE

OBJECTIVE

Please also see BJUI letters on page 586 To assess the cost‐effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review.

METHODS

Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older‐generation treatments, including oxybutynin, and new‐generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta‐analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost‐utility analysis was undertaken using a 1‐year decision‐tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality‐adjusted life‐years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base‐case results.

RESULTS

Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended‐release (ER) and tolterodine immediate‐release (IR), and cost‐effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost‐effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost‐effectiveness ratio of >£30 000/QALY threshold.

CONCLUSIONS

Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost‐effective relative to all other new‐generation agents, but not cost‐effective relative to oxybutynin for frequency and incontinence.