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Aims: To assess the efficacy and tolerability of fesoterodine 8 mg versus tolterodine extended release (ER) 4 mg in subjects with overactive bladder (OAB) stratified by age (<65, 65-74, and ≥75 years)., Methods: This was a post hoc analysis of data from two double-blind trials. Subjects reporting ≥1 urgency urinary incontinence (UUI) episode and ≥8 micturitions/24 hr at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. Subjects completed 3-day bladder diaries, Urgency Perception Scale (UPS), Patient Perception of Bladder Condition (PPBC), and OAB questionnaire (OAB-q) at baseline and week 12. The primary endpoint in both studies was change from baseline to week 12 in UUI episodes., Results: Among subjects <65 years (n = 2,670), improvements in UUI episodes, micturitions, urgency episodes, severe urgency episodes, frequency-urgency sum, UPS, PPBC, and all OAB-q scales and domains were significantly greater with fesoterodine versus tolterodine ER, and diary-dry rates were significantly higher. Among subjects 65-74 years (n = 990), improvements in mean voided volume per void, PPBC, and OAB-q Symptom Bother and Coping were significantly greater with fesoterodine versus tolterodine ER. Among subjects aged ≥75 years (n = 448), improvements in urgency episodes, severe urgency episodes, frequency-urgency sum, UPS, and OAB-q Symptom Bother were significantly greater with fesoterodine versus tolterodine ER. Both active treatments produced significant improvements in most outcomes versus placebo across age groups. Adverse event rates were similar among age groups., Conclusions: Fesoterodine 8 mg consistently improved several OAB-related variables versus tolterodine ER 4 mg in subjects aged <65, 65-74, and ≥75 years, with some differences reaching statistical significance, and was generally well tolerated., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims: To assess the efficacy and safety of pregabalin alone or in combination with tolterodine extended release (ER) in subjects with idiopathic OAB., Methods: This 26-week, multicenter, randomized, double-blind, placebo-controlled, three-period crossover study enrolled women aged ≥ 18 years that were diagnosed with OAB and reported ≥ 8 micturitions/24 hr and ≥ 4 urgency episodes/week on 5-day bladder diary at baseline. Subjects were randomized to 1 of 10 treatment sequences and received three of five treatments, each for 4 weeks with 4-week washout periods: standard-dose pregabalin/tolterodine ER (150 mg twice daily [BID]/4 mg once daily [QD], n=102), pregabalin alone (150 mg BID, n=105), tolterodine ER alone (4 mg QD, n=104), low-dose pregabalin/tolterodine ER (75 mg BID/2 mg QD, n=105), and placebo (n=103). Subjects completed 5-day diaries at the end of treatment and washout periods. The primary endpoint was change from baseline to week 4 in mean voided volume (MVV) per micturition. The primary comparison was standard-dose pregabalin/tolterodine ER versus tolterodine ER alone; secondary comparisons were pregabalin alone versus tolterodine ER alone and versus placebo., Results: Baseline-adjusted changes in MVV were significantly greater after treatment with standard-dose pregabalin/tolterodine ER (39.5 ml) versus tolterodine ER alone (15.5 ml; P<0.0001), and with pregabalin alone (27.4 ml) versus tolterodine ER alone (P=0.005) and placebo (11.9 ml; P=0.0006). Treatments were generally well tolerated; discontinuation rates due to adverse events were 4%, 2%, 5%, 0%, and 1% with standard- and low-dose pregabalin/tolterodine ER, pregabalin, tolterodine ER, and placebo, respectively., Conclusions: Pregabalin, alone or with tolterodine ER may offer an alternative treatment option for idiopathic OAB in women., (Copyright © 2010 Wiley-Liss, Inc.)

Unlabelled: INTRODUCTION & HYPOTHESIS: Determine if treatment of urge incontinence with tolterodine results in changes in bladder and/or urethral sensation using Current Perception Threshold (CPT) testing., Methods: Women with >or=1 incontinence episode on 7-day diary were treated with 4 mg of long-acting tolterodine for 2-months. At baseline and 2-months, participants had CPT testing of the urethral and bladder at 3 frequencies 2000, 250, and 5 Hz. Baseline and post-treatment measures were compared using Wilcoxon Signed Rank Test., Results: Seventeen women underwent baseline CPT testing. Four discontinued medication due to side effects and did not have repeated testing. Urethral CPT at 250 Hz was lower after treatment (median 1.3 [Interquartile range .69-2.1] and .75 [.45-1.2], p = .003) and at 5 Hz trended toward a significant decrease (1.1 [1-1.9] and .84 [.32-1.1], p = .06)., Conclusions: Urethral sensitivity improves after 2-months of tolterodine, suggesting it may restore urethral sensory nerves in addition to known motor effects., ((c) 2009 Wiley-Liss, Inc.)

Aims: To investigate whether vaginal estrogen cream combined with tolterodine is more effective than tolterodine alone in the treatment of postmenopausal women with overactive bladder (OAB)., Materials and Methods: This is an unblinded study without placebo. A preliminary study consisted of tolterodine 2 mg twice per day for 3 months had been conducted for 25 postmenopausal women with OAB. Over a period of 11 months, 80 postmenopausal women with OAB underwent a prospective randomized trial. These patients were equally randomized into two groups. The interventions for the 12-week treatment period included 2 mg tolterodine twice per day for the group A and 2 mg tolterodine twice per day/vaginal conjugated equine estrogen 0.625 mg twice a week for the group B. Identical pre- and post-treatment assessments included bladder diary, Urogenital Distress Inventory-6 (UDI-6), and Incontinence Impact Questionnaire-7 (IIQ-7)., Results: All 80 women (65.2 years, range 58-73) completed this study. The between groups comparison showed that the group B had significant improvements in mean daytime frequency and voided volume after treatment (14.8-5.8 vs. 14.1-6.4, P = 0.001 and 115.8-141.9 vs. 108.5-134.5, P = 0.007, respectively). Additionally, a comparison of the final total scores of UDI-6 and IIQ-7 between the two groups revealed that the group B had a statistically significant improvement in quality of life than that in the group A (8.6-6.9 vs. 9.5-7.2, P < 0.001 and 9.4-6.1 vs. 10.2-6.5, P < 0.001, respectively). Changes in the other symptoms, including nocturia, urgency and urge incontinence, were not statistically significant but actually achieved improved in both groups., Conclusions: A combination of vaginal estrogen cream and tolterodine is a potential therapy for postmenopausal women with OAB., ((c) 2008 Wiley-Liss, Inc.)

Aims: Studies have shown cognitive problems in adults treated with anticholinergics. It is unclear if children are also susceptible to anticholinergic adverse effects. This study evaluates the effects of long-acting oxybutynin and tolterodine on short-term memory and attention in children with urgency and urge incontinence., Methods: Children with urgency or urge incontinence were recruited to take part in a prospective, randomized double-blinded placebo controlled trial using long-acting oxybutynin or tolterodine. Patients underwent a baseline test of their memory/recall ability and attention span using a standardized developmental/neuropsychological assessment tool. They were then randomized to either medication or placebo with retesting in 2 weeks, at which time they were crossed. They were retested after the second 2 weeks., Results: Fourteen children (9 boys and 5 girls), ranging in age from 5 to 11 (M = 7.7) participated in the study. Attention and memory scores increased over time in all children, however, the analyses showed no significant negative effects of anticholinergic medications on attention or memory. Indeed, though not statistically significant, trends were for improvement in test scores in both areas., Conclusions: Our results in a double blinded cross-over trial suggest that long-acting oxybutynin and tolterodine do not have a deleterious effect on children's attention and memory. Other cognitive functions may be affected., ((c) 2007 Wiley-Liss, Inc)

Introduction and Objectives: The dosage of the antimuscarinic drugs: Tolterodine ER or Trospium was increased to a higher-than-recommended dosage in patients where the manufacturer's recommended dosage had failed. All patients were suffering from neurogenic detrusor overactivity incontinence. Tolerability and success were evaluated in the present study., Materials and Methods: Twenty-one patients with neurogenic detrusor overactivity were evaluated: 17 with spinal cord injury, 3 with multiple sclerosis, and 1 with a meningomyelocele. All patients catheterized themselves or were catheterized. If neurogenic detrusor overactivity continued and the medication was well tolerated, the dosage was doubled to either 8 mg of Tolterodine ER [2 x 4 mg (n = 11)] or 90 mg of Trospium [3 x 30 mg (n = 10)]. The follow-up was monitored by a bladder diary and urodynamic evaluation., Results: Sixteen patients significantly decreased their incontinence episodes from 8-12 episodes before to 0-2 episodes during the doubled treatment. The reflex volume increased from 202 +/- 68 to 332 +/- 50 ml (P < 0.001). Cystometric capacity enlarged from 290 +/- 56 to 453 +/- 63 ml (P < 0.001). One patient had to stop the medication because of intolerable side effects and five patients did not experience satisfactory benefit., Conclusion: The increased dosage of Tolterodine or Trospium is an effective treatment in patients with neurogenic bladder.

Aims: To determine whether women with urinary incontinence (UI) can identify their allocation in a randomized controlled trial (RCT) of tolterodine (TOL), and whether correct identification is associated with outcomes and adverse effects (AEs)., Methods: Exploratory analysis of a randomized, double-blind, placebo (PLC)-controlled trial of TOL 4 mg daily for 8 weeks in 743 women with urge-predominant mixed UI. Patient perception of their randomization was assessed at trial end. Main outcome measures were 7-day bladder diaries, patient perception of improvement, and UI-specific quality of life (QoL)., Results: TOL produced a significant decrease in urge UI episodes compared to PLC (78% vs. 51%, P = 0.0001). Fifty-one percent of women correctly identified their randomization (58% on TOL vs. 37% on PLC, P < 0.001). Women who assumed they took TOL had better bladder diary outcomes than those who assumed they took PLC. Within each assumption group, patient perception outcomes were similar, regardless of actual randomization. QoL improved in all domains except general health for women on TOL. In women who assumed they took TOL, significant drug benefit was evident in three domains. Moderate-severe dry mouth was higher in those who assumed they took TOL (7.3% vs. 0%, P < 0.0001)., Conclusions: Greater than fifty percent of women in this RCT of antimuscarinic treatment were "unblinded" to their randomization. Patient assumption of randomization was associated with bladder diary and perception outcomes, specific QoL domains, and dry mouth. Efficacy of urge incontinence drugs should be considered in the context of patient assumptions, expectations, and "unblinding" by easily evident side effects.

Objectives: To investigate whether the combination of tolterodine plus (Tp) a simple pelvic floor muscle exercise (PFME) program would provide improved treatment benefits compared with tolterodine alone (Ta) in patients with symptoms of overactive bladder (OAB)., Methods: After a 1-2 week run-in period, 480 patients with symptoms of urinary frequency (> or =8 micturitions/24 hr), urgency, and urge incontinence (> or =1 episode/24 hr), were randomized to receive tolterodine 2 mg bid with or without a simple PFME program for 24 weeks in this multinational study. Treatment efficacy was assessed by comparing the change from baseline in 3-day micturition diary recordings., Results: After 24 weeks' treatment, in the Ta group the urgency episodes reduced from mean of 4.1 to 1.5 (83% reduction) while in the Tp group the urgency episodes reduced from 4.2 to 2.1 (78.7% reduction). Mean incontinence episodes per day decreased from 3.21 (standard deviation (SD) 3.4) to 0.95 (SD 1.9) in Ta group and from 3.44 (SD 3.4) to 1.25 (SD 2.7) in the Tp group. Similarly, the number of micturition/24 hr were significantly reduced, from 12.78 to 9.20 (27.3% reduction) in the Ta group and from 11.87 to 9.29 (23% reduction) in the Tp group. There was an improvement in the patients' perception of urinary symptoms in 85.9% of patients on Ta and 81.7% patients on Tp PFME. There were no statistically significant differences between the groups with regard to any of the outcome parameters., Conclusions: Tolterodine therapy for 24 weeks results in significant improvement in urgency, frequency, and incontinence, however, no additional benefit was demonstrated for a simple PFME program., (Copyright 2003 Wiley-Liss, Inc.)

Tolterodine is a potent antimuscarinic agent specifically developed for the treatment of urinary urge incontinence and other symptoms related to the overactive bladder. In order to assess the optimum dosage for use in future clinical studies, a double-blind, randomized, placebo-controlled, parallel-group, multicenter study was performed in 90 patients with detrusor hyperreflexia and symptoms of urinary urgency, frequency, and/or urge incontinence. Urodynamic variables, micturition diary variables, and subjective urinary symptoms were measured before and after 2 weeks' treatment with either placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily (bd). Serum drug concentrations, electrocardiogram recordings, blood pressure, and incidence of adverse events were also assessed. Linear regression analysis showed a significant dose-response relationship for several clinically relevant urodynamic variables, while there was a trend towards an improvement in micturition diary variables and subjective assessment of symptoms with increasing dosages of tolterodine. There were no safety or tolerability concerns regarding any of the dosages of tolterodine investigated, although 2 patients treated with a dosage of 4 mg bd experienced urinary retention that necessitated dosage reduction. The results of this study suggest that tolterodine is well-tolerated and exerts a dose-dependent effect on bladder function in patients with detrusor hyperreflexia. The optimum dosage of tolterodine for use in future studies is 1-2 mg bd.

Tolterodine, a novel compound intended for treatment of urgency and urge incontinence, has been characterized as a potent muscarinic receptor antagonist in pharmacological in vitro and in vivo studies. In cats, tolerodine was shown to reduce bladder pressure at doses significantly lower than those affecting salivation. To predict clinical effectiveness, an open pilot study was performed in healthy male volunteers. Efficacy was measured by cystometry and by spontaneously reported effects after administration of a single oral dose of tolterodine, 6.4 mg, given as a water solution. Tolterodine had distinct inhibitory effects on urinary bladder function, both at 1 and 5 hours post-dose. At 1 hour, but not at 5 hours post-dose tolterodine also significantly reduced stimulated salvation. In addition to the objectively demonstrated changes in urodynamic parameters, most volunteers experienced voiding difficulties. No significant changes in blood pressure, heart rate, or near point of accommodation were registered. Tolterodine, in the dosage used, was both objectively and subjectively shown to exert a marked inhibitory effect on micturition in healthy subjects, and the data suggest a more pronounced effect on bladder function than on salivation.