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Effects on sleep of anticholinergics used for overactive bladder treatment in healthy volunteers aged > or = 50 years.

Diefenbach K, Arold G, Wollny A, Schwantes U, Haselmann J, Roots I.

Institut fur Klinische Pharmakologie, Charite- Universitatsmedizin Berlin, Campus Charite Mitte, Schumannstr. 20/21, D-10098 Berlin, Germany. ivar.roots charite.de

OBJECTIVE: To study the influence of oxybutynin, tolterodine or trospium chloride, anticholinergics used to treat bladder overactivity, on sleep and the cognitive skills of healthy volunteers aged > or = 50 years. SUBJECTS AND METHODS: In a randomized, double-blind, placebo-controlled study with a crossover design, 24 healthy sleepers (12 men and 12 women) aged 51-65 years underwent polysomnographic recordings and cognitive tests in a sleep laboratory. Study medications were given as a single dose containing the total recommended daily dose. RESULTS: There was a significant reduction in rapid-eye movement (REM) sleep of approximately 15% and a slightly (but not significantly) greater REM latency after oxybutynin and tolterodine than with placebo. After trospium chloride, REM duration and latency were comparable with placebo. There was no effect of the tested anticholinergics on cognitive and subjective sleep variables. CONCLUSION: Individuals aged > or = 50 years had a more distinct impairment of REM sleep after oxybutynin and tolterodine than had young people, but the reduction in REM sleep did not reach a pathological degree in this single-dose study. There was no apparent impairment of concentration or cognitive function, but impairment of cognitive function and neuropsychological side-effects cannot be excluded, especially when elderly patients with impaired REM sleep from various psychiatric diseases (e.g. depression) and/or sleep disturbances are given oxybutynin or tolterodine in long-term treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15679791&dopt=Abstract tolterodine Detrol



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Should we switch over to tolterodine in every child with non-neurogenic daytime urinary incontinence in whom oxybutynin failed?

Yucel S, Akkaya E, Guntekin E, Kukul E, Danisman A, Akman S, Baykara M.

Section of Pediatric Urology, Akdeniz University School of Medicine, Antalya, Turkey. syucel akdeniz.edu.tr

OBJECTIVES: To assess the clinical efficacy of tolterodine prescribed to children with non-neurogenic daytime urinary incontinence secondary to overactive bladder who had previously failed to improve with oral oxybutynin treatment and its relation to the side-effect profile and compliance status. METHODS: We evaluated 92 children presenting with daytime wetting, with or without nocturnal enuresis, who were receiving oral oxybutynin treatment. Children with chronic urinary tract infections, a neurologic lesion, an anatomic abnormality of lower urinary tract, voiding abnormality, and less than 1 year of oxybutynin treatment were excluded. Of the remaining 41 children (mean age 7.2 years, range 5 to 14 years), 30 agreed to switch to tolterodine and 11 continued receiving oxybutynin. Anticholinergic side effects, compliance, and clinical efficacy were assessed in the follow-up. RESULTS: Of the 30 patients who switched to tolterodine, a complete response was in 18 patients (60%), partial improvement in 11 (37%), and no improvement in 1 (3%) after a mean of 14.4 months (range 12 to 16 months) of oxybutynin treatment. The anticholinergic side-effect score was 7.2, 9.3, and 11, respectively, for those with a complete response, partial improvement, and no improvement in the compliant group. The noncompliant group had the greatest side-effect score (16.9). The fairly compliant group had a side-effect score of 12.3. After a mean of 7.1 months (range 6 to 9 months) of tolterodine use, a complete response was reported in 24 patients and partial improvement in 5 (17%). In 1 patient, treatment failed completely. However, his side-effect score decreased from 11 to 2. All tolterodine users were compliant with treatment. CONCLUSIONS: The results of this study in children with non-neurogenic daytime urinary incontinence have shown that tolterodine may increase the efficacy of pharmacotherapy, particularly in patients noncompliant to oxybutynin. Additional investigation of the anticholinergic side-effect scores and compliance tables is required to improve the clinical results of pharmacotherapy in incontinence due to overactive bladder in children.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15708055&dopt=Abstract tolterodine Detrol



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TOLTERODINE TREATMENT FOR CHILDREN WITH SYMPTOMS OF URINARY URGE INCONTINENCE SUGGESTIVE OF DETRUSOR OVERACTIVITY: RESULTS FROM 2 RANDOMIZED, PLACEBO CONTROLLED TRIALS.

Nijman RJ, Borgstein NG, Ellsworth P, Djurhuus JC.

From the Department of Urology, Groningen University Hospital, Groningen, The Netherlands (RJMN), Pfizer Worldwide Research, New London, Connecticut (NGB), Division of Urology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts (PE), and Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark (JCD).

PURPOSE:: We report the results of the first 2 large randomized controlled trials designed to evaluate the efficacy and safety of tolterodine extended release in children 5 to 10 years old with symptoms of urinary urge incontinence suggestive of detrusor overactivity. MATERIALS AND METHODS:: Two double-blind, placebo controlled trials were conducted sequentially. Children 5 to 10 years old with incontinence suggestive of detrusor overactivity (1 or more diurnal incontinence episodes per 24 hours) were randomized to tolterodine (2 mg daily) or placebo for 12 weeks. The primary end point was the change from baseline to week 12 in the number of incontinence episodes per week. Changes from baseline in the number of voids per 24 hours and volume of urine per void were also evaluated. Exploratory analyses were conducted to determine whether particular subsets of patients showed differential responses to treatment. RESULTS:: A total of 224 and 487 children (mean age 8 years) were randomized to placebo and tolterodine, respectively. Differences in the number of incontinence episodes per week, voids per 24 hours, and volume of urine per void between tolterodine and placebo did not reach statistical significance. This finding may be explained by a high placebo response and under dosage of tolterodine among children with greater body weight. Tolterodine was well tolerated. CONCLUSIONS:: Analysis of the primary efficacy outcome did not reveal a statistically significant effect of treatment. However, secondary analyses demonstrated that tolterodine was well tolerated among 5 to 10-year-old children with diurnal incontinence. Exploratory analyses also showed that children weighing 35 kg or less with detrusor overactivity characterized by incontinence and/or frequent voiding benefited most from tolterodine treatment, suggesting that a weight adjusted dosing regimen may be required for optimal response among older and heavier children.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15758796&dopt=Abstract tolterodine Detrol



Detrol
Urodynamic and other effects of tolterodine: a novel antimuscarinic drug for the treatment of detrusor overactivity.

Stahl MM, Ekstrom B, Sparf B, Mattiasson A, Andersson KE.

Department of Clinical Pharmacology, Lund University Hospital, Sweden.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8750383&dopt=Abstract tolterodine Detrol