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PubMed2005

Treatment of overactive bladder (OBA) with anti-cholinergic drugs and the risk of glaucoma.

Overactive bladder (OAB) and glaucoma are prevalent and frequently co-exist, particularly in the elderly. Anti-cholinergic drugs are the cornerstone of medical management of OAB. There is a great deal of confusion about the safety of use of the anti-cholinergic medication regarding the risk of glaucoma. This review examines the pharmacological relationship of anti-cholinergic medications used to treat OAB and the various types of glaucoma.

Adult↗
PubMed2005

Brain control of normal and overactive bladder.

PURPOSE: Bladder control problems are common but their cause is often unclear. Many investigators have sought causes in the lower urinary tract, but fewer in the supraspinal control system. We have used functional magnetic resonance imaging (fMRI) to determine brain responses to bladder filling in subjects with normal and with poor bladder control (detrusor overactivity). MATERIALS AND METHODS: Cerebral responses to bladder infusion were recorded in 1 male and 11 females without overt neurological abnormality, aged 26 to 83 years. Six had good bladder control and 6 had poor control on prior urodynamics. fMRI was performed while repeatedly infusing and withdrawing liquid into and out of the bladder, and monitoring intravesical pressure. Measurements were made at small and large bladder volumes. RESULTS: fMRI detected activation of many brain regions involved in bladder control, including periaqueductal gray, thalamus, insula, dorsal anterior cingulate, and ventromedial cerebellum. Orbitofrontal cortex, pontine micturition center and preoptic hypothalamus were visible in subgroup analyses. Activations outweighed deactivations and responses became stronger at large bladder volumes. Among subjects with good control, this strengthening of response was prominent in the orbitofrontal cortex. Among those with poor control cortical responses were exaggerated at larger bladder volumes, except in the orbitofrontal cortex, which remained weakly activated. This difference was not due to concurrent detrusor activity. CONCLUSIONS: Poor bladder control is specifically associated with inadequate activation of orbitofrontal cortex. Clinically, frontal cortical lesions cause bladder control problems. This study suggests a similar neurophysiological basis for poor bladder control in the absence of overt neurological lesion.

Adult↗
PubMed2004

Impact of a health education intervention in overactive bladder patients.

OBJECTIVE: To assess a standardized and simple educational intervention in overactive bladder (OAB) patients to improve compliance with anticholinergic medication, increase the use of concomitant behavioral treatments, and improve patients' perception of bladder symptoms. MATERIALS AND METHODS: This is a 16-week open-label randomized trial of tolterodine combined with an education intervention for the experimental group versus tolterodine alone (no intervention) for the control group. The setting was in family medicine and urology clinics in Ontario. The participants were male and female adults with OAB symptoms. Both groups received tolterodine prescriptions. The intervention patients received printed information and an explanation about OAB, medication use, and behavioral treatments (kegel exercise, bladder stretching, fluid regulation). The primary outcomes were medication compliance and persistence at 16 weeks. Secondary outcomes were use of behavioral treatments and self-reported severity of symptoms. RESULTS: More patients in the intervention group (experimental) purchased their prescriptions (p<0.05). Compliance rate was greater for the intervention group (39%), versus the control group (31%) at 16 weeks although the difference was not significant (p>0.05). Significantly more patients started and/or continued non-drug treatments in the intervention group (82%) compared to the control group (53%) (p<0.05). Furthermore, more patients in this group reported improvement in severity of bladder symptoms (p<0.05). CONCLUSIONS: The simple education intervention resulted in a greater, but not significant, increase in compliance with medication compared to the control group. It also resulted in a significantly increased use of behavior modification therapies and better self-perception of treatment outcome.

Aged↗
PubMed2005

Recent developments in the management of overactive bladder: focus on the efficacy and tolerability of once daily solifenacin succinate 5 mg.

BACKGROUND: Overactive bladder (OAB) is a highly prevalent symptom complex that may be extremely distressing to the patient, and can be associated with co-morbidities and reduced quality of life (QoL). One of the major pathophysiological causes of OAB is overactivity of the detrusor muscle, mediated via muscarinic receptors in the bladder. Urgency is the defining symptom of OAB, yet a significant proportion of patients also suffer from incontinence, which is the most distressing symptom to the patient. As such, restoration of continence should be a primary treatment goal. However, effective treatments should also impact on the other key symptoms of OAB, such as micturition frequency and urgency. Non-pharmacologic interventions to treat OAB can be effective but require patients to be highly motivated. In terms of pharmacologic therapy, treatment with an antimuscarinic agent is the mainstay of current therapy. Solifenacin succinate is a once-daily oral antimuscarinic for the treatment of OAB. The recommended dose is 5mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. OBJECTIVES: This paper reviews clinical experience with solifenacin 5 mg in patients with OAB as this is the recommended dose according to FDA product labeling. FINDINGS: In Phase 3 studies, based on data captured in 3-day micturition diaries, greater than half of patients who were incontinent at baseline no longer reported experiencing incontinence episodes after 12 weeks of double-blind treatment with solifenacin 5 mg. Furthermore, compared with placebo, solifenacin treatment resulted in statistically significant reductions in incontinence episodes, micturition frequency and urgency episodes, with significant increases in volume voided (based on an analysis of key symptom outcomes in two pooled Phase 3 studies presented here). The most common treatment-related adverse events were expected anticholinergic side effects (dry mouth, constipation, and blurred vision), and these were generally mild to moderate. Discontinuation rates due to adverse events in the treatment and placebo groups were comparable. CONCLUSION: Solifenacin 5 mg was found to be efficacious and had an acceptable tolerability profile in patients with OAB in these trials and this treatment may provide QoL benefits to patients.

Administration, Oral↗
PubMed2004

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.

Aged↗
PubMed2004

Prevalence of overactive bladder in Asian men: an epidemiological survey.

OBJECTIVE: To study the epidemiology of overactive bladder (OAB) and the influence of demographic factors on its incidence in Asian men. SUBJECTS AND METHODS: A survey based on a self-administered questionnaire (locally translated in participating countries) was conducted between March 1998 and May 1998 to quantify the prevalence of OAB in a random sample of men (2369, aged 18-70+ years) visiting other than urology clinics in 26 centres in 11 Asian countries. The questionnaire was divided into two parts, i.e. social and demographic factors, and OAB symptoms. For OAB the questionnaire primarily focused on symptoms, degree of bother and treatment measures. The degree of bother was quantified by classifying it as mild, moderate and severe. The statistical relationship between demographics and OAB was assessed using the chi-square independent test. RESULTS: The prevalence of OAB was 29.9% (709 men); OAB was more common in professional workers (43%), the high-income group (26%, income of > US$ 800) and urban dwellers (64%). With increasing age the incidence of OAB increased, i.e. the prevalence was 53% in men aged > 70 years; the family history and type of toilets used had some relationship with OAB. Frequency (37%), urgency (34%), and frequency and urgency (10%) were the most common symptoms of OAB. Urge incontinence symptoms were reported by 13%. Some degree of bother was recorded in 32% of those with OAB, of whom only 5.9% received treatment for their OAB, with general practitioners and specialists being preferred equally. CONCLUSIONS: The prevalence of OAB in Asian men is high and more common in older patients. The treatment rate for the symptoms was much lower than in western countries, suggesting a need for better education of patients and more research for effectively managing the OAB.

Adolescent↗
PubMed2005

Health-related consequences of overactive bladder: an economic perspective.

About 34 million people in the USA have an overactive bladder (OAB), a condition characterized by urinary urgency, with or without urinary incontinence, and usually frequency and nocturia. This condition is associated with increased health risks (e.g. urinary tract infection, falls and fall-related injuries, including broken bones), as well as admission to nursing homes and prolonged hospital stays. The annual costs associated with OAB in the community setting are >9 billion dollars, including 2.9 billion dollars for diagnosis and treatment, 1.5 billion dollars for routine care, 3.9 billion dollars for treatment of health-related consequences, and 841 million dollars in lost productivity. These cost patterns raise the possibility that treating OAB at an early stage may both improve patient care and minimize overall use of healthcare resources. However, before a thorough economic analysis of OAB can be undertaken, more data are needed about the long-term costs and the pathogenesis of OAB-related conditions.

Adult↗
PubMed2002

Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of overactive bladder (OAB) patients foilowing treatment with tolterodine extended-release (ER) 4 mg once daily versus placebo. STUDY DESIGN: Multinational, placebo-controlled, randomized, double-blind 12-week study. POPULATION: Patients with urinary frequency ( > or = 8 micturitions/24 hours over a 7-day period), urge incontinence ( > or = 5 episodes/week), and symptoms of OAB for at least 6 months were eligible for inclusion. Patients (81% female) received oral therapy with tolterodine ER (n = 507) or placebo (n = 508) for 12 weeks. OUTCOMES MEASURED: HRQoL was assessed using the King's Health Questionnaire (KHQ) and Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Patients also rated their bladder condition. Assessments were performed at baseline and at the end of treatment. RESULTS: At end of treatment, KHQ domains selected a priori as primary HRQoL end points (incontinence impact and role limitations) significantly improved (P < or = .001) with tolterodine ER. Domains selected a priori as secondary end points (physical limitations, sleep and energy, severity [coping] measures, and symptom severity) were also significantly improved (P < or = .006) following treatment with tolterodine ER. The tolterodine ER group had decreased symptom severity and statistically significant improvements in patient rating of bladder control compared with the placebo group at end of treatment. No treatment differences were detected using the SF-36. CONCLUSION: Many aspects of HRQoL, as measured by the KHQ, showed statistically significant improvement following treatment with tolterodine ER. These HRQoL improvements were consistent with clinical efficacy benefits. Patients receiving tolterodine ER experienced overall improvement in their condition that was associated with an important impact on their HRQoL.

Aged↗
PubMed2003

Transdermal systems for overactive bladder: principles and practice.

The transdermal system for delivery of medication to treat overactive bladder may provide an improved efficacy-to-tolerability ratio by regulating serum drug levels; avoiding gastrointestinal and hepatic metabolism, which is important when the metabolite has a lesser therapeutic index than the parent drug; and achieving clinical efficacy with a lower total drug burden. Additional advantages may include increased compliance and obviation of the need for oral drug administration, which is especially beneficial for the patient who is taking multiple oral medications or is caregiver-dependent. An efficient patch system must preserve the physical integrity of the drug layer, provide adequate adhesion, store and release the drug and permeation-enhancing agent in a predictable manner, promote consistent absorption through the skin regardless of location or skin or subcutaneous tissue differences, demonstrate dose proportionality, maintain skin integrity during product use and removal, and be cosmetically acceptable. A novel transdermal delivery system that incorporates an occlusive layer covering an acrylic adhesive containing the active agent oxybutynin and a skin permeation enhancer has been demonstrated in clinical trials to achieve these goals.

Journal Article↗
PubMed2002

Selecting a medical therapy for overactive bladder.

Immediate-release oxybutynin was the gold standard for pharmacologic treatment of overactive bladder for nearly 30 years. Intolerable systemic side effects, in particular dry mouth, limited its clinical utility, resulting in poor patient compliance with dosing regimens. Multiple studies have demonstrated the vastly superior tolerability of tolterodine, extended-release tolterodine, and extended-release oxybutynin over that of immediate-release oxybutynin at equivalent doses, and in the case of extended-release oxybutynin even to twice the dose of the original immediate-release form. With different drug delivery systems and, perhaps, with better bladder selectivity, these new oral agents have favorable side effect profiles, which translate into higher patient compliance and fewer treatment withdrawals or dosage reductions.

Journal Article↗
PubMed2002

Treatment of overactive bladder and incontinence in the elderly.

The prevalence of urinary incontinence (UI) and overactive bladder rises with age, and elderly people are the fastest-growing segment of the population. Many elderly people assume UI is a normal part of the aging process and do not report it to their doctors, who must therefore make the effort to elicit the information from them. Coexisting medical problems in older patients and the multiple medications many of them take make diagnosis and treatment more complex in this population. Just as the etiology of incontinence is often multifactorial, the treatment approach may need to be multipronged, with behavioral, environmental, and medical components; in any case, it must be targeted to the individual patient. New, less-invasive surgical techniques and devices make surgery more feasible if other therapy fails.

Journal Article↗
PubMed2006

Symptom change in women with overactive bladder after extracorporeal magnetic stimulation: a prospective trial.

The purpose of this study was to prospectively evaluate symptom change after discontinuation of extracorporeal magnetic stimulation (EMS) in women with overactive bladder (OAB). A total of 48 women with OAB were included. We applied 10 Hz of repetitive magnetic stimulation with a "magnetic chair" for 20 min, twice weekly for 8 weeks. Changes in OAB symptoms at 2, 12, and 24 weeks after discontinuing the EMS were evaluated. Twenty-seven (56.3%) patients were cured compared with the baseline at 2 weeks: the cure rate was determined as 68.8% (33/48 patients), 56.3% (27/48), and 50% (8/16) for urgency, frequency, and urge incontinence, respectively. The mean number of voids per 24 h was decreased by 42.8% (from 14.5 +/- 4.3, to 8.3 +/- 1.5, P < 0.001) at 2 weeks after treatment. Maximum voided volume did not change significantly, but the mean voided volume increased significantly after stimulation. Twenty-six (96.3%) patients among the 27 patients who achieved a cure at 2 weeks, maintained improvement at 24 weeks; the therapeutic effect on urgency, frequency, and urge incontinence persisted in 26 (78.8%) of 33 patients, 26 (96.3%) of 27 patients, and six (75%) of eight patients, respectively. There were no significant changes in urodynamic parameters. Of the 14 patients with detrusor overactivity, the condition was no longer observed in four (28.6%) patients. EMS has a beneficial effect on women with OAB. Our data suggest EMS may have a significant carry-over effect in well-selected OAB patients.

Adolescent↗
PubMed2004

Mechanisms involved in new therapies for overactive bladder.

During the last few years, vanilloid substances and botulinum-A toxin were extensively investigated as new therapies for overactive bladder. Intravesical administration of capsaicin or resiniferatoxin--2 members of the vanilloid family--has been shown to increase bladder capacity and decrease urge incontinence in patients with neurogenic, as well as nonneurogenic, forms of detrusor overactivity. In addition, vanilloids have been shown also to reduce bladder pain in patients with hypersensitive disorders. Vanilloids are exogenous ligands of vanilloid receptor type 1 (VR1), an ion channel present in the membrane of type C primary afferent nerve fibers. This receptor, which plays a key role in pain perception and control of the micturition reflex, may be upregulated by nerve growth factor (NGF), a neurotrophic molecule detected in high concentrations in overactive detrusor tissue. Vanilloids, by reducing uptake of NGF through sensory neurons, may counteract VR1 upregulation. Intravesical injections of botulinum-A toxin, a neurotoxin produced by Clostridium botulinum, were shown to increase bladder capacity and to decrease urge incontinence episodes in patients with neurogenic detrusor overactivity. Botulinum-A toxin impedes the release of acetylcholine from cholinergic nerve endings at the neuromuscular junction, leading to paralysis of the detrusor smooth muscle.

Animals↗
PubMed2005

Overactive bladder syndrome: considerations in pharmacotherapy and new perspectives.

The great epidemiological relevance of the overactive bladder (OAB) syndrome and its impact on quality of life of sufferers has encouraged a growing amount of research both in basic science and in clinical fields, with the pharmacological treatment of OAB syndrome being particularly investigated. Recently a new perspective for the use of alpha-lytic drugs in the treatment of OAB syndrome has been disclosed due to encouraging anecdotal data, and to the identification of different adrenoceptor subtypes in the female lower urinary tract. Starting with a reference picture of female lower urinary tract disorders, the authors review the present pharmacological treatment of female lower urinary tract disorders, and delineate the new perspectives acquired from recent studies of adrenoceptor subtypes.

Adrenergic alpha-Antagonists↗
PubMed2004

New pharmacologic targets for the treatment of the overactive bladder: an update.

Although currently available antimuscarinic agents are the standard of care for overactive bladder (OAB), they are limited by certain side effects, particularly dry mouth and constipation. Research aimed at discovering new therapies for OAB has resulted in the identification of some promising drugs. Investigations of pharmacologic targets in the central nervous system (CNS) have yielded encouraging results with several agents, including tramadol and gabapentin. Further investigation may show that drugs acting at serotonergic and noradrenergic CNS sites are clinically useful as therapies for OAB. Some peripherally acting drugs, such as resiniferatoxin and botulinum toxin, have already been proved to be of clinical value. However, development of other agents that block afferent or efferent nerve impulses in the bladder through activity at vanilloid, purinergic, or opioid-like receptor sites may result in clinically useful drugs.

Acetates↗
PubMed2002

Future studies of overactive bladder: the need for standardization.

Clinicians and researchers agree that pharmacologic studies of the overactive bladder (OAB) require precise planning, strict adherence to study design, and meticulous attention to study conduct and statistical methods. In addition, there should be straightforward and highly directed formulation of the conclusions derived expressly from data that have been collected. The exact methods to achieve these ends, however, are often debated among statisticians and experts in study design and by physicians who interpret the clinical implications of the findings. For these reasons, the conclusions of clinical research in OAB are commonly criticized on the basis of study objectives, study design, statistical methods, or conclusions. However, a subtler, but possibly more critical problem exists: the method of defining the population and the methods for collecting the data for the efficacy outcome parameters, including frequency, urgency, and urge incontinence.

Adult↗
PubMed2006

Overactive bladder syndrome: considerations in pharmacotherapy and new perspectives.

The important epidemiological relevance of the overactive bladder (OAB) syndrome and its impact on the quality of life of sufferers have increased research both in basic science and in clinical fields, with the pharmacological treatment of OAB syndrome being particularly investigated. Recently a new perspective for the use of alpha-adrenolytic drugs in the treatment of OAB syndrome has been gained due to encouraging anecdotal data and to the identification of different adrenoceptor subtypes in the female lower urinary tract. Starting with a survey of female lower urinary tract disorders, the authors review the present pharmacological treatment of these disorders and delineate the new perspectives acquired from recent studies of adrenoceptor subtypes.

Adrenergic alpha-Antagonists↗