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PubMed2006

The overactive bladder: review of current pharmacotherapy in adults. Part 1: pathophysiology and anticholinergic therapy.

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Administration, Cutaneous↗
PubMed2005

Botulinum toxin for the treatment of lower urinary tract symptoms: a review.

AIMS: To review the available literature on the application of botulinum toxin in the urinary tract, with particular reference to its use in treating detrusor overactivity (DO). METHODS: Botulinum toxin, overactive bladder (OAB), detrusor instability, DO, detrusor sphincter dyssynergia (DSD), and lower urinary tract dysfunction were used on Medline Services as a source of articles for the review process. RESULTS: DO poses a significant burden on patients and their quality of life. Traditionally patients have been treated with anti-cholinergic drugs if symptomatic, however, a significant number find this treatment either ineffective or intolerable due to side effects. Recent developments in this field have instigated new treatment options, including botulinum toxin, for patients' refractory to first line medication. Botulinum toxin, one of the most poisonous substances known to man, is a neurotoxin produced by the bacterium Clostridium botulinum. Botulinum toxin injections into the external urethral sphincter to treat detrusor sphincter dyssynergia has been successfully used for some years but recently its use has expanded to include voiding dysfunction. Intradetrusal injections of botulinum toxin into patients with detrusor overactivity and symptoms of the overactive bladder have resulted in significant increases in mean maximum cystometric capacity and detrusor compliance with a reduction in mean maximum detrusor pressures. Subjective and objective assessments in these patients has shown significant improvements that last for 9-12 months. Repeated injections have had the same sustained benefits. CONCLUSIONS: Application of botulinum toxin in the lower urinary tract has produced promising results in treating lower urinary tract dysfunction, which needs further evaluation with randomised, placebo-controlled trials.

Anti-Dyskinesia Agents↗
PubMedDate not supplied

Validation of an overactive bladder awareness tool for use in primary care settings.

Overactive bladder (OAB)--a syndrome characterized by urinary urgency, with or without urge incontinence, urinary frequency and nocturia--is estimated to affect 10% to 20% of the US and European populations. This study was carried out to validate a patient-administered screening awareness tool to identify patients with bothersome OAB symptoms. Patients were recruited from 12 primary care and 1 gynecology practice during regularly scheduled appointments. Enrollees completed an 8-item questionnaire assessing the amount of "bother" they associated with OAB symptoms. Clinicians then asked the patients 4 questions regarding urinary frequency, urgency, nocturia, and incontinence. If the screening was positive for symptoms of OAB or if the patient provided positive responses to the urinary symptom questions, the clinician asked additional questions regarding lifestyle and coping behaviors. The clinician then diagnosed the patient, placing him or her in the "No OAB," "Possible OAB," or "Probable OAB" category. Multivariable logistic regressions controlling for age and sex were performed to assess the applicability of the tool for identifying patients with OAB. A total of 1,299 patients were enrolled, and 1,260 provided complete data. Patients were aged 51.6+/-17.0 years, 62% were female, most (89%) were Caucasian, 22% experienced urinary urgency, and 18% experienced urge incontinence. The prevalence of Probable OAB was 12%. The c-index of the model identifying patients with a diagnosis of Probable OAB was 0.96, with a sensitivity and specificity of 98.0 and 82.7. For OAB-V8 scores >or=8, the odds ratio for Probable OAB was 95.7 (95% CI: 29.3; 312.4). The OAB-V8 performed well in helping clinicians identify patients with bothersome OAB symptoms in a primary care setting and will assist clinicians in identifying patients who may benefit from treatment.

Female↗
PubMed2006

Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis.

BACKGROUND: Overactive bladder (OAB) syndrome is characterized by urinary frequency and urgency with or without urge incontinence, and often accompanied by nocturia. The prevalence of OAB increases with aging; it is a particularly common condition among the elderly, affecting at least 25% of people aged > or = 65 years. OBJECTIVE: The goal of this study was to assess the efficacy and tolerability of solifenacin 5 and 10 mg once daily for treating elderly subjects with OAB. METHODS: This was a retrospective analysis of pooled data from 4 studies. Data were analyzed from elderly subjects (aged > or = 65 years) with OAB who were treated with solifenacin in four 12-week, double-blind, Phase III, international, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled studies and from elderly subjects who received solifenacin in a 40-week, open-label, flexible-dose extension trial that enrolled subjects who completed 2 of the double-blind studies. Micturition data were collected from diaries completed during the 3 days before each study visit. Efficacy end points included mean change from baseline for the number of incontinence episodes/24 hours, urgency episodes/24 hours, number of micturitions/24 hours, and volume voided/micturition. The proportion of subjects who became continent or had no urgency episodes at end point was also evaluated. RESULTS: The mean age of the subjects in the 12-week, double-blind studies (N = 1045; 781 women, 264 men) was 71.9 years; mean age in the 40-week extension trial (N = 509; 359 women, 150 men) was 71.2 years. The majority of subjects (74.7% in the 12-week, double-blind studies and 70.5% in the 40-week extension trial) were female, and >90% of the elderly subjects were white. The duration of OAB ranged from 0 to 66 months, and 43.7% had received previous medical therapy for OAB. The completion rate for elderly subjects was 85.5% for the 12-week, double-blind studies and 80.0% for the 40-week extension trial. Efficacy end points at week 12 of double-blind treatment demonstrated statistically significant improvements in the symptoms of OAB with solifenacin compared with placebo. Mean (SE) changes in number of incontinence episodes/24 hours were -1.5 (0.17) for the 5-mg dose and -1.9 (0.14) for the 10-mg dose compared with -1.0 (0.14) for placebo (P = 0.013 for the 5-mg dose and P < 0.001 for the 10-mg dose, vs placebo); mean (SE) changes in the number of urgency episodes/24 hours were -3.2 (0.27) for the 5-mg dose and -3.2 (0.19) for the 10-mg dose compared with -1.6 (0.18) for placebo (P < 0.001 for both doses vs placebo); mean (SE) changes in the number of micturitions/24 hours were -2.0 (0.17) for the 5-mg dose and -2.5 (0.13) for the 10-mg dose compared with -1.1 (0.13) for placebo (P < 0.001 for both doses vs placebo); mean (SE) changes in the volume voided/micturition were 30.2 (3.24) mL for the 5-mg dose and 46.2 (2.55) mL for the 10-mg dose, compared with 9.1 (2.39) mL for placebo (P < 0.001 for both doses vs placebo). The proportion of subjects with restoration of continence was 49.1% and 47.3% of the 5- and 10-mg treatment groups, respectively, compared with 28.9% of the placebo group (P < 0.001 for both doses vs placebo). The proportion of subjects with resolution of urgency was 34.6% and 24.9% for the 5- and 10-mg treatment groups, respectively, compared with 16.9% of the placebo group (P < 0.001 for the 5-mg dose and P < 0.01 for the 10-mg dose). Improvements in incontinence, urgency, and micturitions were maintained during the 40-week extension trial. The most common adverse events in both the double-blind and extension trials were dry mouth, constipation, and urinary tract infection. Most adverse events were mild to moderate in nature and did not result in treatment discontinuation. CONCLUSIONS: In these pooled analyses, solifenacin 5 and 10 mg once daily were efficacious and well tolerated in the treatment of these elderly subjects with OAB. Solifenacin therapy was also associated with a high level of persistence in a 40-week extension trial.

Aged↗
PubMed2005

Prognostic factors for successful percutaneous tibial nerve stimulation.

OBJECTIVE: In sacral as well as tibial nerve stimulation test stimulation is the main prognostic factor for success. In our study we tried to identify prognostic patient characteristics to improve patient selection for neuromodulation therapy. METHODS: PTNS was applied to 132 patients in 8 study centers (51 men, 81 women, mean age of 53 years (range: 21-82)). 83 patients were treated for overactive bladder, 16 for non-obstructive urinary retention and 33 for chronic pelvic pain. All patients had to fill out micturition or pain diaries, as well as quality of life questionnaires before and after treatment. Patient characteristics were evaluated for their prognostic value for successful outcome of neuromodulation therapy with use of logistic regression. RESULTS: Objective success was seen in 32.6% of patients, subjective success in 51.5%. Most evaluated clinical parameters proved not to be of prognostic value. A history of sexual and/or physical abuse was found in 12 of 103 interviewed patients, but did not alter PTNS treatment outcome. However, a low total score at baseline in the SF-36 questionnaire proved to be predictive for not obtaining objective (OR 0.444 [95% CI: 0.198-0.996], p = 0.04) or subjective success (OR 0.424 [CI: 0.203-0.887], p = 0.02). Especially patients with a low SF-36 Mental Component Summary were prone to fail neuromodulation therapy: OR 0.123 (95% CI: 0.273-0.552), p = 0.006 for objective success. These patients also scored worse on disease-specific quality of life questionnaires, although they had no different disease severity compared to patients with good mental health. CONCLUSION: Bad mental health as measured with the SF-36 Mental Component Summary does not depend on symptom severity and is a negative predictive factor for success of percutaneous tibial nerve stimulation. It therefore might be used as a tool for better patient selection in neuromodulation therapy.

Adult↗
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↗
PubMed2003

Clinical pharmacokinetics of drugs used to treat urge incontinence.

Urge incontinence (also known as overactive bladder) is a common form of urinary incontinence, occurring alone or as a component of mixed urinary incontinence, frequently together with stress incontinence. Because of the pathophysiology of urge incontinence, anticholinergic/antispasmodic agents form the cornerstone of therapy. Unfortunately, the pharmacological activity of these agents is not limited to the urinary tract, leading to systemic adverse effects that often promote nonadherence. Although the pharmacokinetics of flavoxate, propantheline, scopolamine, imipramine/desipramine, trospium chloride and propiverine are also reviewed here, only for oxybutynin and tolterodine are there adequate efficacy/tolerability data to support their use in urge incontinence. Oxybutynin is poorly absorbed orally (2-11% for the immediate-release tablet formulation). Controlled-release oral formulations significantly prolong the time to peak plasma concentration and reduce the degree of fluctuation around the average concentration. Significant absorption occurs after intravesical (bladder) and transdermal administration, although concentrations of the active N-desethyl metabolite are lower after transdermal compared with oral administration, possibly improving tolerability. Food has been found to significantly affect the absorption of one of the controlled-release formulations of oxybutynin, enhancing the rate of drug release. Oxybutynin is extensively metabolised, principally via N-demethylation mediated by the cytochrome P450 (CYP) 3A isozyme. The pharmacokinetics of tolterodine are dependent in large part on the pharmacogenomics of the CYP2D6 and 3A4 isozymes. In an unselected population, oral bioavailability of tolterodine ranges from 10% to 74% (mean 33%) whereas in CYP2D6 extensive metabolisers and poor metabolisers mean bioavailabilities are 26% and 91%, respectively. Tolterodine is metabolised via CYP2D6 to the active metabolite 5-hydroxymethyl-tolterodine and via CYP3A to N-dealkylated metabolites. Urinary excretion of parent compound plays a minor role in drug disposition. Drug effect is based upon the unbound concentration of the so-called 'active moiety' (sum of tolterodine + 5-hydroxymethyl-tolterodine). Terminal disposition half-lives of tolterodine and 5-hydroxymethyl-tolterodine (in CYP2D6 extensive metabolisers) are 2-3 and 3-4 hours, respectively. Coadministration of antacid essentially converts the extended-release formulation into an immediate-release formulation. Knowledge of the pharmacokinetics of these agents may improve the treatment of urge incontinence by allowing the identification of individuals at high risk for toxicity with 'usual' dosages. In addition, the use of alternative formulations (controlled-release oral, transdermal) may also facilitate adherence, not only by reducing the frequency of drug administration but also by enhancing tolerability by altering the proportions of parent compound and active metabolite in the blood.

Aging↗
PubMed2001

Overactive bladder: optimizing quality of care.

Overactive bladder (OAB), the symptom complex of urinary urgency and frequency with or without urge incontinence, affects the lives of millions of Americans. In recent years, more successful treatment options have emerged as advances have been made in understanding the pathophysiologic processes underlying OAB symptoms. However, because most therapeutic modalities for OAB are aimed at symptom resolution, rather than the treatment of distinct pathologic entities, a basic evaluation is required for all patients to establish whether existing (and treatable) pathologic processes are present. In the absence of these processes, symptom relief is both the objective and the outcome used to judge the efficacy of a specific modality. The type of therapy recommended for OAB may depend on several factors including age, existing behavioral patterns, estrogen status, degree of motivation, environmental surroundings, presence of other coexisting urinary symptoms, family support, and patient expectations. This article focuses on methods of identifying patients with OAB, and the role of developing strategies in treating this common disorder.

Aged↗
PubMed2005

Safety and tolerability of tolterodine for the treatment of overactive bladder in adults.

This article evaluates the safety and tolerability of tolterodine for the treatment of overactive bladder (OAB), which is defined as urinary urgency with or without urgency incontinence, usually with frequency and nocturia, but without infection or pathology. OAB affects tens of millions of people worldwide. Data are summarized from clinical trials and from postmarketing surveillance studies.

Adult↗
PubMed1995

[Disorders of bladder function in the elderly].

Voiding dysfunction in elderly patients is not a uniform disease entity. Diseases of the cerebrospinal system, metabolic imbalances, detrusor degeneration and bladder outlet obstruction or sphincter impairment can all result in disabilities such as urinary retention and/or urinary incontinence. Although the urodynamic pattern of an uninhibited neuropathic bladder resulting from a poorly functioning corticoreticular system may seem to be normal in these elderly subjects, many of them have lost control of the micturition reflex: the warning to void occurs suddenly at full bladder capacity, and the abrupt sensation that urination is imminent cannot be controlled appropriately. Classifying these symptoms under a simple common denominator, such a detrusor instability can be misleading, because the therapeutic approach in these patients should be more highly differentiate. Detrusor overactivity may be symptomatic and associated with curable diseases of the lower urinary tract, such as bladder outlet obstruction, urinary tract infection or bladder cancer. On the other hand, some of the underlying causes of so-called idiopathic detrusor overactivity have been disclosed recently by Elbadawi et al. (1993), relating detrusor impairment to detrusor degeneration characterized morphologically by a dysjunction pattern. In this setting, it cannot be overemphasized that better knowledge of the underlying disease will result in more successful treatment of the voiding disability in such patients. Urinary incontinence in elderly patients is not always due to an incompetent urinary sphincter, and urinary retention in this age group is not always the result of a bladder outlet obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2004

Diagnosis and management of patients with overactive bladder syndrome and abnormal detrusor activity.

Overactive bladder syndrome (OABS) is a widely recognized syndrome with symptoms that can include urinary urgency, frequency, nocturia, and incontinence. Although there may be several causative factors for OABS, detrusor overactivity is the most common. In addition, urinary incontinence can also be due to a distinct but equally bothersome condition underactive bladder syndrome, or detrusor underactivity. The incomplete bladder emptying that characterizes detrusor underactivity often arises from impaired contractile function of the detrusor muscle. The variations in etiologies of the two syndromes necessitate patient evaluations tailored to individual symptom presentation. Increased awareness of the differences between the manifestations of OABS and underactive bladder syndrome call for specific approaches to the management of bladder dysfunction.

Humans↗
PubMed1999

Mechanisms underlying the pathogenesis of urinary bladder instability - new perspectives for the treatment of reflex incontinence.

The urine storage ability of the urinary bladder is markedly impaired following inflammation of the urinary bladder and spinal cord injury because of a hyperexcitability of micturition reflexes. Using two rat models of inflammation-induced bladder overactivity and detrusor hyper-reflexia following spinal cord injury we investigated changes in the neuronal pathways to the urinary bladder which may underlie the development of this instability. Our results suggest that among the factors involved in inflammation-induced bladder instability are significant changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide and galanin at the primary afferent level, as well as of the enzyme neuronal nitric oxide synthase (nNOS) at the afferent and postganglionic efferent level. In the lumbar and sacral spinal cord nNOS-immunoreactivity was depleted from dorsal horn neurones in both cystitis and spinal cord injured rats and from preganglionic parasympathetic neurones after spinal cord injury. Distension of the bladder in chronically spinalized rats elicited c-Fos expression in a significantly greater number of neurones throughout the lumbar and sacral segments than in rats with an intact neuraxis. Thus, under pathological conditions rather complicated changes in the synthesis of neuropeptides and nNOS occur at the primary afferent, spinal cord and postganglionic efferent level that together control the activity of the urinary bladder. Further mechanisms like unmasking of silent synapses and axonal sprouting in the spinal cord might further contribute to an increase in activity in micturition reflex pathways. Local cooling of the dorsal spinal cord at the level L6/S1 with temperatures between 14 and 20 degrees C proved a simple technique to control the unstable bladder and restore continence in both inflammation-induced detrusor overactivity and detrusor hyperreflexia following spinal cord injury. The effects of cooling are probably the result of a blockade of synaptic transmission within the dorsal cord which eliminates neuronal overactivity. Thus, local spinal cord cooling could offer a new method to treat bladder instability and reflex incontinence.

Journal Article↗
PubMed1996

Physiological principles for surgical correction of detrusor dysfunction.

Urinary incontinence may be the result of various forms of detrusor overactivity. Several surgical therapies have been devised, but with the exception of procedures to relieve urethral obstruction, none abolishes the overactivity or restores normal micturition. In general, ablative neurosurgery is considered only in patients with chronic neurologic disease. Bladder augmentation is useful in selected patients. The indications for urinary diversion in patients with detrusor overactivity and urge incontinence are quite limited.

Animals↗
PubMed2001

Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic).

Propiverine hydrochloride (propiverine) is a compound that has neurotropic and musculotropic effects on the urinary bladder smooth muscle. Controlled clinical trials have shown its effectiveness in treating detrusor hyperreflexia and in treating patients with symptoms of an overactive bladder: this is true not only for adults but in children and the elderly as well. European and Japanese studies have also documented that propiverine is well tolerated. It is better tolerated than oxybutynin (particularly in regard to frequency and severity of dryness of the mouth). In several Japanese studies authors demonstrated that propiverine is well tolerated on a long-term basis. Voigt reported an adverse event incidence rate of 13% in a follow-up investigation during 10 years of treatment. A post-marketing drug surveillance consisting of 4390 patients provided additional data concerning efficacy and safety of propiverine. It is one of the few drugs recommended for the treatment of detrusor overactivity by the Committee on Pharmacological Treatment during the First International Consultation on Incontinence.

Adult↗
PubMed2002

Influence of central serotonergic mechanisms on lower urinary tract function.

The effects of serotonergic drugs on the central nervous system control of the lower urinary tract have revealed possible approaches for the treatment of detrusor overactivity and urinary incontinence. Studies in animals of the distribution of serotonergic nerves and receptors and the changes in voiding function induced by serotonin (5-hydroxytryptamine [5-HT]) receptor agonists and antagonists, as well as 5-HT reuptake inhibitors, form a basis for the development of such treatments. In rats and cats, spinal reflex circuits involved in voiding function exhibit a dense serotonergic innervation, multiple 5-HT receptors, and sensitivity to various drugs that affect serotonergic transmission. Although there is some evidence in the rat for serotonergic facilitation of voiding, most experiments in rats and cats indicate that activation of the central serotonergic system by 5-HT reuptake inhibitors, as well as by 5-HT1A and 5-HT2 receptor agonists, depresses reflex bladder contractions and increases the bladder volume threshold for inducing micturition. These data indicate that activation of the central serotonergic system can suppress voiding by enhancing efferent control of the urethral outlet and inhibiting the parasympathetic excitatory input to the urinary bladder. The 5-HT receptors and reuptake mechanisms, therefore, represent targets for the development of new treatments of detrusor overactivity and urinary incontinence.

Animals↗
PubMed2006

Placard-shaped in situ vaginal wall sling for the treatment of stress urinary incontinence.

PURPOSE: To evaluate the efficacy of a simple and economic procedure using a placard-shaped in situ anterior vaginal wall sling for the treatment of stress urinary incontinence, with or without cystocele repair. METHODS: From July 2003 to July 2004, 14 female patients (mean age 45.21 years, range 37-57) were operated upon because of stress urinary incontinence (SUI) with the placard-shaped in situ anterior vaginal wall sling technique. The average follow-up period was 11 months (range 4-14.5 months). Twelve patients were operated primarily with this technique and only two patients had undergone previous surgeries for the treatment of SUI (one patient had had two previous surgeries and the other had had one previous surgery). In all patients urethral hypermobility or/and bladder prolapse were observed. Filling cystometry showed sufficient bladder capacity with no detrusor overactivity. RESULTS: No urinary retention was observed in any patient in the postoperative period. While 11 patients have 100% cure of incontinence, three patients started leakage of urine after 1-2 months after the operation (one patient had been operated upon twice before (and who was diabetic and obese) and two patients were primarily repaired by our technique). In two patients, suprapubic tenderness and redness were observed, and were treated by oral antibiotic and anti-inflammatory drugs. CONCLUSION: The placard technique is simple, cost-effective and has low incidence of urinary retention in the post-operative period. The success rate seems to be satisfactory and it can be applicable to patients who are primary cases of SUI with average body mass index. Yet longer term follow up and larger number of patients are needed before final conclusion can be drawn.

Adult↗
PubMed2007

Lower urinary tract symptoms and bladder control in advanced Parkinson's disease: effects of deep brain stimulation in the subthalamic nucleus.

Deep brain stimulation in the subthalamic nucleus (STN) leads to significant improvement in motor function in patients with advanced Parkinson's disease (PD). In this prospective study including 16 patients with PD, we investigated (1) lower urinary tract symptoms (LUTS) by questionnaires International Prostate Symptom Score (IPSS, symptoms only) and Danish Prostate Symptom Score (DanPSS, symptoms and bother of symptoms) and (2) bladder control (assessed by urodynamics) before and after implantation of electrodes in the STN. PD symptoms (Unified Parkinson's Disease Rating Scale score) improved significantly (P < 0.0001), and symptoms of overactive bladder (IPSS) decreased along with the troublesome symptoms of overactive bladder (DanPSS; P < 0.01 for both). Urodynamic parameters before and after implantation of electrodes in the STN, evaluated with and without the stimulation on, did not change significantly.

Adult↗