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PubMed2004

Vesical pacing: pacing parameters required for normalization of vesical electric activity in patients with overactive bladder.

There are several modalities for the treatment of the overactive bladder (OAB), but the results may not be satisfactory. A recent study has demonstrated that the OAB has a dysrhythmic electric activity that seems to result from a disordered vesical pacemaker. We hypothesized that vesical pacing may correct the irregularities of the vesical electric waves and consequently normalize the vesical contractility. In this communication, we primarily defined the adequate pacing parameters required for correction of the vesical dysrhythmia. 36 patients with OAB were divided into a study group (22; 13 women; mean age 40.2 years) and a control group (14; 8 women; mean age 41.8 years). Ten healthy volunteers (6 women; mean age 39.8 years) were included in the study. Three 28-gauge cardiac pacing electrodes were hooked to the vesical mucosa: one (pacing) to the vault, and two (recording) to the lateral wall. Electric activity at rest and during stimulation of the pacing electrode was recorded in the study group and the healthy volunteers. In the control group, recording was done without pacing. Reproducible regular triphasic SWs were recorded from the 2 electrodes of the healthy volunteers with a similar pattern from the 2 electrodes of each individual subject. The optimal pacing parameters we determined were: an amplitude of 5 mA, a pulse width of 200 ms and a frequency of 20% higher than the frequency of the basal vesical waves. Vesical pacing effected a significant increase of waves' variables. The OAB patients exhibited a "dysrhythmic" wave pattern which was normalized during vesical pacing using the aforementioned pacing parameters. The optimal parameters required for vesical pacing of the dysrhythmic waves of the OAB were determined and succeeded in normalization of the vesical electric activity. Vesical pacing is suggested to be used as a therapeutic tool for the treatment of the OAB.

Adult↗

PubMed2006

The promise of beta3-adrenoceptor agonists to treat the overactive bladder.

The detrusor muscle contains beta-adrenoceptors (beta-ARs), of which two subtypes--beta1-AR and beta2-AR--have been identified in most species. Although beta2-AR has an important role in muscle relaxation, evidence suggests that a third subtype--beta3-AR--mediates relaxation of human detrusor muscle. This article reviews the evidence for beta3-AR in human detrusor muscle and urothelium and discusses the potential use of beta3-AR agonists for the treatment of overactive bladder. In addition, the cAMP-dependent and -independent mechanisms of relaxation by way of beta-ARs in rat detrusor muscle, with and without pre-contraction, are reported. Finally, the consequences of mutation of a beta3-AR gene (relating to the pathophysiology of idiopathic detrusor instability) are discussed.

Adrenergic beta-3 Receptor Agonists↗

PubMed1999

Tolterodine in the treatment of overactive bladder: analysis of the pooled phase II efficacy and safety data.

OBJECTIVES: To summarize the efficacy and safety of tolterodine from the pooled data of four multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group Phase II studies in patients with urodynamically proved overactive bladder (detrusor instability or detrusor hyperreflexia) and to analyze the concentration-effect relation. METHODS: After a 1-week run-in period to establish baseline values, 319 patients were randomized to receive placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily. Micturition diary and urodynamic variables and subjective urinary symptoms were assessed after 2 weeks of treatment. Patients were classified as "extensive" or "poor" metabolizers of tolterodine on the basis of serum levels of tolterodine. RESULTS: A per-protocol analysis of efficacy in 262 patients showed dose-related improvements in micturition diary and urodynamic variables. A dosage of 4 mg twice daily was, however, associated with an increase in residual urinary volume. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable between placebo and tolterodine dosages of 2 mg twice daily. No serious drug-related adverse events were observed, and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. Changes in urodynamic variables were found to be related to the sum of unbound serum concentrations of tolterodine and its major active 5-hydroxymethyl metabolite. In poor and extensive metabolizers of tolterodine, exposure to the sum of these active moieties was similar, and the efficacy and safety profiles were comparable. CONCLUSIONS: The results of this pooled data analysis indicate that tolterodine offers an effective treatment for patients with urinary symptoms attributable to overactive bladder. The optimal dosage is 1 to 2 mg twice daily, irrespective of metabolic phenotype.

Adolescent↗

PubMed1998

Testosterone-induced prostatic growth in the rat causes bladder overactivity unrelated to detrusor hypertrophy.

BACKGROUND: Testosterone treatment of rats produces prostatic hypertrophy and detrusor overactivity. Whether or not the detrusor overactivity can be related to an increase in the responsiveness of lower urinary tract smooth muscles is not known. METHODS: Male Sprague-Dawley rats were given daily injections of testosterone propionate for 2 weeks. Effects on cystometric parameters and on the responsiveness of isolated detrusor, urethral, and prostate smooth muscle preparations to drugs and electrical field stimulation were investigated. RESULTS: Testosterone treatment increased prostatic weight twofold (controls, 768 mg; testosterone-treated, 1,478 mg), but not bladder weight (103 mg vs. 116 mg). Micturition pressure (77%), bladder capacity (75%), residual volume (56%), and micturition volume (83%) increased significantly in treated animals, and bladder overactivity developed. No effect of intraarterial doxazosin on these changes was observed. The differences in urodynamic parameters between control and testosterone-treated rats could not be correlated with changes in bladder, urethral, or prostate excitatory innervation, as revealed by responses to electrical field stimulation, or by smooth muscle responses to different contractant drugs. CONCLUSIONS: Some of the urodynamic effects seen after testosterone treatment seem to be caused by the mechanical obstruction of the enlarged prostate. Since there were no changes in smooth muscle responsiveness, it is suggested that the bladder overactivity observed can partly be related to testosterone-induced changes of the micturition reflex at the lower urinary tract, spinal, and/or supraspinal levels.

Animals↗

PubMed2006

Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence.

PURPOSE: Urge urinary incontinence is the involuntary leakage of urine commonly occurring in older adults, particularly women. Preclinical evidence suggests that urge urinary incontinence may occur due to up-regulation of tachykinin mediated bladder/spinal reflex signaling. This study tested the hypothesis that aprepitant, a neurokinin-1 receptor antagonist, may be efficacious in the treatment of urge urinary incontinence. MATERIALS AND METHODS: This was a double-blind, randomized, placebo controlled, parallel group pilot study in which postmenopausal women with a history of urge urinary incontinence or mixed incontinence (with predominantly urge urinary incontinence) were assigned to receive a 160 mg capsule of aprepitant (61) or placebo (64) once daily for 8 weeks. The primary end point was percent change from baseline in average daily micturitions assessed by a voiding diary. Secondary end points included average daily total urinary incontinence and urge urinary incontinence episodes, and urgency episodes. RESULTS: Aprepitant significantly decreased the average daily number of micturitions compared with placebo at 8 weeks. The between-group treatment difference expressed as percent change from baseline was -6.8%, 95% CI (-12.5, -1.1) (p = 0.019). The average daily number of urgency episodes was also significantly reduced compared to placebo (p = 0.049). The average daily number of urge urinary incontinence and total urinary incontinence episodes were also reduced, although the difference was not statistically significant. Aprepitant was generally well tolerated and adverse experiences were generally mild. CONCLUSIONS: Results of this initial study suggest that neurokinin-1 receptor antagonism may represent a novel therapeutic approach to treating overactive bladder syndrome.

Adult↗

PubMed2000

The overactive bladder in childhood: long-term results with conservative management.

PURPOSE: Idiopathic detrusor overactivity has not been thoroughly investigated and its natural history remains largely anecdotal. Bladder overactivity resulting from a neurogenic, anatomical or medical condition has been well described. Therefore, we assessed the long-term results of conservative treatment of children with idiopathic symptomatic refractory detrusor instability. MATERIALS AND METHODS: We reviewed the records of 58 patients who had an isolated finding of uninhibited contractions on urodynamics performed for refractory enuresis and daytime wetting between 1988 and 1994. Study exclusion criteria were chronic urinary tract infection, neurological lesion, anatomical abnormality of the lower urinary tract and less than 12 months of followup. RESULTS: Of the 30 children who met our study inclusion criteria 26 (87%) had complete (21) or significant (5) symptom resolution. Average time to resolution was 2.7 years (range 0.2 to 6.6). Patients with a 50% to 90% bladder capacity expected for age were more likely to benefit from therapy than those with a bladder capacity outside of this range. Age and gender were not significant predictors of resolution although girls were more likely to have resolution than boys. CONCLUSIONS: Idiopathic detrusor instability is amenable to conservative management in the majority of patients during a prolonged period. We advocate thorough urological and urodynamic evaluation to identify idiopathic detrusor instability as an etiology of enuresis and daytime wetting in complicated cases.

Adolescent↗

PubMed2005

Acupuncture for overactive bladder: a randomized controlled trial.

OBJECTIVE: To compare acupuncture treatment for overactive bladder with urge incontinence with a placebo acupuncture treatment. METHODS: Eighty-five women enrolled in this randomized, placebo-controlled trial. Women were randomly assigned to either receive an acupuncture treatment expected to improve their bladder symptoms, or a placebo acupuncture treatment designed to promote relaxation. They underwent cystometric testing, completed a 3-day voiding diary, and completed the urinary distress inventory and incontinence impact questionnaire, validated quality-of-life inventories, before and after 4 weekly acupuncture treatments. The primary endpoint was number of incontinent episodes over 3 days. Secondary endpoints included voiding frequency and urgency, cystometric bladder capacity, maximum voided volume, and the urinary distress inventory and incontinence impact questionnaire symptom scores. RESULTS: Seventy-four women completed all aspects of the study. Women in both treatment and placebo groups had significant decreases in number of incontinent episodes (59% for treatment, 40% for placebo) without a significant difference in the change between the groups. Women in the treatment group had a 14% reduction in urinary frequency (P = .013), a 30% reduction in the proportion of voids associated with urgency (P = .016), and a 13% increase in both maximum voided volume and maximum cystometric capacity (P = .01). Both groups also had an improvement in the urinary distress inventory and incontinence impact questionnaire scores (54% decrease for treatment, 30% decrease for placebo, P < .001 for the difference in change between the groups). CONCLUSION: Women who received 4 weekly bladder-specific acupuncture treatments had significant improvements in bladder capacity, urgency, frequency, and quality-of-life scores as compared with women who received placebo acupuncture treatments. LEVEL OF EVIDENCE: I.

Acupuncture Therapy↗

PubMed2005

Overactive bladder: achieving a differential diagnosis from other lower urinary tract conditions.

Overactive bladder (OAB) is a debilitating condition characterised by an urgent need to urinate (urgency), often with urinary frequency and, in some cases, urgency incontinence and nocturnal frequency. Patients often adopt complex adaptive behaviours to cope with their symptoms as OAB can compromise all dimensions of a patient's quality of life. Most OAB patients present initially to their primary care physician. Diagnosis is based on presenting symptomatology and does not require any invasive tests. Direct questioning about symptoms is important in achieving a differential diagnosis. The most common condition to be considered when working towards a differential diagnosis is a urinary tract infection (UTI). However, some physicians have expressed concerns about identifying the small number of cases where bladder cancer is a potential underlying aetiology for the symptoms of OAB. In this review, we examine the prevalence and patient profiles for these bladder conditions and their presenting symptomatology. We also review tests that may be recommended to exclude a diagnosis of UTI or bladder cancer and present a diagnostic algorithm suitable for office-based primary care practice.

Algorithms↗

PubMed2003

Treatment of the overactive bladder: where we stand in 2003.

The understanding and management of overactive bladder (OAB) continue to evolve. However, argument persists as to the exact incidence of the disease and the underlying pathophysiology of the symptom complex. Individual differences in symptomatic impact and, more importantly, personal coping partially account for the disparity noted among demographic estimates currently extant. Likewise, the underlying pathophysiology that leads to overt OAB syndrome is, as yet, incompletely characterized. Muscarinic receptor behavior provides partial explanation, but other complex underlying receptor and neurotransmitter interactions probably are also a component of the presentation. Current state-of-the-art therapy relies on an exclusionary diagnosis prior to the inception of therapy. Ideally, optimal therapy involves behavioral and pharmacologic interventions combined to maximize therapeutic results. Antimuscarinic therapy provides only a degree of relief from the bothersome symptoms of OAB. As yet, few options exist for patients who have previously failed oral antimuscarinic intervention. Herein, the evolving OAB landscape will be considered as it currently stands in 2003. The current lack of optimal symptom control will most assuredly lead to the development of new pathways for OAB treatment.

Journal Article↗

PubMed2003

Overactive bladder in special patient populations.

It is now well accepted that overactive bladder (OAB) negatively affects the quality of life of a large number of persons and that the primary mode of therapy is the use of medication-currently antimuscarinic agents. However, it is also important for physicians to understand how the use of these drugs affects specific groups of patients. Most of the concern in this area focuses on the potential for these populations to experience certain adverse events or side effects from the use of antimuscarinic agents; this has prevented these drugs from being prescribed in these populations to the same degree as in the general population of OAB sufferers. The purpose of this article is to review these specific populations of OAB patients, including pediatric, geriatric, and pregnant patients, men with prostate problems, and patients in whom OAB is of neurogenic origin, and to discuss what is currently known about the use of antimuscarinic agents in these groups.

Journal Article↗

PubMed2006

Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers as a possible medical treatment of the overactive bladder and urge incontinence.

Urinary incontinence affects millions of people worldwide and also represents a social problem. People of all ages suffer from urinary incontinence. The disease is found in about 30% of women aged 30 to 60 years. There are different types of incontinence. Urge incontinence is the most often pharmacologically treated type. The mainly used substances belong to the class of antimuscarinic drugs. Their use is limited by several side effects. Furthermore, in some patients anticholinergic medication is ineffective and antimuscarinics used as single medication do not lead to a sufficient therapeutic effect. Other possible pharmacological substances for treatment of overactive bladder (detrusor instability) associated with urge and urge incontinence are the selective beta-adrenoceptor-agonists which are mainly responsible for the adrenergic mediated relaxation. It depends on the species, which beta-adrenoceptor-subtype (the beta2- and/or beta3-adrenoceptor) mainly mediates the relaxation. Non selective beta-adrenoceptor-agonists exhibit serious cardiovascular side effects like tachycardia or decrease of blood pressure by stimulating beta1- and beta2-adrenoceptors. These side effects should be decreased when using selective agonists. Additionally, substances whose targets are membrane channels of muscle cells could be interesting for treatment of overactive bladder. This group includes L-type calcium antagonists and potassium channel openers of ATP-sensitive potassium channels or BK channels. Especially the local use of the pharmacologically very potent calcium antagonists could be an interesting therapeutic approach, since systemic cardiovascular side effects were avoided. After chronic oral treatment with different calcium antagonists effects on the detrusor muscle were reduced or could not be detected, possibly due to an upregulation of 1,4-dihydropyridine-sensitive potassium channels. A very interesting approach is the use of potassium channel openers said to be selective for the urinary bladder. If there is a selectivity for the detrusor muscle, cardiovascular side effects were reduced. Possibly, the local use is a useful application form. Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers are pharmacological approaches, which are not yet available for clinical use.

Adrenergic beta-Agonists↗

PubMed2003

Effects of methoctramine on bladder overactivity in a rat model.

OBJECTIVES: To determine the functional effects of methoctramine as an M(2) muscarinic receptor antagonist on isolated detrusor strips in vitro and bladder overactivity in vivo in rats. METHODS: A total of 114 Sprague-Dawley rats were used in the present study. Isolated rat detrusor strips were contracted by depolarizing the preparations with carbachol. Methoctramine was added to the tissue bath in increasing concentrations, and contraction inhibition was assessed. Isovolumetric contractions were evoked by electrical stimulation using a bipolar electrode. Efficacy against bladder instability was evaluated using the obstructed hypertrophied bladder model in the rat. The acetic acid bladder cystometry model was used to assess the efficacy of methoctramine in neurogenic detrusor overactivity. RESULTS: Methoctramine inhibited carbachol-induced bladder contractions significantly in isolated rat detrusor strips in a concentration-dependent manner. The amplitude of electrically evoked isovolumetric contractions was decreased significantly after methoctramine exposure. In vivo methoctramine administered intravenously significantly increased the voiding interval and bladder compliance. In addition, a decrease occurred in the number of spontaneous contractions during the filling phase in a model of neurogenic and obstruction-induced detrusor overactivity. CONCLUSIONS: M(2) antagonists in general may represent a new useful class of drug worth considering in the treatment of bladder overactivity.

Animals↗

PubMed2005

["Pathophysiology and treatment of the overactive bladder"].

The International Continence Society (ICS) recently derived a consensus symptomatic definition of overactive bladder (OAB) as urinary urgency, with or without urge incontinence, usually with frequency and nocturia. These symptom combinations are suggestive of urodynamically demonstrable detrusor overactivity. The etiology of OAB falls into two broad categories: neurogenic and nonneurogenic. It is not easy to confirm the etiology of OAB in patients with bladder outlet obstruction and neurological disease. This debate has attempted to examine the pathophysiology of OAB and to determine the optimal treatment strategy in a patient with two diseases possibly causing OAB. A 75-year-old man visited our hospital due to symptoms of OAB (urgency, nocturia, and urge incontinence) occurring after cerebrovascular accidents. Urge incontinence worsened concomitantly with the appearance of turbid urine. Urinary tract infection was accompanied by 84 ml of post-void residual. The prostate volume and PSA value were 28 ml and 1.2 ng/ml, respectively. The total International Prostate Symptom Score (IPSS) and Quality of Life (QOL) Index were 23 and 5, respectively. IPSS for storage symptoms was higher than that for obstructive symptoms. The maximum flow rate, measured after treatment for UTI, was 9.4 ml/s. Two debaters discuss the treament modality, TURP, or pharmacotherapy.

Aged↗

PubMed2004

Trospium chloride in the management of overactive bladder.

Trospium chloride is an orally active, quaternary ammonium compound with antimuscarinic activity. It binds specifically and with high affinity to muscarinic receptors M(1), M(2) and M(3), but not nicotinic, cholinergic receptors. It is hydrophilic and does not cross the normal blood-brain barrier in significant amounts and, therefore, has minimal central anticholinergic activity. Peak plasma trospium chloride concentrations are attained approximately 5-6 hours after oral administration, which should occur before meals as concurrent food ingestion significantly reduces trospium bioavailability. Trospium chloride undergoes negligible metabolism by the hepatic cytochrome P450 system; few metabolic drug interactions are known. While trospium chloride dosage adjustments based on age or sex appear unwarranted, such adjustments may be needed in patients with severe renal impairment. Direct comparative studies in patients with overactive bladder indicate that trospium chloride is at least as effective as oxybutynin and tolterodine. Placebo-controlled studies have also confirmed the efficacy of trospium chloride in terms of improved urodynamic parameters; small-scale, noncomparative studies have documented significant trospium chloride-induced improvements in patients with reflex neurogenic bladder, postoperative bladder irritation and radiation-induced cystitis; and observational studies including >10,000 patients have also revealed favourable findings for trospium chloride, including a marked decrease in incontinence episodes and substantial improvement in health-related quality of life. Trospium chloride is generally well tolerated, and significantly more so than immediate-release oxybutynin. The most frequent adverse events, occurring in >1% of trospium chloride-treated patients, are dry mouth, dyspepsia, constipation, abdominal pain and nausea. Available for many years in several countries outside North America, trospium chloride is likely to develop an important role in the management of overactive bladder following its approval in the US on 28 May 2004.

Benzhydryl Compounds↗

PubMed2002

Incidence and prevalence of overactive bladder.

Recent changes in terminology, diagnosis, and therapy have refocused attention on overactive bladder (OAB). This symptom syndrome is highly prevalent worldwide and significantly impairs the quality of life of those who suffer from it. Accurate epidemiologic incidence and prevalence studies of OAB have been hampered in the past by, among other issues, a generalized lack of agreement regarding definition of the disorder, and consequently, accurate case finding. This obstacle resulted in considerably wide estimates in the reported incidence and prevalence of OAB in the literature. A new symptom-based definition of OAB, formally adopted by the Standardization Committee at a recent International Continence Society meeting, should provide a framework for future epidemiologic studies. Current estimates of incidence, prevalence, effects on quality of life, and societal costs may need to be reassessed based on these new data.

Humans↗

PubMed2006

Disruptive effects of overactive bladder and urge urinary incontinence in younger women.

Although most studies of overactive bladder (OAB) have investigated older patients, many younger women suffer from OAB syndrome with and without urge urinary incontinence. OAB in these women is associated with an increased risk of depression, sexual dysfunction, sleep disruption, and lost productivity in the workplace. Many patients adopt coping strategies rather than seeking treatment; therefore, available treatments are underused in this population.

Adult↗

PubMed2006

Management of overactive bladder and urge urinary incontinence in the elderly patient.

The symptoms of overactive bladder (OAB) and urge urinary incontinence may occur at any age but are particularly common among the elderly. These symptoms are associated with significant morbidity and often have a profound impact on patient quality of life. Urinary incontinence is an important contributor to the complications and economic cost of OAB for both community-dwelling and institutionalized elderly individuals. Many patients with OAB do not seek treatment because of embarrassment, fear of surgery, or the misperceptions that the problem is untreatable or is a normal and inevitable consequence of aging. Nonpharmacologic therapies improve bladder control by modifying lifestyle and behavior to prevent urine loss. This requires patient and caregiver motivation and can be time consuming. Improved results may be obtained by combining these strategies with pharmacotherapy or by means of pharmacotherapy alone. The most commonly used pharmacologic agents are the muscarinic receptor antagonists. These include oxybutynin, tolterodine, and three agents that have recently been approved for use in the United States: trospium, darifenacin, and solifenacin. In general, these therapies are well tolerated and safe; however, the selection of an optimal agent merits careful consideration. For elderly patients, important considerations include tolerability, absence of drug interactions, and the availability of a range of dosages to tailor treatment to individual patients. Primary care practitioners and geriatricians can have a key role in successful diagnosis and treatment of OAB. It is important for these physicians to realize that satisfactory outcomes may be achieved within the scope of a busy outpatient practice.

Aged↗

PubMed2002

Definition and epidemiology of overactive bladder.

The Standardisation Subcommittee of the International Continence Society (ICS) now recognizes overactive bladder (OAB) as a "symptom syndrome suggestive of lower urinary tract dysfunction." It is specifically defined as "urgency, with or without urge incontinence, usually with frequency and nocturia." The ICS definition was not formulated until January 2001 and was not formally approved until September 2001. Therefore, collection and discussion of the epidemiologic characteristics of OAB are somewhat hampered by the different definitions of this condition used by different investigators. Most communications that appeared before 2000 more often described characteristics of incontinence rather than OAB, and the estimates of OAB prevalence within those studies varied significantly. Until recently, little definite epidemiologic information was available on the prevalence and comorbidities of OAB. An important challenge in treating OAB is to increase awareness of this significant problem worldwide and to impress on other specialists and primary care physicians the importance of identifying this clinical problem and managing it in a way that will maximize quality-of-life improvement while minimizing morbidity.

Female↗