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PubMed2007

A double-blind, randomized controlled trial of cystometry using saline versus 0.3 M potassium chloride infusion in women with overactive bladder syndrome.

AIM: To evaluate the effect of 0.3 M potassium chloride on cystometric parameters by comparing it with normal saline as a filling solution in women with overactive bladder (OAB). PATIENTS AND METHODS: Twenty-three women with significant OAB symptoms underwent consecutive cystometrograms (CMGs) using 0.9% normal saline (NS) and 0.3 M potassium chloride (KCl), the order of which was randomized for each patient. Individual CMGs were performed by separate investigators and both patients and investigators were blinded to the order in which each solution was given and to the results of the other CMG. RESULTS: Regardless of the nature of the filling solution, the order in which the CMGs were performed had little influence on either first desire to void (FDV, mean 83.5 ml vs. 117.8 ml for first and second CMGs respectively, P = 0.10) or on maximum cystometric capacity (Cmax, mean 265.0 ml vs. 264.4 ml, P = 0.98). KCl produced a significant (24%) reduction in mean Cmax compared to NS (mean 228.6 ml vs. 300.8 ml, P = 0.001), irrespective of the order of infusion. CONCLUSION: This comparative study using 0.3 M KCl versus NS as filling solutions suggests that intravesical potassium may not simply act on urothelial sensory nerve endings; it may also stimulate detrusor muscle contraction. These findings may influence the interpretation of the potassium sensitivity test in patients with OAB symptoms, particularly in those suspected of having interstitial cystitis.

Adult↗

PubMed2006

Nocturnal enuresis and overactive bladder in children: an epidemiological study.

AIMS: To investigate the prevalence and characteristics of nocturnal enuresis (NE) and to examine the prevalence of overactive bladder (OAB) symptoms in primary schoolchildren. METHODS: After conducting an anonymous questionnaire survey about voiding habits and bowel habits in primary schoolchildren, a total of 6917 schoolchildren belonging to 11 primary schools were randomly enrolled in the survey. According to the International Continence Society, we defined NE as any involuntary loss of urine during sleep, occurring more frequently than once per month. Children with NE were subdivided into two groups, monosymptomatic NE (MNE) and enuretic syndrome (ES). To evaluate the characteristic differences of MNE and ES, we assessed the relationships between NE and voiding habits, and episodes of cystitis and constipation. Overactive bladder was defined as increased daytime frequency and/or urge urinary incontinence, and its prevalence was investigated. RESULTS: The response rate to the questionnaire was 76.4%. The prevalence of NE was 5.9% and was inversely related to increasing age. Monosymptomatic NE comprised 59.4% of NE cases. The annual spontaneous resolution rate of MNE was higher than that of ES. Increased daytime frequency, a history of cystitis and infrequent bowel habits were not related to MNE, but were significantly related to ES. The prevalence of OAB was 17.8%. Children with a history of cystitis had a significantly higher rate of OAB than children without it. CONCLUSIONS: Overall, NE and OAB were detected in 5.9% and 17.8% of primary schoolchildren, respectively. The link between NE and OAB symptoms, urinary tract infections and constipation deserves more attention.

Child↗

PubMed2003

Urodynamic verification of an overactive bladder is not a prerequisite for antimuscarinic treatment response.

OBJECTIVE: To investigate the place of urodynamics in the evaluation of patients with symptoms of the overactive bladder by comparing the response to antimuscarinic therapy in those with and with no urodynamically verified symptoms. PATIENTS AND METHODS: In a prospective observational study, 356 female patients with urinary frequency (> or = 8 voids/24 h) and urgency, with or without urge incontinence, underwent cystometry. Patients were diagnosed with detrusor instability if there were spontaneous, uninhibited increases in detrusor pressure during bladder filling. All patients, regardless of urodynamic findings, were subsequently treated with oxybutynin 2.5 mg twice daily and bladder retraining. The outcome was evaluated as the change in urinary frequency and incontinence episodes after 6-8 weeks of treatment. RESULTS: Among 352 evaluable patients, 266 (76%) had detrusor instability on cystometry and the remainder did not. There was no significant between-group difference in mean age, urinary frequency or the number of incontinence episodes at presentation. Both groups improved equally well during oxybutynin and bladder retraining therapy; after 6-8 weeks there was no significant between-group difference for the mean change from baseline in urinary frequency or incontinence episodes. Tolerability profiles were comparable for the two groups. CONCLUSION: Patients with symptoms of an overactive bladder, but apparently normal urodynamic findings, respond equally well to antimuscarinic therapy as those with urodynamically verified symptoms. Such findings cast further doubt on the clinical validity of using invasive urodynamic procedures to characterize patients with irritative lower urinary tract symptoms before starting antimuscarinic therapy.

Adult↗

PubMed2006

Overactive bladder in Parkinson's disease: alteration of brainstem raphe detected by transcranial sonography.

Urinary dysfunction is very common in idiopathic Parkinson's disease (PD) and manifests primarily with symptoms of overactive bladder (OAB). Affection of central serotonergic systems has been suggested to play a role in OAB. The objective of this study was to evaluate whether in PD patients with OAB symptoms a specific alteration of the brainstem raphe (BR), which contains serotonergic neurons, can be detected with transcranial sonography (TCS). Of 116 PD patients enrolled, 19 had PD-related OAB symptoms (OAB+) unlike remaining 97 patients (OAB-). Patients were examined by a sonographer blinded to the clinical data. Reduced echogenicity of BR was found in 12 (63%) OAB+ patients but only in 18 (19%) of 93 assessable OAB- patients (Mann-Whitney U-test, P < 0.001). In OAB+ patients, lower raphe echogenicity score was associated with longer duration of OAB symptoms (anova, P = 0.033). Other TCS findings such as echogenicity of substantia nigra, thalami, lenticular and caudate nuclei, and widths of third and lateral ventricles did not differ between OAB+ and OAB- patients. TCS findings suggest a pathogenetic role of BR in OAB related to PD. Alterations may reflect disturbance of its central serotonergic system.

Adult↗

PubMed2006

Comparison of electric stimulation and oxybutynin chloride in management of overactive bladder with special reference to urinary urgency: a randomized placebo-controlled trial.

OBJECTIVES: To compare the efficacy of electric stimulation (ES), oxybutynin, and placebo in managing the symptom complex of overactive bladder (OAB), particularly urgency. METHODS: A randomized placebo-controlled trial was conducted for 68 patients with OAB, placing emphasis on urinary urgency. The interventions for the 12-week treatment period, conducted by the physiotherapist, who was unaware of the progress and outcome, included a vaginal ES program using biphasic symmetric, pulsed current with a 10-Hz frequency, 400-micros pulse width, 10/5 duty cycle, and varying intensity; and oxybutynin (2.5 mg) or placebo three times per day. Identical preintervention and postintervention assessments included the measurement of warning time, urodynamics, voiding diaries, and King's Health Questionnaire. RESULTS: Of the 68 women who completed this study, 24 were in the ES, 23 in the oxybutynin, and 21 in the placebo group. The between-group comparison showed that significant improvements in daily voided volume, pad count, number of urgency and nocturia episodes, and the domain 2 score and total score of the King's Health Questionnaire existed between the ES and the other groups (all P < or = 0.050). The changes in warning time, maximal voided volume, number of urgency episodes, and frequency were significantly improved between oxybutynin and placebo (all P < 0.013). Additionally, a comparison of the voided volume in uroflowmetry between the ES and placebo groups revealed a greater difference after treatment (P = 0.013). The reduction rate of OAB was 58.4% for the ES, 39.1% for the oxybutynin, and 9.5% for the placebo group (P = 0.036). CONCLUSIONS: ES had the greatest subjective outcome for OAB and was the most effective of the three treatments. Oxybutynin was more effective than placebo.

Adolescent↗

PubMed2003

Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine.

OBJECTIVE: To evaluate the effect of once-daily, extended-release tolterodine on urinary urgency in patients with overactive bladder. METHODS: Patients with urinary frequency (eight or more micturitions per 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral treatment with tolterodine extended release 4 mg once daily (n=398) or placebo (n=374) for 12 weeks. Efficacy was assessed by use of patient perception evaluations. RESULTS: The results presented are a secondary analysis of this double-blind, placebo-controlled study. Of patients treated with tolterodine extended release, 44% reported improved urgency symptoms (compared with 32% for placebo), and 62% reported improved bladder symptoms (placebo, 48%) (both P<.001 compared with placebo). The odds of reducing urgency and improving bladder symptoms were 1.68 and 1.78 times greater, respectively, for patients in the tolterodine extended release group than for patients receiving placebo. In response to urgency, there was a more than six-fold increase in the proportion of patients able to finish a task before voiding in the tolterodine extended release group. The proportion of patients unable to hold urine upon experiencing urgency was also decreased by 58% with tolterodine, compared with 32% with placebo (P<.001). The proportion of patients reporting "much benefit" from treatment was greater for tolterodine extended release than for placebo (43% versus 24%; P<.001). The only adverse events with an incidence of greater than 5% were dry mouth, headache, and constipation, with only dry mouth markedly more frequent with tolterodine than with placebo. CONCLUSION: Tolterodine extended release has demonstrable efficacy in reducing the severity of urinary urgency and is associated with improvements in overactive bladder symptoms that are meaningful to patients.

Administration, Oral↗

PubMed2006

Treatment of the overactive bladder syndrome with muscarinic receptor antagonists: a matter of metabolites?

Antagonists of muscarinic acetylcholine receptors, such as darifenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium, are the mainstay of the treatment of the overactive bladder syndrome. Fesoterodine is a newer drug awaiting regulatory approval. We briefly review the pharmacological activity of their metabolites and discuss how active metabolites may contribute to their efficacy and tolerability in vivo. Except for trospium, and perhaps solifenacin, all of the above drugs form active metabolites, and their presence and activity need to be taken into consideration when elucidating relationships between pharmacokinetics and pharmacodynamics of these drugs. Moreover, the ratios between parent compounds and metabolites may differ depending on genotype of the metabolizing enzymes, concomitant medication, and/or drug formulation. Differential generation of active metabolites of darifenacin or tolterodine are unlikely to influence the overall clinical profile of these drugs in a major way because the active metabolites exhibit a similar pharmacological profile as the parent compound. In contrast, metabolites of oxybutynin and propiverine may behave quantitatively or even qualitatively differently from their parent compounds and this may have an impact on the overall clinical profile of these drugs. We conclude that more comprehensive studies of drug metabolites are required for an improved understanding of their clinical effects.

Benzhydryl Compounds↗

PubMed2004

Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder.

PURPOSE: In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin. MATERIALS AND METHODS: The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition. RESULTS: Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo). CONCLUSIONS: In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.

Adolescent↗

PubMed2002

Effects of adenosine triphosphate dependent potassium channel opener on bladder overactivity in rats with cerebral infarction.

PURPOSE: We evaluated the effect of the adenosine triphosphate dependent K channel opener KRN2391 (N-cyano-N' -(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate) (Kirin Brewery Co., Gunma, Japan) on bladder overactivity induced by middle cerebral artery occlusion. MATERIALS AND METHODS: At 7 days after implantation of a bladder catheter in male Sprague-Dawley rats a cannula for intracerebroventricular administration was implanted and the left middle cerebral artery was occluded with 4-zero monofilament nylon thread. At 22 hours after the induction of cerebral ischemia saline was infused into the bladder at a constant rate (200 microl. per minute) and a cystometrogram was obtained with the rat in the conscious state. KRN2391 (5 microl.) was administered in intracerebroventricular fashion at graded doses (0.15 to 15 microg.). RESULTS: Bladder capacity in conscious rats was significantly reduced after left middle cerebral artery occlusion. Intracerebroventricular administration of KRN2391 significantly increased bladder capacity in cerebral infarcted but not in sham operated rats. CONCLUSIONS: These results show that a adenosine triphosphate dependent K channel opener may be useful for neurogenic bladder overactivity after cerebral infarction via action on the central nervous system.

Animals↗

PubMed2006

Achieving continence with antimuscarinic therapy for overactive bladder: effects of baseline incontinence severity and bladder diary duration.

OBJECTIVE: To examine the continence ('dryness') rate as an outcome measure of the efficacy of antimuscarinic treatment, and to explore how changes in bladder diary duration, baseline severity of urinary incontinence (UI), and study population characteristics affected this outcome. PATIENTS AND METHODS: Urgency UI is a symptom of overactive bladder (OAB) and antimuscarinic agents are a first-line treatment for OAB symptoms; several studies have used dryness rate as an efficacy endpoint, calculated as the percentage of patients who record no UI episodes in a diary period. We performed a post hoc analysis of data from a 12-week, multicentre, randomized, double-blind, placebo-controlled trial of tolterodine extended-release (ER) in patients with symptoms of urinary frequency (> or =8 voids/24 h) and urgency UI (> or =5 episodes/week). Patients with stress UI were excluded. Diary entries from the 3-, 5-, and 7-day periods immediately preceding the baseline and the week 12 visit were used to assess the relationships between the percentage of patients reporting total dryness at week 12, diary duration (3, 5, or 7 days), baseline number of weekly UI episodes (1-6, 7-13, 14-20, > or = 21), and population analysed (intent-to-treat, ITT, or per protocol, PP). The mean changes in weekly UI episodes from baseline to week 12 are also reported by diary duration and baseline frequency of UI for patients treated with tolterodine-ER. RESULTS: The total dryness rates decreased with increasing diary duration and greater frequency of UI at baseline. Analysis of the ITT population also showed lower dryness rates than the PP population. However, the mean reductions in weekly UI episodes for the ITT and PP populations were consistent across diary duration for each level of baseline UI frequency. CONCLUSION: 'Dryness' varies with diary duration, baseline frequency of UI, and the population analysed. Comparisons of dryness rates between studies might lead to erroneous conclusions when these factors are not considered.

Adult↗

PubMed2002

Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).

Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg.

Adult↗

PubMed2006

Effect of the potassium channel opener WAY-133537 on the overactive bladder of spinalized rats.

AIMS: To test the efficacy of WAY-133537 for the treatment of overactive bladder (OAB) in a chronic paraplegic rat model. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were used in this study. Six animals served as normal controls (without spinal cord transaction (ST)), while 42 rats underwent ST at the 10th thoracic vertebra. Two weeks after ST, cystometrogram (CMG) was performed in six randomly chosen animals to ensure the development of neurogenic detrusor overactivity. The remaining 36 rats were divided into three equal groups, 12 received the vehicle as "paraplegic controls," 12 received WAY-133537 0.3 mg/kg, and 12 received WAY-133537 3 mg/kg. Each "paraplegic control" and treatment group was further divided into two sub-groups (n = 6), with CMG at 3 and 4 weeks after ST, respectively. RESULTS: Two weeks after ST, all "vehicle control" rats developed detrusor overactivity with a mean frequency of 0.96 and 1.48 contractions/min and amplitude of 22.96 and 31.22 cm H(2)O with 1- and 2-week treatment, respectively. Neurogenic detrusor overactivity disappeared from 50% of rats that received WAY-133537 0.3 mg/kg for 1 week, and frequency decreased to 0.41 contractions/min. After 2 weeks of treatment, detrusor overactivity vanished from 67% of the animals with even further reduction in the frequency of detrusor overactivity (0.22 contractions/min, P < 0.01). In rats that received 3 mg/kg of the drug for 1 week, detrusor overactivity disappeared from only one animal with a non-significant decline in frequency. Fifty percent of rats given WAY-133537 at the dose of 3 mg/kg/day for 2 weeks manifested no detrusor overactivity. CONCLUSIONS: WAY-133537 shows efficacy in increasing bladder capacity and reducing the frequency of spontaneous bladder contractions after ST in rats without decreasing voiding pressure.

Animals↗

PubMed2002

Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients. DESIGN: A 12-week double-blind, placebo-controlled clinical trial. SETTING: An international study conducted at 167 medical centers. PARTICIPANTS: One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency. INTERVENTION: Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks. MEASUREMENTS: Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older. RESULTS: Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87). CONCLUSIONS: The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age.

Adult↗

PubMed2006

Evaluating the impact of overactive bladder on sexual health in women: what is relevant?

INTRODUCTION: To assess sexual health, relevant, valid, and reliable questionnaires need to be used. AIM: To assess the relevance and content validity of three sexual health questionnaires in women with overactive bladder (OAB) and urinary incontinence. MAIN OUTCOME MEASURES: Sexual Quality of Life Questionnaire--Female (SQoL-F), Sexual Function Questionnaire (SFQ), and Pelvic Organ Prolapse-Incontinence Sexual Function Questionnaire (PISQ). METHODS: Women with OAB and urinary incontinence were recruited from five urology clinics in the United States; those who were interested in participating were mailed questionnaire packets with instructions. Each questionnaire item was followed by three questions regarding the understandability, relevance, and impact of bladder condition when responding to the question. Patients returned the completed questionnaires by mail; clinical information was obtained from chart review. RESULTS: A total of 129 patients (74% response) returned the questionnaires. The mean age was 56 years; 78% were white; 64% were married. In this sample, 64% had urge incontinence; 32% had mixed incontinence; and 4% had stress incontinence. Participants experienced bladder symptoms for a mean of 12.2 years with the following treatments: surgery (43%), bladder training (26%), exercise/biofeedback (42%), and medications (67%). SQoL-F items were understood by more than 97% of the respondents, more than 89% for SFQ, and more than 82% for PISQ. There were two SQoL-F items, one SFQ item, and 11 PISQ items that less than 60% of the respondents deemed relevant to their bladder condition. Correlations among questionnaire items and relevance to bladder condition ranged from 0.04 to 0.64 for the SQoL-F, 0.04 to 0.47 for the SFQ, and 0.01 to 0.58 for the PISQ. CONCLUSION: Women with OAB found the majority of items on all three questionnaires to be relevant to their bladder condition. Of these questionnaires, the SQoL-F had the highest understandability, fewest questions considered irrelevant, and correlated well with OAB symptoms.

Adult↗

PubMed2005

Intravesical injection of botulinum toxin for the treatment of overactive bladder.

PURPOSE OF REVIEW: In recent years, botulinum toxin has been investigated for the treatment of various types of lower urinary tract dysfunctions. This review discusses recently published data related to the therapeutic applications of botulinum toxin in overactive bladder as well as the effects of repeated doses, cross-reactivity between different serotypes, and side effects of the toxin injection into the detrusor muscle. RECENT FINDINGS: Botulinum toxin A has been employed initially in the treatment of neurogenic detrusor overactivity in spinal cord injured patients. Since then, several reports, including a large multicenter study, have confirmed the therapeutic effects of this neurotoxin. The application of botulinum toxin A was extended to the treatment of idiopathic detrusor overactivity and similar results were obtained. Repeated injections of botulinum toxin A had the same sustained benefit. Recently, botulinum toxin B was investigated for the treatments of both neurogenic and idiopathic detrusor overactivity as well as for the management of botulinum toxin A resistant cases. SUMMARY: Although intradetrusal injection of botulinum toxin is not yet an approved treatment for overactive bladder, available data suggest that botulinum toxin can be a therapeutic option in patients with neurogenic and nonneurogenic detrusor overactivity who are refractory to anticholinergic medications. There is a need, however, for further investigation to determine the optimal conditions for these applications. A randomized, double-blinded, placebo-controlled trial to evaluate the therapeutic effects of botulinum toxin is under way.

Administration, Intravesical↗

PubMed2005

Recent advances in basic science for overactive bladder.

PURPOSE OF REVIEW: Detrusor overactivity is a relatively common yet embarrassing symptom complex with significant impact on quality of life. The mainstay of current pharmacological treatment involves the use of muscarinic receptor antagonists, but their therapeutic effectiveness is limited by a combination of limited efficacy and troublesome side effects and has recently been challenged by Herbison et al. Recognition of the limitations of existing therapy has started the search for pharmacotherapeutic agents acting on alternative pathways underlying detrusor overactivity with the intention of improving storage symptoms of urgency, frequency and urge incontinence. RECENT FINDINGS: Recent research has suggested that several transmitters may modulate bladder storage. However, no agents currently available, acting via mechanisms other than muscarinic receptors have entered clinical practice so far. It is clear that far from being a passive container for urine, the urothelium is a crucial area within the bladder wall and its functions are complex and only now beginning to be appreciated. The release of several neurotransmitters from urothelium in response to distension and its action on receptors on sensory neurons is being increasingly recognized. The role for this afferent stimulation on the micturition reflex is gradually gaining importance in the pathophysiology of detrusor overactivity. SUMMARY: In this article, the recent developments in basic science related to the pathogenesis and pharmacological basis for future drug targets for effective management of overactive bladder are discussed.

Adenosine Triphosphate↗

PubMed2003

A review of the overactive bladder in women and men.

Urinary incontinence is a major medical problem that affects people worldwide. More than 17 million people in the United States are affected by the disorder, with billions of dollars in annual costs. The overactive bladder is a major cause of incontinence. The symptoms of frequent urination, pain, and leakage of urine range in severity and debilitation. Overactive bladder produces significant social and physical ramifications that if left untreated result in a dismal quality of life. Newer medications that have been developed allow simple oral treatment. Most patients can now be treated successfully and compassionately.

Activities of Daily Living↗

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↗