Recent Advances in Intravesical Treatment of Overactive Bladder

The traditional medication for overactive bladder (OAB) is antimuscarinic agent, which targets muscarinic receptors. Recent investigations have revealed that muscarinic receptors are present in the urothelium and suburothelial sensory fibers, as well as in the detrusor. Urothelial dysfunction and abnormality of sensory receptor expression or transmitter release in suburothelial nerves could contribute to OAB refractory to antimuscarinics. Intravesical treatment to inhibit abnormal receptor expression or transmitter release in the sensory nerve terminals in the suburothelial space might provide beneficial therapeutic effects in the treatment of OAB. Intravesical resiniferatoxin (RTX) instillation and intravesical botulinum toxin A (BoNT‐A) injection are two promising treatment alternatives for refractory OAB. RTX at a high dose may cause undesired adverse events, such as hematuria, bladder pain or autonomic dysreflexia. RTX at a low concentration can decrease sensory urgency without influencing detrusor contractility; multiple instillations of low‐dose RTX may be required to achieve adequate desensitization of OAB. BoNT‐A, however, has a beneficial effect on detrusor contractility and causes large post‐void residual after injection in some patients. Therefore, careful dosage and injection site adjustment is mandatory to achieve satisfactory results using intravesical therapy.     

Chronic Pelvic Ischemia: Contribution to the Pathogenesis of Lower Urinary Tract Symptoms (LUTS): A New Target for Pharmacological Treatment?

The incidence of lower urinary tract symptoms, including overactive bladder (OAB), is continuing to rise, and is associated with a negative impact on quality of life and a heavy economic burden. A major risk factor for OAB is advancing age. The etiology of OAB is multifactorial and appears to involve myogenic, neurogenic, and urotheliogenic factors. In this article, we review the strengthening preclinical evidence supporting the contribution of chronic pelvic ischemia to the pathogenesis of OAB. In animal models, chronic ischemia induced by arterial injury and a high‐fat diet upregulates markers of oxidative stress and proinflammatory cytokines in the urothelium and lamina propria, and leads to increased expression of nerve growth factor. These processes result in increased afferent activity and an increased frequency of micturition, reflecting a state of bladder hyperactivity. In severe, prolonged cases, bladder overactivity may develop into underactivity. Antimuscarinic therapies are the mainstay of OAB treatment, but their usefulness is limited by modest efficacy and troublesome side‐effects. Our increasing understanding of the contribution of chronic ischemia to OAB is leading toward novel therapeutic options targeting chronic pelvic ischemia and its morphological, functional, and oxidative consequences. Preclinical trials have demonstrated encouraging results with α₁‐adrenoreceptor blockade, phosphodiesterase type 5 inhibition, β₃‐adrenoreceptor agonism, free radical scavenging, and stem cell therapy, in preventing morphological, biochemical and functional changes induced by chronic bladder ischemia.     

Pathophysiology of refractory overactive bladder

Overactive bladder (OAB) is a common condition. The International Continence Society defines OAB as a symptom complex characterized by urgency with or without urge incontinence, usually with frequency and nocturia. The first‐line treatment for OAB includes behavioral therapy, such as caffeine reduction, fluid intake modification, weight reduction, bladder training, and pelvic floor muscle training, as well as treatment with antimuscarinic or β₃‐adrenoceptor agonist medications. However, less than half of all cases achieve satisfactory outcomes following first‐line treatment. Second‐line therapy considered if satisfactory responses are not achieved after 8 to 12 weeks treatment with first‐line therapy include intradetrusor botulinum toxin injection, neuromodulation, and surgical treatment. Patients with refractory OAB may have more severe symptoms or underlying pathophysiologies that were not resolved by the initial medication. The pathophysiologies of refractory OAB include occult neurogenic bladder, undetected bladder outlet obstruction, urethral‐related OAB, urothelial dysfunction with aging, chronic bladder ischemia, chronic bladder inflammation, central sensitization, and autonomic dysfunction. This article discusses the possible pathophysiologies of refractory OAB.     

Promise of Urinary Nerve Growth Factor for Assessment of Overactive Bladder Syndrome

Overactive bladder syndrome (OAB) is highly prevalent bladder disorder in men and women. About 10–15% of the population suffers from urgency frequency with or without urgency urinary incontinence. It is estimated that 50–75% of patients with OAB may have urodynamic detrusor overactivity (DO). Urodynamic study invasive and most of the OAB patients might not accept it as a routine assessment. Therefore, a more objective and non‐invasive test for diagnosis and assessing DO from OAB patients is needed. Recently, urinary nerve growth factor (NGF) has gained great interest in detecting DO in patients with OAB. Urinary NGF level was found to increase in OAB and urodynamic DO. Urinary NGF levels correlated with severity of OAB symptoms. Patients with either idiopathic or neurogenic DO may have increased urinary NGF levels. Urinary NGF levels have been shown to decrease in patients with patients with OAB and DO who have been well treated with antimuscarinics or botulinum toxin injection, but not in those with persistent OAB after treatment. Not all patients with OAB can have an elevated urinary NGF level; it may also be increased in patients with interstitial cystitis/painful bladder syndrome and other lower urinary tract diseases, suggesting urinary NGF expression could be a product of bladder inflammation and a limited specificity of urinary NGF for diagnosing DO. The source of urinary NGF has not yet been fully explored yet. Nevertheless, urinary NGF level is likely to be a promising biomarker for diagnosis of DO from OAB patients, to monitor therapeutic outcome and predict disease progression.     

Neuromodulation for the Treatment of Lower Urinary Tract Symptoms

Neuromodulation therapy incorporates electrical stimulation to target specific nerves that control lower urinary tract symptoms (LUTS). The objectives of this article are to review the mechanism of action, the type of neuromodulation, and the efficacy of neuromodulation mainly according to the results of randomized controlled trials. Neuromodulation includes pelvic floor electrical stimulation (ES) using vaginal, anal and surface electrodes, interferential therapy (IF), magnetic stimulation (MS), percutaneous tibial nerve stimulation, and sacral nerve stimulation (SNS). The former four stimulations are used for external periodic (short‐term) stimulation, and SNS are used for internal, chronic (long‐term) stimulation. All of these therapies have been reported to be effective for overactive bladder or urgency urinary incontinence. Pelvic floor ES, IF, and MS have also been reported to be effective for stress urinary incontinence. The mechanism of neuromodulation for overactive bladder has been reported to be the reflex inhibition of detrusor contraction by the activation of afferent fibers by three actions, i.e., the activation of hypogastric nerve, the direct inhibition of the pelvic nerve within the sacral cord and the supraspinal inhibition of the detrusor reflex. The mechanism of neuromodulation for stress incontinence is contraction of the pelvic floor muscles through an effect on the muscle fibers as well as through the stimulation of pudendal nerves. Overall, cure and improvement rates of these therapies for urinary incontinence are 30–50, and 60–90% respectively. MS has been considered to be a technique for stimulating nervous system noninvasively. SNS is indicated for patients with refractory overactive bladder and urinary retention.     

Urinary Nerve Growth Factor Levels in Urinary Tract Diseases With or Without Frequency Urgency Symptoms

Objectives: To measure urinary nerve growth factor (NGF) levels in patients with several urinary tract diseases under different conditions and compare with NGF levels in patients with overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). Methods: Urinary NGF levels were measured using enzyme‐linked immunosorbent assay (ELISA) and normalized by urinary creatinine concentration. Patients with acute bacterial cystitis, urinary tract stone, urothelial cell carcinoma, and OAB patients after antimuscarinic therapy were evaluated. The urinary NGF levels of OAB, IC/PBS and controls from previous studies were used for comparison. NGF levels were compared among subgroups and between urinary tract diseases with or without associated OAB symptoms. The urinary NGF levels were also compared among natural filling, after normal saline filling and after potassium chloride test in a group of OAB and IC/PBS patients. Results: Patients with acute bacterial cystitis, urinary tract stones or urothelial cell carcinoma had elevated NGF levels that were not associated with the presence of OAB symptoms. Symptomatic cystitis patients who had resolved OAB symptoms after antibiotic treatment had a significant decrease in urinary NGF levels. The urinary NGF levels decreased significantly in OAB patients with effective antimuscarinic treatment for 6 months, but remained stationary and higher than the controls for up to 12 months after treatment. Conclusion: Urinary NGF is not produced solely in patients with OAB or IC/PBS. Acute bacterial cystitis, urinary tract stones and urothelial cell carcinoma can have high urinary NGF production.     

Randomized,Single‐Blind,Parallel Study of the Effectiveness and Safety of Solifenacin versus Propiverine in the Treatment of Overactive Bladder

Objectives: To compare the effectiveness and safety of solifenacin versus propiverine in the treatment of overactive bladder (OAB), in a single‐blind, randomized parallel study. Methods: Sixty‐six patients with OAB (14 men and 52 women) were randomly assigned to groups: solifenacin (5 mg/day) or propiverine (20 mg/day) and treated for 8 weeks. The primary outcome variable was mean change from baseline to end of treatment in urgency of the OAB symptom score (OABSS). Secondary outcomes were bladder diary variables: change over 24 h in the mean number of voids (daytime and nighttime), episodes of micturition urgency and incontinence, and mean volume voided. Patients also completed total OABSS and the King's Health questionnaires. Results: Group backgrounds were comparable except for the male to female proportion; 11:22 for solifenacin (n = 33) versus 3:30 for propiverine (n = 33). Adverse events were 6 of 29 (21%) for solifenacin versus 14 of 26 (54%) for propiverine (P = 0.017). Three patients were withdrawn for voiding difficulty (one in solifenacin and two in propiverine) and one patient for dry mouth (propiverine group). Change in OABSS urgency score was ?2.3 ± 1.4 for solifenacin (n = 28) versus ?1.3 ± 1.7 for propiverine (n = 23), (P = 0.0169). Total OABSS and other individual scores, and voiding diary parameters for both drugs showed improvements; however, between‐group difference was not established. Conclusion: Although both solifenacin 5 mg and propiverine 20 mg were effective in the treatment of OAB, solifenacin appeared to be more effective and tolerable.     

Pharmacologic management of overactive bladder

Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.     

Comparison of Outcome Assessments in Patients with Overactive Bladder Receiving Anticholinergics

Objectives: Patient‐reported outcomes (PRO) reflect treatment benefits from the patient's perspective, and are a subjective method of evaluating the efficacy of overactive bladder (OAB) treatment. We examined the changes in voiding diaries and health‐related quality of life (HRQL) according to patient‐perceived treatment benefits in patients with OAB receiving propiverine. Methods: Thirty‐two patients (mean age ± S.D: 55.1 ± 14.1 years) with OAB were treated with 20 mg propiverine once daily for 12 weeks. The 3‐day voiding diary and the Korean version of the Overactive Bladder Questionnaire (OABq), which includes an eight‐item bothersome symptom scale, as well as 25 HRQL items, were assessed at baseline and at 12 weeks. Finally, patient perception of treatment benefit was evaluated as “no benefit,”“little benefit,” or “much benefit” after treatment. Results: According to patients' perceptions of treatment benefits, 16 (50%) patients perceived “much benefit” from their treatment (group A) and 16 (50%) patients perceived “little benefit” or “no benefit” from their treatment (group B). In both groups, there were significant improvements in the micturation parameters, OABq bothersome symptoms, and total HRQL score after 12 weeks of treatment (P < 0.05). Although there were no significant differences in the voiding diary parameters between the two groups, patients in group A showed significant improvement of the OABq bothersome symptom and total HRQL score compared to group B (P < 0.05). Conclusion: Anticholinergic treatment improves both OAB symptoms and HRQL, and patients' perceptions of treatment benefits correlate better with the OABq than with the voiding diary parameters.     

Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial cystitis (IC)

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic symptom complex that may cause bothersome storage symptoms and pain or discomfort of the bladder, adversely affecting a patient's quality of life. The etiology of IC/BPS remains unclear, and its cause may be multifactorial. Diagnosis of IC/BPS is based on clinical features, and the possibility of other conditions must be ruled out first. Although no definitive treatment is currently available for IC/BPS, various intravesical therapies are used for IC/BPS, including heparin, hyaluronic acid, chondroitin sulfate, pentosan polysulfate, dimethylsulfoxide, liposomes, and botulinum onabotulinumtoxinA (BoNT‐A). This review summarizes the intravesical therapy for IC/BPS and discusses recent advances in the instillation of liposomal‐mediated BoNT‐A and other newly developed intravesical therapies.     

Clinical Impact of Solifenacin on Generic and Symptom‐Specific Quality of Life for Females with Overactive Bladder: Using the Overactive Bladder Symptom Score and Rand Medical Outcomes Study 36‐Item Health Survey

Objectives: We evaluated the effectiveness of antimuscarinic treatment on disease‐specific and generic quality of life (QoL) in females with clinically diagnosed overactive bladder (OAB) by prospectively analyzing improvements in the overactive bladder symptom score (OABSS) and the Rand Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36). Methods: We prospectively recruited newly diagnosed female patients with OAB. Pretreatment disease‐specific symptoms were documented, and generic QoL questionnaires were administered. All subjects received solifenacin 5 mg/day for >8 weeks. Symptoms and general health‐related QoL (HRQoL) were assessed using the OABSS and SF‐36, respectively. Other objective variables, such as maximum urinary flow rate and postvoid residual urine volume, were also evaluated. Results: Seventy‐eight subjects met all inclusion criteria and no exclusion criteria. After 8 weeks, the mean OABSS decreased by approximately 50% compared with baseline (from 9.1 ± 2.8 to 4.5 ± 3.6). All individual scores in OABSS improved after administration of solifenacin. Before treatment, the scores of the study subjects in all SF‐36 domains were significantly worse than the age‐ and gender‐adjusted Japanese national norms (P < 0.01), except the vitality (VT) scale. Intra‐group comparisons between age groups showed worse mental health (MH) scores in all age groups. In the OAB group, three mean SF‐36 scales (physical function [PF], VT, and MH) significantly improved after treatment. Conclusion: Treatment of OAB with solifenacin is associated with significant improvement in generic HRQoL and disease‐specific symptoms at 8 weeks after drug administration. Particularly for generic HRQoL as measured by the SF‐36, solifenacin treatment effectively improves three SF‐36 scores: PF, VT, and MH.     

新型抗胆碱能药物舍尼亭治疗膀胱过度活动症的疗效观察

目的探讨舍尼亭治疗膀胱过度活动症的疗效。方法对60例诊断为膀胱过度活动症的患者行舍尼亭治疗。以自由尿流率的主要参数如最大尿流率(Qmax)、平均尿流率(Qave)、排尿量(VV)和尿道征症状评分(FUSS)、生活质量评分(QOL)为主要疗效指标,来观察治疗效果。结果治疗前尿流率参数值(Qmax、Qave、VV)、FUSS、QOL相比较,≥60岁患者较<60岁患者差异显著(P<0.05);治疗后尿流率参数值(Qmax、Qave、VV)、FUSS、QOL相比较,治疗≥60岁患者疗效较<60岁患者无统计学意义。所有患者治疗前后均有统计学意义(P<0.05),总有效率为85.00%。结论舍尼亭可作为膀胱过度活动症的一种有效治疗手段。     

Prevalence of xerostomia with or without overactive bladder symptoms

Overactive bladder (OAB) occurs idiopathic or secondary to a neurological cause. In addition, OAB may also occur due to xerostomia, because it causes excessive drinking of water. If xerostomia is one of the causes of OAB, treating xerostomia may be effective. This study aimed to investigate the prevalence of xerostomia with or without overactive bladder symptoms. A web-based questionnaire was administered to investigate the prevalence of xerostomia with or without overactive bladder symptoms. The survey included questions concerning age, gender, medical history, medications, OAB symptoms by the Overactive Bladder Symptom Score (OABSS), and xerostomia by the Dry Mouth Scale (DMS). From the analysis, a total of 21 (13.0%) participants were identified as having OAB. The prevalence of xerostomia was six (28.6%) in the OAB group and 14 (10.0%) in the non-OAB group. OABSS and DMS were significantly higher in the OAB group than in the non-OAB group. Urgency score and urgency incontinence score of OABSS were substantially higher in xerostomia participants than non-xerostomia participants. The adjusted odds ratio of OAB showed DMS total score, xerostomia symptoms, accompanying symptoms, and other symptoms that were all significantly associated with OAB. These results suggested that OAB subjects, even untreated subjects, had xerostomia. It may be beneficial for clinicians to perform dry mouth management in parallel with careful choice pharmacotherapy for the wellness of OAB patients.     

Efficacy and Safety of Propiverine and Solifenacin for the Treatment of Female Patients with Overactive Bladder: A Crossover Study

Objectives: To evaluate the clinical efficacy and tolerability of propiverine and solifenacin in female patients with overactive bladder (OAB). Methods: A prospective nonrandomized crossover study of propiverine 20 mg and solifenacin 5 mg was conducted. Female OAB patients were assigned alternately to treatment with propiverine for 8 weeks then solifenacin for 8 weeks (Group P‐S) or solifenacin for 8 weeks then propiverine for 8 weeks (Group S‐P). At baseline, 8th week and 16th week, symptoms were assessed using overactive bladder symptom score (OABSS). Results: A total of 121 patients were enrolled. Overall, 38 patients (31.4%) discontinued or dropped out and 83 patients were available for analysis (39 in Group P‐S and 44 in Group S‐P). In both groups, the total score and each score of OABSS were significantly improved after 8 weeks compared with baseline. In only Group P‐S (changing over from propiverine to solifenacin), urgency score in the 16th week was further improved significantly compared with the 8th week. The most bothersome symptom at baseline was urgency incontinence (50.6%), followed by urgency (37.3%). Even after symptom improvement, more than half of the patients were bothered by urgency or urgency incontinence. The incidence of adverse events of moderate and severe grade was higher during propiverine treatment than solifenacin (11.1% vs 2.9%, P = 0.039). Conclusion: Propiverine 20 mg and solifenacin 5 mg were effective for treating female OAB patients. Urgency was further improved after switching from propiverine to solifenacin, but not after switching from solifenacin to propiverine. Solifenacin was better tolerated than propiverine.     

Depression,Anxiety and the Bladder

Depression and anxiety are common mental illnesses. It is recognized that depression/anxiety causes physical changes, including insomnia, anorexia, and bladder dysfunction. We aimed to delineate bladder dysfunction in patients with depression/anxiety by reviewing the literature. We performed a systematic review of the literature to identify the frequency, lower urinary tract symptoms (LUTS), urodynamic findings, putative underlying pathology, and management of bladder dysfunction in patients with depression/anxiety. From a recent survey of a depression cohort (at a psychiatry clinic), the frequency of bladder dysfunction in depression is lower (up to 25.9%) than that in Parkinson's disease (up to 75%) and stroke (up to 55%), whereas it is significantly higher than that in age‐matched controls (around 10%). In both the depression cohort and the psychogenic bladder dysfunction cohort (at a urology clinic), the most common LUTS was overactive bladder (OAB), followed by difficult urination and infrequent voiding. Compared with severe LUTS, urodynamic findings were dissociated; i.e. urodynamic findings were normal except for increased bladder sensation without detrusor overactivity for OAB (50% of all patients), followed by underactive detrusor without post‐void residual for difficult urination. The effectiveness of serotonergic or anti‐cholinergic medication for ameliorating OAB in the patients awaits further study. In conclusion, although the frequency of LUTS among the depression cohort is not elevated, depression/anxiety is obviously a risk factor for OAB. This finding presumably reflects that the bladder is under emotional control. Amelioration of bladder dysfunction is an important target in treating patients with depression/anxiety.     

Overactive bladder with urodynamic study-induced bladder pain: An overactive bladder subtype with symptoms similar to those of interstitial cystitis/painful bladder syndrome

Overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS) are 2 lower urinary tract disorders with urgency and bladder pain for diagnosis and with several other shared symptoms. Because of their overlapping symptoms, precise differential diagnosis of OAB and IC/PBS remains difficult. Thus, we characterize a subgroup of OAB with bladder pain (OAB-BP) that can be differentiated from OAB alone by urodynamic study (UDS) findings. We also further examined the clinical presentations and urodynamic parameters of OAB alone, OAB-BP, and IC/PBS. Data were collected between September 2018 and April 2019. Patients were categorized into 3 groups, OAB-alone (no bladder pain during UDS, n = 39), OAB-BP (with bladder pain during UDS, n = 35), and IC/PBS (the comparator, n = 39). Chi-square tests were used to compare OAB alone, OAB-BP, and IC/PBS with respect to their clinical presentations and urodynamic parameters. Factors with P < .05 were further analyzed through post hoc comparisons with Bonferroni adjustment. An unique subgroup of OAB patients was identified (i.e., OAB-BP), bladder pain can only be induced at maximal cytometric capacity during UDS. We also identified that the case histories and UDS parameters (e.g., low first desire, normal desire, and maximum cytometric capacity) of the OAB-BP group were more similar to those of the IC/PBS group than to those of the OAB-alone group. The OAB-BP group and the IC/PBS group reported more intrusive, longer-lasting symptoms before their final diagnoses, more extensive family history of urinary tract disorder, and more associated comorbidities (e.g., irritable bowel syndrome, and myofascial pain) than the OAB-alone group. The UDS assessment induced bladder pain in the OAB-BP group to reveal their hidden symptoms. Careful attention to patient history and sophisticated UDS evaluation may help to identify this unique OAB group.     

Effect of Imidafenacin before Sleeping on Nocturia

Objectives: Clinical efficacy, influence on quality of life (QOL), and safety of imidafenacin before sleeping were assessed in patients with overactive bladder (OAB) who suffered from nocturia. Methods: A total of 60 OAB patients with a mean age of 74 years (45 men and 15 women) who mainly complained of nocturia were enrolled. Imidafenacin (0.1 mg) was administered once daily before sleeping for four weeks. Then the patients were divided into two groups, “a stable‐dose group” with sufficient efficacy who remained on 0.1 mg of imidafenacin daily, and “a dose‐escalation group” with insufficient efficacy in whom the daily dose of imidafenacin was increased to 0.2 mg before sleeping. Lower urinary tract symptoms and postvoid residual volume (PVR) were examined before treatment and after 4 and 8 weeks of imidafenacin therapy. Results: In the stable‐dose group, nighttime frequency decreased significantly from 3.4 ± 1.1 to 2.3 ± 1.1 and 2.6 ± 2.0 times after four and eight weeks, respectively. In the dose‐escalation group, nighttime frequency did not change significantly (from 3.8 ± 1.5 to 3.6 ± 1.8 times) at four weeks, but decreased significantly to 2.8 ± 1.4 times at eight weeks. Daytime frequency, OAB symptom score, and IPSS‐QOL index score were significantly improved in both groups at four and/or eight weeks. There was no increase of PVR and no serious adverse events. Conclusion: Administration of imidafenacin at 0.1–0.2 mg once daily before sleeping was safe and effective for the treatment of OAB with the main symptom of nocturia.     

Overactive Bladder in Female Patients with Chronic Diseases Visiting Primary Care Doctors: Effect of Age on Prevalence and Bothersomeness

Objectives: We evaluated the effects of age on the prevalence and bothersomeness of overactive bladder (OAB) in female patients with chronic diseases visiting primary care doctors. Methods: We used the pooled data of the SURPRISE survey in which 121 doctors and 1388 female patients aged 40 years or older responded to questionnaires. Results: The OAB prevalence rate in patients was estimated by doctors to be 9.5%. However, the OAB prevalence rate according to patients, as defined by the OAB symptom score, was 22.3%. The rate was increased with age. The number of patients with OAB was much higher than estimated by doctors. Approximately 25% of patients were dissatisfied with their present urinary condition. The rate was increased with age. Dissatisfaction with present urinary condition was strongly correlated with severe urgency score in all age groups. In elderly patients, contribution of urgency incontinence and nocturia to dissatisfaction was also increased. Thirteen percent of patients were receiving treatment for their OAB. However, 15.8% were untreated, regardless of having OAB, suggesting that treated patients comprise less than half of all OAB patients. This tendency was observed in all age groups. In the correlation between satisfaction with pharmacological treatment and each OAB symptom, contribution of urgency to satisfaction with pharmacological treatment was the highest. Conclusion: Urgency is the most bothersome symptom and shows the highest contribution to treatment satisfaction. In elderly patients, urgency incontinence and nocturia are proportionally greater problems. Management of urgency is essential for improving quality of life and satisfaction with treatment in OAB patients.     

Efficacy,Safety and Tolerability of Fesoterodine in Asian Patients with Overactive Bladder

Objectives: To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg once daily (QD) compared with placebo in Asian subjects with overactive bladder (OAB) after 12 weeks of treatment. Methods: This phase II, dose‐finding study consisted of a 2‐week placebo run‐in period followed by a 12‐week, randomized, double‐blind, placebo‐controlled, treatment period. Eligible subjects were aged ≥20 years with ≥8 micturitions per 24 h and ≥1 urgency urinary incontinence (UUI) episodes per 24 h reported in a 3‐day diary. The subjects were randomized to receive placebo, fesoterodine 4 mg, or fesoterodine 8 mg QD for 12 weeks. Results: Of 1232 subjects who entered the placebo run‐in period, 951 received double‐blind treatment. The mean number of UUI episodes per 24 h at baseline was 2.2 among the three treatment groups. The two fesoterodine groups showed statistically significant decreases from baseline in the mean number of UUI episodes per 24 h at week 12 (primary endpoint) compared with placebo. Most all‐causality adverse events (e.g. dry mouth and constipation) were mild or moderate. The percentage of subjects with severe adverse events was low and similar among the treatment groups (placebo, 1.3%; fesoterodine 4 mg, 1.9%; fesoterodine 8 mg, 1.0%). Conclusion: Fesoterodine 4 and 8 mg QD were significantly better than placebo in improving OAB symptoms. Overall, the two fesoterodine dosing regimens were well tolerated. These results suggest that fesoterodine 4 and 8 mg QD are effective and well‐tolerated treatments for OAB in Asian subjects.