mm) at their department, which they say causes only minimal discomfort and can be used withonly intraurethral lidocaine gel.The article by Reitz et al chronicles experience in 200 patients with neurogenic overactivity,

188 of whom were already receiving CIC, 12 being indwelling catheter drainage. A total of 167patients had spinal cord injury as the etiology of the dysfunction, 22 myelomeningocele and 11multiple sclerosis. At 3 months the mean cystometric bladder capacity increased from 272 ml to420 ml, mean maximal voiding pressure decreased from 61 to 30 cm water and mean bladdercompliance increased from 32 to 72 ml/cm H2O. Of the 180 incontinent patients 132 reportedcomplete continence after treatment, while 48 reported improvement but some level of continu-ing incontinence. Anticholinergic medication could be “considerably reduced” in 118 patientsbut discontinued entirely in only 45. The duration of induced changes was 9 months or more.There were no injection related complications or toxin related side effects reported.Dykstra and Sidi were actually the first to report the use of botulinum toxin type A for striated

sphincter dyssynergia.1 The duration of response that Dykstra et al report here with BTX-B isconsiderably less than that reported with BTX-A. Citing differences in the technique of injectionthey used from that used for BTX-A, the authors believe that further trials to evaluate theefficacy and safety of BTX-B versus BTX-A are warranted. However, with the progressive trackrecord of BTX-A it may be difficult to make a compelling case for such studies.

Alan J. Wein, M.D.1. Dykstra, D. D. and Sidi, A. A.: Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a

double-blind study. Arch Phys Med Rehabil, 71: 24, 1990

Antimuscarinics for Treatment of Overactive Bladder

K. E. ANDERSSON, Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden

Lancet Neurol, 3: 46–53, 2004

For many years, antimuscarinic drugs have been the first-line pharmacological treatment for urgency,frequency, and urge incontinence, all symptoms of the disorder termed overactive bladder. Antimuscarinictreatment is not always effective and is associated with side-effects that limit its clinical use. The clinicalsignificance of the effects of antimuscarinic drugs has been questioned lately. In this review, the rationalefor the use of these drugs in the management of overactive bladder is re-examined and the results oftreatment are discussed. I conclude that these drugs are the only treatment with undisputed effectivenessin the treatment of overactive bladder. They may not be the perfect treatment for all patients with thisdisorder, but their value for individual patients should not be underestimated. Further clinical trials withimprovement in quality of life as the primary endpoint are needed and may give a fair reflection of theclinical value of antimuscarinic drugs.

Editorial Comment: This is the best single short review on the subject that exists. The 80carefully chosen references supplement the extremely well written text. Anyone interested inthe subject should have this article readily available.

Alan J. Wein, M.D.

Randomized, Double-Blind Placebo- and Tolterodine-Controlled Trial of the Once-Daily Anti-muscarinic Agent Solifenacin in Patients With Symptomatic Overactive Bladder

C. R. CHAPPLE, T. RECHBERGER, S. AL-SHUKRI, P. MEFFAN, K. EVERAERT, M. HUANG AND A. RIDDER ON BEHALF

OF THE YM-905 STUDY GROUP, Royal Hallamshire Hospital, Sheffield, United Kingdom, Akademia Med-cyzna Lublinie, Lublin, Poland, St. Petersburg Pavlov Medical University, St. Petersburg, Russia, Round-hay Medical Centre, Nelson, New Zealand, University of Ghent, Ghent, Belgium, Yamanouchi GroupBusiness LLC, Paramus, New Jersey, and Yamanouchi Europe B.V., Leiderdorp, The Netherlands

BJU Int, 93: 303–310, 2004

OBJECTIVE To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral anti-muscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactivebladder (OAB)) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patientswith symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assessthe safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with toltero-dine 2 mg twice daily.PATIENTS AND METHODS The study was an international, multicentre, randomized, double-blind,

tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for�3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomizedequally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency,incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volumevoided/void.RESULTS In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated

for efficacy. Compared with placebo, the change from baseline (�1.41, �32.7%) in the mean number of

VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY 1211

urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (�2.85, �51.9%) and10 mg (�3.07, �54.7%; both P �0.001), but not with tolterodine (�2.05, �37.9%; P � 0.0511). There was astatistically insignificant decrease in episodes of incontinence with tolterodine (�1.14; P � 0.1122) but asignificant decrease in patients treated with solifenacin 5 (�1.42; P � 0.008) and 10 mg (�1.45; P � 0.0038).Compared with placebo (�1.20, �8.1%) the mean number of voids/24 h was significantly lower in patientsreceiving tolterodine (�1.88, �15%; P � 0.0145), solifenacin 5 (�2.19, �17%) and 10 mg (�2.61, �20%; bothP �0.001). The mean volume voided/void was also significantly higher with all three active treatments(P �0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most commonside-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and21.3% receiving 10 mg solifenacin.CONCLUSION Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and

was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated signifi-cantly favourable efficacy to side-effect ratio in treating symptomatic OAB.

Darifenacin, anM3 Selective Receptor Antagonist, is an Effective andWell-Tolerated Once-DailyTreatment for Overactive Bladder

F. HAAB, L. STEWART AND P. DWYER, Departement d’Urologie, Hopital Tenon, Paris, France, Western General,Edinburgh, Scotland, United Kingdom, and Mercy Hospital for Women, Melbourne, Australia

Eur Urol, 45: 420–429, 2004

Objectives: To evaluate the efficacy, tolerability and safety of darifenacin, a once-daily M3 selectivereceptor antagonist (M3 SRA), in patients with overactive bladder (OAB).Methods: This multicentre, double-blind, placebo-controlled, parallel-group study enrolled 561 patients

(19–88 years; 85% female) with OAB symptoms for �6 months, and included some patients with priorexposure to antimuscarinic agents. After washout and a 2-week placebo run-in, patients were randomised(1:4:2:3) to once-daily oral darifenacin controlled-release tablets (3.75 mg [n � 53], 7.5 mg [n � 229] or 15mg [n � 115]) or matching placebo (n � 164) for 12 weeks. Patients recorded daily incontinence episodes,micturition frequency, bladder capacity (mean volume voided), frequency of urgency, severity of urgency,incontinence episodes resulting in change of clothing or pads and nocturnal awakenings due to OAB usingan electronic diary during weeks 2, 6 and 12 (directly preceding clinic visits). Tolerability data wereevaluated from adverse event reports.Results: Darifenacin 7.5 mg and 15 mg had a rapid onset of effect, with significant improvement

compared with placebo being seen for most parameters at the first clinic visit (week 2). This effect wassustained through week 12. At this time the number of incontinence episodes per week was reducedfrom baseline by 67.7% with darifenacin 7.5 mg and 72.8% with darifenacin 15 mg compared with 55.9%with placebo (p � 0.010 and p � 0.017, respectively, versus placebo). The 3.75 mg group (null dose arm)was included for proof of concept of dose flexibility, therefore formal sample sizing and statisticalanalysis were not performed for this group.Darifenacin 7.5 mg and 15 mg, respectively, were significantly superior to placebo for improvements in

micturition frequency (p �0.001, p �0.001), bladder capacity (p �0.040, p �0.001), frequency of urgency(p �0.001, p � 0.005), severity of urgency (p �0.001, p � 0.002) and number of incontinence episodes leadingto a change in clothing or pads (p �0.001, p � 0.002). There was no significant reduction in nocturnalawakenings due to OAB. The most common adverse events were mild-to-moderate dry mouth and consti-pation. However, no patients withdrew from the study as a result of dry mouth and discontinuation relatedto constipation was rare (0.6% placebo versus 0.9% darifenacin). In addition, there was a low need forlaxative use, with no difference between the darifenacin groups and those taking placebo. There were noreports of blurred vision and the CNS and cardiac safety profile was comparable to placebo.Conclusions: Darifenacin significantly improves the major symptoms of OAB. No significant CNS (pri-

marily M1-receptor mediated) adverse events or cardiac (primarily M2-receptor mediated) adverse eventswere identified in this study, as may be predicted from the M3 selective receptor profile of darifenacin.

Uroselectivity: End of the Road?

M. G. WYLLIE, Urodoc, Herne Bay, Kent, United Kingdom

BJU Int, 92: 141–142, 2003

No Abstract

Editorial Comment: Solifenacin and darifenacin are 2 drugs that are currently awaitingapproval by the Food and Drug Administration for the treatment of overactive bladder in theUnited States. Both drugs were compared against placebo and solifenacin was compared as wellagainst tolterodine, although a twice daily formulation was utilized instead of the once dailypreparation most commonly used at present (because at the time the study was done, the oncedaily was not available). The efficacy of the drugs, using standard outcome parameters, is, in myopinion, little different from the once daily or patch preparations already on the market in theUnited States. The drugs have different spectra of side effects, and those who are interested

VOIDING FUNCTION, BLADDER PHYSIOLOGY AND PHARMACOLOGY, AND FEMALE UROLOGY1212