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Treatment of Overactive Bladder
a report by
and Francisco Cruz
1. Consultant Urologist; 2. Professor and Chairman of Urology, Hospital S João/Faculty of Medicine, Porto
Overactive bladder (OAB) is urgency, with or without urgency Tolterodine was the first antimuscarinic agent claiming high selectivity
incontinence, that is very often accompanied by frequency and for bladder tissue. In a 12-month open-label extension of four
OAB is a chronic disease that affects more than 10% of randomised, placebo-controlled trials, 61% of 714 patients receiving
adults of both genders in the Western world.
Pharmacological tolterodine IR 2mg BID completed the treatment. However, dosage
management of OAB patients is usually initiated with antimuscarinic reduction to 1mg twice daily was required in 23% of patients.
drugs. For patients refractory to this therapy, botulinum toxin subtype Introduction of tolterodine ER undoubtedly improved persistence on this
A (BoNT-A) is now being offered as an off-label treatment. In this drug. In fact, 71% of the 1,077 patients completed a 12-month open-
review both substances will be examined. Particular emphasis will be label study with tolterodine ER.
This should be attributed to the fact
placed on the persistence rates observed during prolonged that tolterodine ER is at least as effective as IR formulations in reducing
antimuscarinic therapy. Persistence rate is the balance between drug OAB symptoms, but triggers fewer autonomic adverse effects.
efficacy and tolerability and the expectations of patients, and strongly
influences the percentage of OAB patients who will obtain maximal Trospium chloride is a quaternary ammonium derivative. Such
benefit from drug treatment. In addition, some areas of active molecular configuration reduces transport across the blood–brain
investigation on OAB pharmacotherapy will be briefly reviewed. barrier and may diminish the incidence of cognitive side effects. In a
52-week trial involving 357 individuals with OAB in which trospium
Antimuscarinic Drugs 20mg BID was randomised against oxybutynin IR 5mg BID, 75% of the
Oxybutynin is the oldest antimuscarinic drug in use for the treatment of patients in the trospium arm completed the study.
OAB symptoms. Nevertheless, severe side effects associated with its
chronic administration make the persistence on oxybutynin very low. Solifenacin succinate was the first M3-specific antimusacarinic drug to
Fewer than 20% of women with OAB symptoms persisted on the reach the market. In double-blind, randomised, placebo-controlled
medication six months after starting oxybutynin immediate-release (IR) clinical trials, this compound at 5–10mg per day significantly reduced
5mg total integrated dose (TID).
Persistence on oxybutynin IR may all OAB symptoms, including urgency,
and improved quality of life
possibly improve by reducing the daily dose to 5mg twice a day (BID) while (QoL).
In a 52-week open-label study, 81% of the 1,637 patients
still maintaining a reasonable clinical efficacy.
Nevertheless, the enrolled completed the study. Such a good performance was
introduction of oxybutynin extended-release (ER) formulations rendered associated with a low rate of autonomic side effects. Only 4.7% of
oxybutynin IR almost obsolete. Oxybutynin ER is as effective as oxybutynin patients discontinued treatment owing to severe antimuscarinic
IR for controlling OAB symptoms while inducing fewer adverse autonomic events. Interestingly, long-term exposure to solifenacin was associated
Accordingly, the persistence rate on oxybutynin 10mg ER in a with an incremental improvement in the cure rate of incontinence,
12-month open-label trial including 1,067 patients was 46%.
urgency and urinary frequency.
A note of caution should probably be made at this point. Clinical trials
Carlos Silva is a Consultant Urologist at the Hospital S João/
Faculty of Medicine of Porto, Portugal. He underwent
do not necessarily reflect everyday clinical practice and persistence
clinical training in urology with Professor Francisco Cruz rates of OAB patients on prolonged antimuscarinic treatment may be
and in 2000 initiated a research programme on vanilloid
much lower than actually suggested in the previous studies. In a recent
compounds for the treatment of detrusor overactivity in
order to obtain his PhD.
analysis, based on the number of purchases made by almost 20,000
OAB patients prescribed with oxybutynin or tolterodine IR or ER, it was
estimated that after one year patients still taking the medication did
not exceed 20%.
Francisco Cruz is a Professor of Urology and Chairman of
Urology in Hospital S João/Faculty of Medicine of Porto,
Portugal. He is the leader of an active group of researchers A recent systematic review and meta-analysis suggested that clinical
who investigate the contribution of bladder sensory input
effectiveness between individual drugs is also different.
In order to
to the appearance of lower urinary tract symptoms in
several diseases, including overactive bladder, chronic
better appreciate such differences, head-to-head trials are now being
bladder inflammation and bladder outlet obstruction. He is
pushed forwards, but the results are still inconclusive. Tolterodine ER
a member of the Scientific Committee of the European
Association of Urology (EAU) and has supervised the
4mg and oxybutynin ER 10mg were compared in a 12-week study
clinical training of a large number of urologists. including 790 women with OAB symptoms. Interestingly, there was a
small advantage for oxybutynin ER in the resolution of frequency and
urgency incontinence. However, the small superiority of oxybutynin ER
42 © TOUCH BRIEFINGS 2007