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Treatment of Overactive Bladder
was overshadowed by the higher incidence of severe cases of dry up, improvement over pre-treatment levels was still evident in daily
mouth: 30% with oxybutynin ER against 22% with tolterodine ER.
7
frequency, incontinence and urgency episodes. However, 20% of the
Solifenacin 5 or 10mg and tolterodine ER 4mg once a day were patients required prolonged, clean, intermittent catheterisation to
compared in a 12-week trial. The majority of side effects were mild to evacuate the bladder.
moderate in nature, and discontinuations were comparable and low in
both groups. Solifenacin, with a flexible dosing regimen, showed greater Fewer cases of urinary retention were reported by Schmid et al. with
efficacy than tolterodine in decreasing urgency episodes, incontinence, detrusor injections of only BoNT-A 100U.
23
In 100 OAB patients
urgency incontinence and pad usage. However, the difference between with idiopathic detrusor overactivity, the neurotoxin completely
the mean baseline to end-point changes between the two arms were abolished incontinence and urgency in 86 and 82% of patients,
very small in absolute terms.
16
Another study concluded that trospium respectively, during an average period of six months. Only 4%
chloride 20mg BID and oxybutynin IR 5mg BID offered similar reductions experienced temporary urinary retention, although an additional
in frequency, incontinence and episodes of urgency. However, trospium 15% reported moderate voiding difficulties. Whether 100U of BoNT-A
chloride showed a slightly better tolerability.
4
will become the ideal dose to treat OAB patients with detrusor
overactivity refractory to anticholinergic therapy will depend on the
Other antimuscarinic drugs are also under active investigation. confirmation of Schmid’s results by forthcoming clinical trials. In
Propiverine has combined antimuscarinic and calcium channel blocker addition, it is unclear whether BoNT-A is useful in OAB patients
activities. It has been used for years in some countries, but long-term without detrusor overactivity.
studies in OAB patients are still anticipated. Darifenacin was shown to
be superior to placebo in 7.5 and 15mg doses in phase III clinical The ideal place to inject the neurotoxin – the detrusor or the
studies,
17
with rates of discontinuation below 2%. Fesoterodine has suburothelium – has been a matter of debate. Suburothelium
been the subject of reports in international meetings.
18
It is, therefore, injections would target preferentially sensory fibres and could,
probable that in the near future the number of antimuscarinic drugs therefore, reduce the risk of urinary retention. However, studies
licensed for OAB treatment will increase significantly. carried out by Kuo et al.
24,25
could not detect any substantial
differences between the two methods of application in terms of
The prevalence of OAB symptoms increases with age. Therefore, clinical efficacy and rate of urinary retention.
although most OAB studies have enrolled only women, it is reasonable
to expect that elderly male patients will also benefit from treatment of Other Compounds and Targets Under Active Investigation
OAB symptoms. However, there are legitimate concerns about the risk The transient receptor potential vanilloid type 1 (TRPV1), previously
of urinary retention if these men, eventually suffering with benign known as vanilloid receptor, is essential to bladder hyperactivity in
prostatic enlargement (BPE) and mild to moderate forms of bladder animal models of OAB.
26
A proof-of-concept study used bladder
outlet obstruction (BOO), are put on antimuscarinic therapy. instillation of resiniferatoxin (RTX 50nmol/l) to desensitise TRPV1 in a
Exploratory studies with tolterodine indicate that such concerns are selected group of patients with idiopathic detrusor overactivity. RTX
probably exaggerated.
19,20
improved volume to first involuntary detrusor contraction and
decreased urinary frequency and urgency incontinence for more than
The same conclusion was reached by a large, randomised clinical trial three months.
27
that assigned men above 40 years of age with moderate to severe
lower urinary tract symptoms to receive placebo (n=222), 4mg of These results were confirmed in a recent randomised clinical trial
tolterodine ER (n=217), 0.4mg of tamsulosin (n=215) or both involving 54 patients with idiopathic detrusor overactivity. Three
tolterodine ER plus tamsulosin (n=225) for 12 weeks. The incidence of months after treatment, the RTX group had a significantly higher
urinary retention was below 0.5% in all arms. Interestingly, the percentage of patients with excellent and improved results compared
combination of tolterodine ER with tamsulosin proved to be the most with the control group. At six months, treatment remained effective in
effective treatment.
21
half of the patients in the RTX group but in only 10% of the control
group.
28
The easy administration and long-lasting effect of RTX makes
In spite of these data, it is still too soon to make a definitive statement the compound attractive for OAB treatment.
about the clinical benefit and safety of antimuscarinics in the elderly
male population with OAB symptoms. Adrenergic nerves extensively innervate the human bladder and both
alpha- and beta-adrenergic receptors have been identified in the
Botulinum Toxin Subtype A organ. The latter predominate in the bladder body and their
There has been great interest in recent years in the intravesical application stimulation induces relaxation of the human bladder.
29
Two
of botulinum toxin subtype A (BoNT-A) for the treatment of OAB compounds, YM-178 and GW-427353, have undergone clinical trials.
symptoms refractory to antimuscarinic drugs. The symptomatic relief Preliminary reports indicate that YM-178 improves urgency, urgency
found in a high percentage of patients was long-lasting – a clear incontinence and urinary frequency in OAB patients.
advantage in terms of persistence on treatment. It should, however, be
recalled that bladder application of BoNT-A remains an off-label procedure The neurokinins (NKs), such as substance P and NKA and B, are a
and is considered an experimental procedure in many countries. family of neuropeptides that are widely distributed in the human
bladder.
30
NK-containing sensory fibres are increased in the bladder of
Popat et al.
22
applied BoNT-A 200U by detrusor injections in 31 OAB patients
30
and both NK1 and NK2 receptor antagonists were
patients with idiopathic detrusor overactivity. At four-month follow- shown to increase bladder capacity in several animal models of bladder
EUROPEAN GENITO-URINARY DISEASE 2007 43
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