Treating the Overactive
Bladder – Step by Step
Article contributed by:
Dr Sharon Yeo,
Consultant, Urology
Tan Tock Seng Hospital,
Singapore
for New Dimension -
biannual newsletter of
the
Society for Continence,
Singapore
Living with an
overactive bladder (OAB)
is distressing. It
is common and affects
29.9% of Asian men and
up to 53.1% of women
according to two large
epidemiological surveys
conducted in eleven
Asian countries. The
incidence of OAB
increases with age but
it can affect a person
at any age. It is
encouraging to know that
there is hope for cure
in many patients with
emerging approved
treatments available in
Singapore in the recent
years.
Definition
Patients with OAB
presents with the sudden
need to rush to the
toilet and the fear of
wetting themselves. This
urgency sensation is the
hallmark symptom of OAB.
Patients often also have
urinary frequency and
nocturia. OAB is a
clinical diagnosis, made
after exclusion of
infection or other
obvious pathology.
OAB may lead to
incontinence in some
patients, where urine
leakage is accompanied
or immediately preceded
by urgency (urgency
incontinence).
Aetiology
What causes OAB?
What are risk factors of
developing this problem?
There are many theories
of how the bladder
becomes overactive.
These include neurogenic,
myogenic, and that of
integrative physiology
of the bladder.
The contributing factors
in each patient is
different and unique.
This may account for
difference in treatment
response between
individuals.
Normal urine storage and
voluntary bladder
emptying involve complex
interactions between the
central, peripheral
nervous systems and the
lower urinary tract.
Any interruption in any
of the pathways can lead
to abnormal detrusor
activity.
Therefore, risk factors
for OAB include,
previous cerebrovascular
accident, spinal cord
injury, multiple
sclerosis, diabetes
mellitus etc.
There are patients with
no underlying
neurological conditions
which can account for
their symptoms and they
are termed idiopathic
OAB.
Although the management
of OAB, in general,
follows a stepwise
approach, treatment
still has to be
individualised due to
other co-morbidities.
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Clinical assessment
Urgency, frequency, and
nocturia are common
symptoms in OAB.
Patients may or may not
have incontinence.
There may be voiding
symptoms of poor flow
and dribbling in older
men from a chronically
obstructing prostate.
Lower urinary tract
infection (UTI) or
carcinoma in-situ (CIS)
bladder may cause
similar symptoms as OAB,
making them important
differential diagnoses
and should be screened
and treated accordingly.
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Investigations
Urinalysis is a baseline
investigation to detect
any microscopic
haematuria or evidence
of UTI.
A bladder diary records
times of micturation,
voided volumes, leakages
together with fluid
intake over 3-day
period. It is
useful tool providing an
objective assessment on
severity and directs
treatment. Some
patients feel empowered
in managing their
condition as they
complete their diaries.
Urodynamic study has a
role in evaluating
patients who have failed
conservative or medical
therapy for OAB,
especially when
considering more
invasive treatment
options.
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Management Conservative
The initial management
begins with fluid
advice, such as cutting
down on caffeine and
alcoholic beverages
which can trigger OAB
symptoms. Reducing
fluid intake at night
and near bedtime can
help patients with
nocturia. Patients
can be taught bladder
training. It
involves progressive
small increase in
voiding intervals over a
period of time.
Bladder training is
recommended together
with the other lifestyle
interventions and should
be individualised.
Pelvic floor muscle
training (PFMT) can help
in both men and women.
It increases pelvic
floor muscle
contractility, strength
and decrease detrusor
contraction in patient
in OAB. PFMT may
be augmented with
biofeedback and
electrical stimulation.
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Medical therapy
Oral medication is the
next step in the
management of OAB if
response to conservative
measures is suboptimal.
Antimuscarinics has been
the main medical therapy
for OAB. In adults
with OAB,
antimuscarinics shows
significant improvement
in leakage episodes and
frequency in 24 hours,
and better quality of
life scores compared to
placebo. Common
side effects of
antimuscarinics are dry
mouth, dry eyes,
blurring of vision,
retention of urine and
potential cognitive
impairment.
Uncontrolled close-angle
glaucoma is a
contraindication and
caution has to be
exercised in patients
with impaired gastric
emptying and retention
of urine.
The bladder relaxes
during storage phase
under the activation of
sympathetic system via
stimulation of
β3-adrenoceptors.
New agent such as β3-
adrenoceptor agonists,
which has this distinct
mode of action from
antimuscarinics, has
been approved in
countries such as USA,
UK and Japan for the
treatment of OAB.
It is now available in
Singapore. This
new class of medication
facilitates urine
storage by inducing
detrusor relaxation,
with decrease common
side effects of
antimuscarinics.
Mirabegron, a
β3-adrenoceptors
agonist, is the first in
class to have completed
phase 3 registrational
trials and represents a
new oral agent for
treatment of OAB.
In the first randomized
trial involving 2,444
OAB patients in Canada,
South Africa, Australia
and New Zealand,
mirabegron has
demonstrated safety,
tolerability, and
persistence of effect
over 12 months. In
this trial, when
compared to tolterodine
ER 4 mg, incidence of
dry mouth was more than
three-fold higher in the
tolterodine ER 4 mg
group than observed in
mirabegron treated
patients, and small
increases in pulse rate
and blood pressure were
seen with mirabegron but
did not result in
adverse cardiovascular
events.
There is current
evidence to suggest that
mirabegron appears to be
similar in efficacy to
the antimuscarinics and
has lower rates of dry
mouth than any of these
medications.
Mirabegron may produce
lower rates of
constipation than some
of the anti-muscarinics.
If a patient experiences
inadequate symptom
control and/or
unacceptable adverse
drug events with one
antimuscarinic
medication, then a dose
modification or a
different antimuscarinic
medication or a
β3-adrenoceptor agonist
may be tried.
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Botulinum toxin
injection
When oral therapies have
failed, intradetrusor
injection of botulinum
toxin A is a recommended
treatment for selected
OAB patients.
Botulinum toxin A is a
neurotoxin produced by
gram-positive
Clostridium botulinum.
An acetylcholine release
inhibitor, it inhibits
the release of
acetylcholine from
presynaptic cholinergic
nerve terminals into the
neuromuscular junction.
There are seven
serotypes of botulinum
toxin, A to G.
Botulinum toxin A is
used most clinically,
and for the treatment of
OAB and its associated
urinary incontinence.
Botulinum toxin A
disrupts specific sites
on SNARE protein
SNAP-25, which are
components of synaptic
fusion complex that are
involved in release of
acetylcholine, resulting
in paralysis of muscles.
Botulinum toxin A has
been shown to be
effective within 2 weeks
of injection and
efficacy lasted
approximately 42 weeks
(9 months).
Increase in post-void
residual or retention of
urine is the main
adverse effect, and
patients should be
adequately counselled
prior to treatment that
catheterisation may be
required. Intradetrusor
injection of botulinum
toxin A is performed as
a day surgery, via a
flexible or rigid
cystoscope, under local
or regional anaesthetic.
In one of the largest
randomised control trial
in eight UK centres,
botulinum toxin A has
shown to have
statistically
significant reductions
of voiding frequency,
urgency episodes and
leakages in idiopathic
OAB patients compared to
placebo.
Continence rate was
higher in the botulinum
toxin A group but with
higher rates of UTI and
voiding difficulty
requiring clean
intermittent
catheterization (CIC).
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Posterior tibial and
sacral nerve stimulation
Posterior tibial nerve
stimulation (PTNS)
involves electric
stimulation to the
posterior tibial nerve,
via insertion of a fine
34-G needle above the
medial aspect of ankle,
and then to S2-4 sacral
plexus of the sacral
micturition centre.
It is typically given in
12-weekly treatment
cycles of 30 min each.
Evidence suggests that
PTNS may improve urgency
urinary incontinence in
women who fail or cannot
tolerate antimuscarinic
medication, but is not
more effective than
antimuscarinic.
Its efficacy in men is
currently unclear.
PTNS is recommended in
patients who have failed
behavioral and
pharmacologic therapies.
For patients who are not
suited to behavioral and
pharmacologic therapies,
botulinium toxin A
injection, PTNS, or
neuromodulation may be
offered.
In sacral
neuromodulation or
sacral nerve stimulation
(SNS), the sacral nerve
(S3) is electrically
stimulated via an
electrode connected to a
programmable pulse
generator. It is
believe to stimulate
somatic afferent
inhibition within the
spinal cord, modulating
micturition reflex.
It may also have direct
inhibition of
pathological detrusor
contractions of the
bladder. As with
PTNS, SNS is recommended
as treatment option for
urgency incontinence due
to detrusor overactivity
after failed initial
conservative measures in
both men and women.
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Radical surgery
Bladder augmentation or
detrusor myomectomy are
major surgeries rarely
done nowadays for OAB.
They are only considered
in highly selected
patients if there are
severe distressing
symptoms where all
treatment fails.
Careful consideration is
necessary as potential
risks, and complications
are high, including long
term metabolic
complications and risk
of malignancy.
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New therapies under
development
Lower urinary tract
function involves
complex interactions of
numerous pathways,
creating many potential
pharmacological targets
in OAB treatment. Agents
with activity on
neurotransmitters such
as phosphodiesterase (PDE)
inhibitors,
cyclooxygenase (COX)
inhibitors etc are being
studied for their
clinical potential in
the treatment of OAB.
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Conclusion
OAB is a prevalent
condition affecting both
men and women of all
ages with significant
impact on the quality of
life. Management
is stepwise beginning
with PFMT, behavioural
modifications and
bladder training. Second
line medical therapy
includes antimuscarinics,
or the new option of
β3-adrenoceptors
agonist. If symptoms are
not well-controlled or
patients could not
tolerate medications,
intradetrusor injection
of botulinum toxin A,
PTNS or SNS are
alternatives. As
each patient is unique
with different
underlying
co-morbidities and other
chronic medications,
treatment of OAB has to
be individualised.
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Article contributed by:
Dr Sharon Yeo,
Consultant, Urology
Tan Tock Seng Hospital, Singapore
for New Dimension - biannual newsletter of the
Society for Continence, Singapore
Dated: December 2015
|
The
Society for
Continence,
Singapore
(SFCS) is a
non-profit
organization
that
originated
from the
dedicated
efforts of a
group of
doctors,
nurses and
rehabilitation
therapists
who
recognised
the special
needs of the
incontinent
as far back
as 1988.
The mission
of the
society is
to promote
bladder and
bowel health
and to work
towards a
community
free of the
stigma and
restrictions
of
incontinence.
The society
aims to
disseminate
information
and educate
healthcare
professionals
and the
public on
methods to
promote
urinary &
bowel
continence
and to
promote the
education,
training and
rehabilitation
of the
incontinent
and their
general
interests
and welfare. |
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