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Overactive bladder: conservative and

medical treatment
Definition
OAB is a symptom syndrome defined as urgency, with or without urge in-
continence, usually with frequency and nocturia. It is caused by detrusor
overactivity. Seventeen per cent of the population aged >40y in Europe
have symptoms of OAB.1 The prevalence increases with age.
Conservative management
Supervised PFMT for 3 months for women is beneficial. Biofeedback and
electrical stimulation therapy can complement PFMT by helping women
become more aware of the pelvic floor muscles. Behavioural modifica-
tion involves modifying fluid intake, avoiding bladder irritants (caffeine, al-
cohol, fizzy drinks), and bladder training for 6 weeks (delayed micturition
for increasing periods of time by inhibiting the desire to void). If this fails,
consider medication.
Anticholinergic medication
Acetylcholine acts on muscarinic receptors (M3 ± M2 subtypes) on the
bladder smooth muscle (detrusor) to cause involuntary contractions and
provoke the symptoms of bladder overactivity. These receptors are the tar-
gets of anticholinergic (antimuscarinic) drugs which inhibit contractions and
increase bladder capacity. 750% of patients will benefit from medication.
• Oxybutynin: mixed action (antimuscarinic, LA, and direct muscle
relaxation). It is available as immediate-​or extended-​release (ER)
tablets, transdermal patch and gel preparations, and can be given
intravesically. It is effective but has a high rate of side effects, reducing
patient compliance. NICE recommends this as a first-​line drug
treatment.2
• Solifenacin: selective antimuscarinic antagonist (M3 > M2). The
STAR trial3 compared solifenacin to tolterodine ER and found higher
improvements in urgency, urge incontinence, and overall incontinence
with solifenacin (59% became continent vs 49%). The number of
patients discontinuing treatment due to side effects was similar
(3–​3.5%).
• Tolterodine: bladder-​selective antimuscarinic, metabolized to 5-​
hydroxymethyl tolterodine (5-​HMT). ER formulation has demonstrated
good efficacy and tolerability.4 NICE recommends this as a first-​line drug
treatment.2
• Fesoterodine: non-​selective antimuscarinic with 5-​HMT active
metabolite. Superior to tolterodine in reducing urgency, improving
bladder capacity and continence (64% dry vs 57% with tolterodine),
with the added benefit of a flexible dosing regimen.5
• Darifenacin: highly selective M3 antagonist. Achieves significant
reduction in urinary frequency, urgency, incontinence episodes (77%
with 15mg dose).6 It is well tolerated (2.1% discontinued 15mg
treatment due to side effects). NICE recommends this as a first-​line
drug treatment.2
Overactive bladder: conservative and medical treatment 163

• Trospium: non-​selective for muscarinic receptors. Minimal passage

across the blood–​brain barrier, with the theoretical benefit of fewer
cognitive effects. ER formula has good long-​term results.7
• Propiverine: non-​selective for muscarinic receptors.
Contraindications to anticholinergics
• Uncontrolled narrow-​angle glaucoma, myasthenia gravis, bladder
outlet obstruction, bowel disorders (i.e. active ulcerative colitis, bowel
obstruction).
Common side effects of anticholinergics
• Dry mouth, constipation, blurred vision, urinary retention, cognitive
impairment, skin rash with transdermal patches.
Anticholinergic burden
Consideration should be taken for the number of drugs with anticholin-
ergic effects that a patient is already taking, and try to rationalize medi-
cation where possible or use lower doses. This is particularly important
in >65y olds. Drugs with the highest anticholinergic effects are bladder
antimuscarinics, antihistamines, and antidepressants. An assessment tool—​
the anticholinergic Cognitive Burden Scale—​can help produce a score for
individual patients at risk. While controversial, there is some evidence that
higher chronic exposure to anticholinergic drugs may adversely affect cog-
nitive function and potentially contribute to dementia.8
Mirabegron (Betmiga®)
β3-​adrenoceptor agonist drug. Causes smooth muscle relaxation by redu-
cing muscle sensitivity to calcium and can improve bladder storage without
affecting contraction of the bladder. NICE currently recommends its use
in patients in whom antimuscarinic drugs are contraindicated or clinically
ineffective or have unacceptable side effects.9 Mirabegron reduces incon-
tinence episodes by 34% and urinary frequency by 44%, as compared to
placebo, after 3 months of treatment,10 and effects appear durable up to
1y.11 A reduced dose (25mg ER) should be given in renal and liver impair-
ment. Contraindication: severe, uncontrolled high BP (>180mmHg systolic
and >110mmHg diastolic). Side effects: tachycardia, UTI, and atrial fibrilla-
tion (AF) (rare). Also refer to the British National Formulary (BNF).
Combination therapy
Due to the different mechanisms of action, it is feasible to combine
mirabegron with anticholinergic medication in patients who have failed
to obtain optimal effect with monotherapy alone. Although this is not
yet licensed, safety has been demonstrated in trials. Solifenacin 5mg, in
combination with mirabegron 50mg ER, demonstrated improvements in
micturition frequency and incontinence episodes, compared to solifenacin
monotherapy, with no episodes of urinary retention.12
Other drugs used for OAB
• Topical oestrogen: can improve urgency, urgency incontinence,
frequency, and nocturia in post-​menopausal women.13 Relative
contraindication is a history of breast or uterine cancer.
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References
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