© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
6
Radomski AND Barkin
The benefit of bladder retraining is that it is relatively
harmless. The disadvantages are that it is time
consuming, there are no set protocols, results can be
variable, trained therapists are oftennot readily available,
and it can be costly.
Pharmacotherapy
In all instances, pharmacotherapy should be added
to conservative and behavioral treatment. The best
results occur when both pharmacotherapy and
behavioral treatment are initiated.
16
The main first-line medications for the treatment of
OAB are anticholinergics (antimuscarinics). Hormone
replacement therapies, tricyclic antidepressants,
desmopressin, alpha blockers, and Botox injections
have been used in certain cases.
Anticholinergics (antimuscarinics)
These are the mainstays of OAB treatment. The
recommendations for their use are based on level 1,
grade A evidence.
17
Numerous randomized placebo-
controlled trials have confirmed the effectiveness
of these drugs for OAB.
18-26
Most anticholinergics
have very similar side effects, which include dry
mouth, constipation, and dry eyes, see Table 5.
Cognitive impairment is also of concern with some
anticholinergic medications. Trospium (Trosec),
solifenacin (Vesicare), and darifenacin (Enablex) do not
appear to affect cognitive function.
24,27,28
Immediate-
release and long-acting forms of oxybutynin have been
shown to cause cognitive impairment.
29,30
Cognitive effects of tolterodine appear to be low,
due to the relatively low lipophilicity of this drug,
which suggests that it has a limited, though small
ability to penetrate into the CNS.
31
Thus it should be
used with caution in elderly patients who have any
cognitive deficit. Fesoterodine (Toviaz) also appears
to have little effect on cognition in the elderly.
32
Both
fesoterodine and tolterodine (Detrol) are metabolized
to the active metabolite 5-hydroxymethyl tolterodine
(5-
HMT). However, tolterodine undergoes this
conversion in the liver, whereas fesoterodine is
converted by serum esterases, bypassing the liver.
Thus, more reliable, consistent, and tighter therapeutic
blood levels can be achieved with fesoterodine. The
two drugs have virtually identical side-effect profiles
at dosages of 4 mg. However, whereas in patients who
do not respond to 4 mg of fesoterodine, dosages can
be safely and effectively escalated to 8 mg, doubling
the tolterodine dosage is contraindicated.
33
In addition to the above-mentioned anticholinergics,
which are in pill form, a long-acting oxybutynin topical
gel (Gelnique) is now available. Because it is topical, it
is not first metabolized through the liver, so it is safer
in individuals who have any liver deficiency. In a 1
week randomized controlled study in healthy older
adults, oxybutynin topical gel didnot have any clinically
meaningful effect on recent memory or other cognitive
functions.
34
As well, the topical formhas been reported
to be associated with a lower incidence of dry mouth
and constipation.
For more information about these newer
anticholinergic therapies—fesoterodine andmirabegron
(
a selective, human beta- 3 adrenoreceptor agonist)—
see the “Emerging Therapies” article by Barkin in this
supplement.
35
The effect of combining anticholinesterase drugs
used for cognitive impairment with anticholinergic
drugs for OAB is currently unclear.
36
The combination
should be usedwith caution. The use of anticholinergics
in older menwith OAB is a special situation, since BPH
may play a role. Good evidence suggests that the use of
an alpha blocker and an anticholinergic can significantly
improve LUTS in men with BPH.
37
However, it is
important tomake sure thesemen empty their bladders
more completely and effectively, since urine retention,
although not as common as once believed, can occur in
older men who are taking anticholinergics.
Hormone replacement therapy
The use of hormone replacement therapy (including
estrogen in oral or cream form) should be considered
for women with genitourinary atrophy, but this
therapy has little effect on decreasing incontinence.
38
Tricyclic antidepressants
These have been used to treat OAB, but they are not
first-line therapies. The exact mechanism by which
they affect the bladder is unclear.
39
They are effective
and have been used extensively to treat bedwetting in
children.
40
They should be used with caution in the
elderly, since they can cause confusion, drowsiness,
and arrhythmias.
41,42
Desmopressin
This oral, synthetic antidiuretic hormone, has been
extensively used in children for nocturnal enuresis.
43
Desmopressin works to reduce urine production by
increasing water reabsorption in the renal collecting
ducts for up to an average of 10 hours. It is not first-
line therapy for nocturia in adults, but it can be used
to treat some adults. In elderly patients, however, the
drug can cause hyponatremia that leads to congestive
heart failure.
44,45
Therefore, the use of desmopressin is
not generally recommended in the elderly.
