EURURO Vol. 72 No. 5

763 860

0.46 episodes (LoE 2b) . Solifenacin 5 mg and 10 mg
increased night-time volume voided per micturition by
30 ml and 41 ml (p = 0.0033 and p < 0.0001, respectively).
Propiverine was not superior to placebo in reducing
nocturia frequency (p = 0.471; LoE 1b) . Similar results
were seen from another placebo controlled trial which
compared propiverine versus solifenacin (LoE 1b) Only
solifenacin 10 mg resulted in statistically significant reduc-
tions in the number of nocturia episodes versus placebo
(p = 0.021).
Adverse events attributable to antimuscarinic medica-
tions (eg, dry mucous membranes, constipation, gastro-
esophageal reflux) have been extensively reported in OAB,
and there is no suggestion that they differ in a population of
patients with nocturia.
3.3.3. Beta-3 agonist
Data from a phase 2 dose-ranging study of mirabegron in a
mixed population with OAB, showed that mirabegron
50 mg reduced nocturia episodes by 0.6 from baseline (vs
0.22 on placebo, p < 0.05; LoE 1b) Adverse events
attributable to mirabegron (eg, hypertension) have been
reported in OAB studies.
3.3.4. 5-a reductase inhibitors (alone or in combination)
Pooled data from dutasteride phase 3 studies looking at
results of IPSS Question 7 has been reported for
4321 patients (LoE 1b) . Improvements in overall
nocturia parameters were superior with dutasteride versus
placebo from 12 mo onwards. The largest treatment group
differences were seen in patients with a baseline nocturia
score of 2 or 3.
A post-hoc subgroup analysis of self-reported nocturia in
the Medical Therapy of Prostatic Symptoms trial of men
with LUTS (LoE 1b) found mean nocturia was reduced
by –0.35, –0.40, –0.54, and –0.58 in the placebo, finasteride,
doxazosin, and combination groups at 1 yr. Reductions with
doxazosin and combination therapy, but not finasteride,
were greater than with placebo at 1 yr and 4 yr.
A secondary analysis of the Veterans Affairs Cooperative
Study Program Trial reported on 1078 men (LoE 2b)
. From a baseline mean of 2.5, nocturia decreased to
1.8, 2.1, 2.0, and 2.1 in the terazosin, finasteride, combina-
tion, and placebo groups, respectively. Of men with 2
episodes of nocturia, 50% reduction was seen in 39%, 25%,
32%, and 22%.
Adverse events attributable to 5-a reductase inhibitors
(eg, reduced ejaculate volume and effects on prostate-
specific antigen) have been extensively reported in male
voiding LUTS patients, and there is no suggestion that they
differ in a population of patients with nocturia.
3.3.5. PDE5 inhibitor
Separately, individual studies using tadalafil did not show
significant improvement in nocturia. An analysis of four
registrational RCTs of tadalafil for LUTS evaluated pooled
responses to IPSS Question 7 (LoE 1b) Overall severity
of nocturia was 2.3 1.2, and the mean treatment change
was –0.4 with placebo and –0.5 with tadalafil. Improved
nocturnal frequency was seen in 47.5% on tadalafil (41.3% with
placebo), and worse in 11.5% (vs 13.9%), which was not
considered clinically meaningful.
Adverse events attributable to PDE5 inhibitors have been
extensively reported in erectile dysfunction patients, and
there is no suggestion that they differ in a population of
patients with nocturia.
3.4. Other medications
3.4.1. Diuretics
Administration of a diuretic in the afternoon has been
proposed to reduce salt and water load in the body prior to
bedtime. A double blind RCT compared diuretic therapy
(azosemide 60 mg) against diazepam (5 mg) in 51 patients
(47 men) with nocturia 3/night and no daytime urological
problems (LoE 2b) . For people with a higher atrial
natriuretic peptide at baseline, daytime diuretic decreased
the nocturnal frequency. Diazepam decreased nocturia in
22 out of 29 patients.
The efficacy of 1 mg bumetanide was evaluated in an RCT
of 28 patients (15 men) in general practice (LoE 2b)
. During the placebo period the weekly number of
nocturia episodes was 13.8 and during bumetanide
treatment the number was reduced by 3.8. Ten men with
BPE did not improve with bumetanide.
An RCT of 49 men with nocturnal polyuria evaluated
furosemide 40 mg given 6 h before sleep (LoE 1b) ,
yielding a decrease of 0.5 voids/night, versus 0 for placebo.
Another study reported a strategy of furosemide and
desmopressin for nocturia ( 2 voids/night) in the elderly
(LoE 1b) Eighty-two patients (58 men) were random-
ized to receive furosemide (20 mg, 6 h before bedtime) and
the individual’s optimal dose of desmopressin (at bedtime)
or placebo for 3 wk. Reduced nocturnal voids (3.5 vs 2.0,
p < 0.01) and urine volume (920 ml vs 584 ml, p < 0.01)
were observed with active treatment.
Some diuretics work by causing natriuresis, and hence
may be contraindicated in patients with hyponatremia, or
at risk of acquiring it.
3.4.2. Nonsteroidal anti-inflammatory drugs
Diclofenac taken in the late evening was evaluated in
nocturnal polyuria . Twenty-six patients (20 men, mean
age 72 yr) received 2 wk of placebo or active medication,
crossing-over following a 1-wk rest period. Nocturia
decreased from 2.7 to 2.3 (p < 0.004). An RCT of celecoxib
100 mg versus placebo was undertaken in 80 men with BPE
and 2 nocturia/night (LoE 1b) . In the celecoxib group,
mean nocturnal frequency decreased from 5.2 to 2.5 com-
pared with 5.3 to 5.1. No significant side effects were
reported in either study.
Tamsulosin (0.4 mg) alone or combined with meloxicam
(15 mg), have been compared in 400 men with LUTS and
nocturia (LoE 1b) . Total IPSS, IPSS-Quality of Life,
nocturia, and sleep quality score were significantly lower
with combination therapy. A RCT randomized 40 men to
loxoprofen, a-blocker, and 5-a-reductase inhibitors
(vs a-blocker and 5-a-reductase inhibitors; LoE 2b)
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