EURURO Vol. 72 No. 5

761 860

1b) . Nocturia severity was around 3 episodes/night,
and 90% of patients had nocturnal polyuria. Increasing
doses of desmopressin were associated with decreasing
numbers of nocturnal voids and voided volume, greater
responder rates, and increased first sleep period duration.
Reductions in serum sodium to <125 mmol/l occurred in
two men taking 100 m g desmopressin. A 3-mo RCT reported
on desmopressin orally disintegrating tablets or placebo in
385 men with 2 nocturnal voids (LoE 1b) . Fifty
micrograms (–0.37) and 75 mg (–0.41) desmopressin
reduced the number of nocturnal voids, and increased
the time to first void by approximately 40 min. Two patients
on 50 mg desmopressin and nine on 75 mg developed a
serum sodium level <130 mmol/l. A separate study in Japan
reported similar findings (LoE 1b) .
Intranasal administration was trialed in 20 men with
nocturnal polyuria in a short-term cross-over RCT compar-
ing placebo or 20 mg desmopressin, followed by an open
period with 40 mg desmopressin (LoE1b) . Desmopres-
sin reduced nocturnal urine volume and the percentage of
urine passed at night. However, the reduction in nocturnal
frequency was only significant during unblinded treatment
with 40 m g desmopressin.
3.3. Medications to treat LUTD
3.3.1. Selective a -1 adrenergic antagonists
An 8-wk study assessed tamsulosin (oral controlled
absorption system formulation) in men (aged > 45 yr,
International Prostate Symptom Score [IPSS] > 13, maxi-
mum flow rate 4–12 ml/s, and > 2 nocturnal voids; LoE 1b)
. The mean increase in hours of undisturbed sleep was
60 min for placebo and 82 min for tamsulosin (p = 0.198).
The mean reduction in nocturnal voids was –1.1 for
tamsulosin (–0.7 for placebo, p = 0.099). The mean reduc-
tion in IPSS was 8.0 for tamsulosin (vs 5.6, p = 0.0099). Eight
treatment-emergent adverse events were reported with
tamsulosin, 10 with placebo.
Several studies used a-adrenergic blockade as compara-
tor arms, and these are summarized in . One study
randomized 31 men with benign prostate enlargement
(BPE) and nocturia 3/night to 2 mg doxazosin for 2 wk
increasing to 4 mg, versus 20 mg intranasal desmopressin
. In the doxazosin group, nocturia reduced from 3.2/
night to 1.2/night, versus 3.4–1.5 for desmopressin.
Improvements in nocturia, quality of life and peak flow
rates were not significantly different, while change in IPSS
was better in the doxazosin group. Another trial random-
ized men to receive either naftopidil 50 mg or tamsulosin
0.2 mg (LoE 2b) At 2 wk, patients on naftopidil
significantly improved their nocturia score, but at 8 wk the
results were comparable between the two arms.
A post-hoc subgroup analysis of three pooled studies
using silodosin 8 mg inmenwith LUTS looked at responses to
Question 7 of the IPSS (‘‘How many times did you typically
get up at night to urinate?’’; LoE 1b) More men treated
with silodosin reported nocturia improvement (53% vs 43%,
p < 0.0001) and fewer patients worsening (9% vs 14%,
p < 0.0001). In men with >2 nocturnal voids at baseline,
61% and 49% of patients with silodosin and placebo had
reductions of >1 voids/ night, respectively (p = 0.0003). A
multicenter 12-wk trial randomizedmen to receive silodosin,
tamsulosin, or placebo and found that only silodosin
significantly reduced nocturia versus placebo (p = 0.013)
and the change from baseline was –0.9, –0.8, and –0.7 for
silodosin, tamsulosin, and placebo, respectively (LoE 1b)
An RCT compared tamsulosin versus TURP for nocturia in
66 men with LUTS suggestive of BPE and no other
predisposing factors for nocturia (LoE 2b) . Both
tamsulosin and TURP improved nocturia, with a greater
response seen with TURP in the number of nocturnal
awakenings and in symptom scores.
The combination of desmopressin and tamsulosin is
superior to tamsulosin alone, since it reduces nocturnal
frequency (–1.96 vs –1.41) and increases the first period of
sleep (77.9 min vs 40.6 min), respectively (LoE 2b) . The
add-on of mirabegron to tamsulosin significantly improved
IPSS Question 7 score from baseline compared with
tamsulosin monotherapy (–0.47 vs –0.16, respectively;
LoE 2b) Evidence from the CombAT study suggests that
the combination of dutasteride and tamsulosin is more
efficient at reducing nocturia score compared with tamsu-
losin monotherapy (LoE 1b)
Headache is the most frequent adverse event with
tamsulosin therapy (3.2–5.5%). Dry ejaculation is more
common with silodosin than tamsulosin or placebo (14.2%
vs 2.1% vs 1.1%, respectively, p < 0.001).
3.3.2. Antimuscarinics
A post-hoc analysis of two 12-wk RCTs of tolterodine 4-mg
extended release, evaluated 745 men with 2.5 or more
nocturia episodes/night, using a 7-d diary capturing
urgency scores for each void (LoE 1b) . Tolterodine
significantly reduced the weekly values for night-time
severe OAB micturitions. Adverse events showed a higher
incidence of dry mouth for tolterodine (11% vs 4%). Using
bladder diaries in which each void was attributed as ‘‘non-
OAB’’ or OAB, another study randomized tolterodine
extended release 4 mg against placebo (LoE 1b) . Tolter-
odine reduced OAB-related nocturnal micturitions, but not
the total nocturnal micturitions.
A 3-mo RCT of 963 adults with OAB evaluated
fesoterodine flexible dosing for nocturnal urgency ( 2/
night; LoE 1b) . Change in mean number of nocturnal
urgency episodes ( 1.28 vs 1.07) and nocturnal micturi-
tions (–1.02 vs –0.85) was greater with fesoterodine than
placebo. A separate post-hoc analysis of a 12-wk RCT
studied 555 Asian adults with 2 nocturia, 8 voiding, and
1 urgency urinary incontinence episodes/24 h (LoE 2b)
. Reductions in nocturia were not significantly different
(fesoterodine 4 mg –0.63, 8 mg –0.77, vs placebo –0.56).
When patients with a nocturnal polyuria index >33% were
excluded, the decrease in nocturia was significantly greater
with fesoterodine 8 mg verus placebo. Increases in noctur-
nal voided volume/micturition were greater with fesoter-
odine 4 (+38 ml) and 8 mg (+42 ml) than placebo (+15 ml).
Subgroup analysis of data from an RCT of Japanese OAB
patients, showed solifenacin 10 mg decreased nocturia by
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