Scolaris Content Display Scolaris Content Display

PRISMA flow diagram.
Figures and Tables -
Figure 1

PRISMA flow diagram.

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 3

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.

Comparison 1 Desmopressin versus placebo, Outcome 1 Number of nocturnal voids (short term) (subgroup route).
Figures and Tables -
Analysis 1.1

Comparison 1 Desmopressin versus placebo, Outcome 1 Number of nocturnal voids (short term) (subgroup route).

Comparison 1 Desmopressin versus placebo, Outcome 2 Number of nocturnal voids (intermediate term).
Figures and Tables -
Analysis 1.2

Comparison 1 Desmopressin versus placebo, Outcome 2 Number of nocturnal voids (intermediate term).

Comparison 1 Desmopressin versus placebo, Outcome 3 Major adverse events (short term) (subgroup route and dose).
Figures and Tables -
Analysis 1.3

Comparison 1 Desmopressin versus placebo, Outcome 3 Major adverse events (short term) (subgroup route and dose).

Comparison 1 Desmopressin versus placebo, Outcome 4 Major adverse events (intermediate term).
Figures and Tables -
Analysis 1.4

Comparison 1 Desmopressin versus placebo, Outcome 4 Major adverse events (intermediate term).

Comparison 1 Desmopressin versus placebo, Outcome 5 Duration of first sleep episode (short term).
Figures and Tables -
Analysis 1.5

Comparison 1 Desmopressin versus placebo, Outcome 5 Duration of first sleep episode (short term).

Comparison 1 Desmopressin versus placebo, Outcome 6 Duration of first sleep episode (intermediate term).
Figures and Tables -
Analysis 1.6

Comparison 1 Desmopressin versus placebo, Outcome 6 Duration of first sleep episode (intermediate term).

Comparison 1 Desmopressin versus placebo, Outcome 7 Time to first void (short term) [minutes].
Figures and Tables -
Analysis 1.7

Comparison 1 Desmopressin versus placebo, Outcome 7 Time to first void (short term) [minutes].

Comparison 1 Desmopressin versus placebo, Outcome 8 Minor adverse events (short term).
Figures and Tables -
Analysis 1.8

Comparison 1 Desmopressin versus placebo, Outcome 8 Minor adverse events (short term).

Comparison 1 Desmopressin versus placebo, Outcome 9 Minor adverse events (intermediate term).
Figures and Tables -
Analysis 1.9

Comparison 1 Desmopressin versus placebo, Outcome 9 Minor adverse events (intermediate term).

Comparison 1 Desmopressin versus placebo, Outcome 10 Treatment withdrawal due to adverse event (short term).
Figures and Tables -
Analysis 1.10

Comparison 1 Desmopressin versus placebo, Outcome 10 Treatment withdrawal due to adverse event (short term).

Comparison 1 Desmopressin versus placebo, Outcome 11 Treatment withdrawal due to adverse event (intermediate term).
Figures and Tables -
Analysis 1.11

Comparison 1 Desmopressin versus placebo, Outcome 11 Treatment withdrawal due to adverse event (intermediate term).

Comparison 1 Desmopressin versus placebo, Outcome 12 Number of nocturnal voids (short term) (subgroup dose).
Figures and Tables -
Analysis 1.12

Comparison 1 Desmopressin versus placebo, Outcome 12 Number of nocturnal voids (short term) (subgroup dose).

Comparison 1 Desmopressin versus placebo, Outcome 13 Number of nocturnal voids (short term) (subgroup nocturnal polyuria).
Figures and Tables -
Analysis 1.13

Comparison 1 Desmopressin versus placebo, Outcome 13 Number of nocturnal voids (short term) (subgroup nocturnal polyuria).

Comparison 1 Desmopressin versus placebo, Outcome 14 Number of nocturnal voids (short term) (sensitivity run‐in period).
Figures and Tables -
Analysis 1.14

Comparison 1 Desmopressin versus placebo, Outcome 14 Number of nocturnal voids (short term) (sensitivity run‐in period).

Comparison 1 Desmopressin versus placebo, Outcome 15 Major adverse events (short term) (sensitivity run‐in period).
Figures and Tables -
Analysis 1.15

Comparison 1 Desmopressin versus placebo, Outcome 15 Major adverse events (short term) (sensitivity run‐in period).

Comparison 1 Desmopressin versus placebo, Outcome 16 Number of nocturnal voids (short term) (sensitivity clinical dosage).
Figures and Tables -
Analysis 1.16

Comparison 1 Desmopressin versus placebo, Outcome 16 Number of nocturnal voids (short term) (sensitivity clinical dosage).

Comparison 1 Desmopressin versus placebo, Outcome 17 Major adverse events (short term) (sensitivity clinical dosage).
Figures and Tables -
Analysis 1.17

Comparison 1 Desmopressin versus placebo, Outcome 17 Major adverse events (short term) (sensitivity clinical dosage).

Comparison 2 Desmopressin versus behaviour modification, Outcome 1 Duration of first sleep episode (short term).
Figures and Tables -
Analysis 2.1

Comparison 2 Desmopressin versus behaviour modification, Outcome 1 Duration of first sleep episode (short term).

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 1 Number of nocturnal voids (short term).
Figures and Tables -
Analysis 3.1

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 1 Number of nocturnal voids (short term).

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 2 Quality of life (short term).
Figures and Tables -
Analysis 3.2

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 2 Quality of life (short term).

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 3 Major adverse events (short term).
Figures and Tables -
Analysis 3.3

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 3 Major adverse events (short term).

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 4 Minor adverse events (short term).
Figures and Tables -
Analysis 3.4

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 4 Minor adverse events (short term).

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 5 Treatment withdrawal due to adverse event (short term).
Figures and Tables -
Analysis 3.5

Comparison 3 Desmopressin versus alpha‐blocker, Outcome 5 Treatment withdrawal due to adverse event (short term).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 1 Number of nocturnal voids (short term) (subgroup route and dose).
Figures and Tables -
Analysis 4.1

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 1 Number of nocturnal voids (short term) (subgroup route and dose).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 2 Number of nocturnal voids (short term) (subgroup nocturnal polyuria).
Figures and Tables -
Analysis 4.2

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 2 Number of nocturnal voids (short term) (subgroup nocturnal polyuria).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 3 Quality of life (short term) (subgroup route and dose).
Figures and Tables -
Analysis 4.3

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 3 Quality of life (short term) (subgroup route and dose).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 4 Quality of life (short term) (subgroup nocturnal polyuria).
Figures and Tables -
Analysis 4.4

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 4 Quality of life (short term) (subgroup nocturnal polyuria).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 5 Major adverse events (short term) (subgroup route and dose).
Figures and Tables -
Analysis 4.5

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 5 Major adverse events (short term) (subgroup route and dose).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 6 Major adverse events (short term) (subgroup nocturnal polyuria).
Figures and Tables -
Analysis 4.6

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 6 Major adverse events (short term) (subgroup nocturnal polyuria).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 7 Minor adverse events (short term).
Figures and Tables -
Analysis 4.7

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 7 Minor adverse events (short term).

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 8 Treatment withdrawal due to adverse event (short term).
Figures and Tables -
Analysis 4.8

Comparison 4 Desmopressin plus alpha‐blocker versus alpha‐blocker, Outcome 8 Treatment withdrawal due to adverse event (short term).

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 1 Number of nocturnal voids (short term).
Figures and Tables -
Analysis 5.1

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 1 Number of nocturnal voids (short term).

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 2 Major adverse events (short term).
Figures and Tables -
Analysis 5.2

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 2 Major adverse events (short term).

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 3 Minor adverse events (short term).
Figures and Tables -
Analysis 5.3

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 3 Minor adverse events (short term).

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 4 Treatment withdrawal due to adverse event (short term).
Figures and Tables -
Analysis 5.4

Comparison 5 Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic, Outcome 4 Treatment withdrawal due to adverse event (short term).

Summary of findings for the main comparison. Desmopressin versus placebo for men with nocturia (short term)

Participants: men with nocturia

Setting: likely outpatient

Intervention: desmopressin

Control: placebo

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Assumed risk with placebo

Corresponding risk difference with desmopressin

Number of nocturnal voids
assessed with: voiding diary
follow‐up: range 1 to 3 months

1982
(6 RCTs)

⊕⊕⊝⊝
Low1 2

The mean number of nocturnal voids ranged from 1.9 to 4.57.

MD 0.61 lower
(0.96 lower to 0.27 lower)

Quality of life ‐ not reported

Major adverse events
follow‐up: range 1 to 3 months

536
(2 RCTs)

⊕⊝⊝⊝
Very low1 2 3

RR 0.97
(0.10 to 9.03)

Study population

29 per 1000

1 fewer per 1000
(26 fewer to 233 more)

Duration of first sleep episode
assessed with: voiding diary
follow‐up: range 1 to 3 months

652
(4 RCTs)

⊕⊝⊝⊝
Very low1 2 3

The mean duration of first sleep episode ranged from 26.21 to 174 minutes.

MD 54.61 minutes higher
(13.97 higher to 95.25 higher)

Time to first void

383
(1 RCT)

⊕⊕⊝⊝
Low1 3

The mean time to first void was 72.9 minutes.

MD 40.8 minutes higher
(17.07 higher to 64.53 higher)

Minor adverse event
follow‐up: range 1 to 3 months

594
(3 RCTs)

⊕⊕⊝⊝
Low1 3

RR 0.87
(0.67 to 1.13)

Study population

257 per 1000

33 fewer per 1000
(33 more to 85 more)

Treatment withdrawal due to adverse event
follow‐up: range 1 to 3 months

614
(4 RCTs)

⊕⊕⊝⊝
Low1 3

RR 1.10
(0.56 to 2.15)

Study population

49 per 1000

5 more per 1000
(21 fewer to 56 more)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for study limitations: unclear or high risk of bias for one or more domains in at least 50% of the studies.
2Downgraded by one level for inconsistency: substantial heterogeneity among studies.
3Downgraded by one level for imprecision: confidence interval was wide or crossed assumed threshold of clinically important difference (or both).

Figures and Tables -
Summary of findings for the main comparison. Desmopressin versus placebo for men with nocturia (short term)
Summary of findings 2. Desmopressin versus placebo for men with nocturia (intermediate term)

Participants: men with nocturia

Setting: likely outpatient

Intervention: desmopressin

Control: placebo

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Assumed risk with placebo

Corresponding risk difference with desmopressin

Number of nocturnal voids
assessed with: voiding diary
follow‐up: range 3 to 12 months

115
(1 RCT)

⊕⊕⊝⊝
Low1,2

Mean number of nocturnal voids was 4.14 voids.

MD 0.85 voids fewer
(1.17 fewer to 0.53 fewer)

Quality of life ‐ not reported

Major adverse events
follow‐up: range 3 to 12 months

115
(1 RCT)

⊕⊕⊝⊝
Low1,2,3

RR 3.05
(0.13 to 73.39)

Study population

Duration of first sleep episode
assessed with: voiding diary
follow‐up: range 3 to 12 months

115
(1 RCT)

⊕⊕⊕⊝
Moderate1

Mean duration of first sleep episode was 101.6 minutes.

MD 18.4 minutes higher
(11.6 higher to 25.2 higher)

Time to first void ‐ not reported

Minor adverse events
follow‐up: range 3 to 12 months

115
(1 RCT)

⊕⊕⊝⊝
Low1,2

RR 0.86
(0.49 to 1.49)

Study population

328 per 1000

46 fewer per 1000
(167 fewer to 161 more)

Treatment withdrawal due to adverse event
follow‐up: range 3 to 12 months

115
(1 RCT)

⊕⊕⊝⊝
Low1,2,3

RR 3.05
(0.13 to 73.39)

Study population

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for study limitations: unclear risk of bias for one or more domains in the included study.
2Downgraded by one level for imprecision: confidence interval was wide or crossed assumed threshold of clinically important difference (or both).
3Only one event in desmopressin group.

Figures and Tables -
Summary of findings 2. Desmopressin versus placebo for men with nocturia (intermediate term)
Summary of findings 3. Desmopressin versus behaviour modifications for men with nocturia (short term)

Participants: men with nocturia

Setting: likely outpatient

Intervention: desmopressin

Control: fluid restriction during nighttime

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Assumed risk with behaviour modification

Corresponding risk difference with desmopressin

Number of nocturnal voids ‐ not reported

Quality of life ‐ not reported

Major adverse events ‐ not reported

Duration of first sleep episode
assessed with: not reported
follow‐up: mean 2 months

60
(1 RCT)

⊕⊕⊝⊝
Low1,2

Mean duration of first sleep episode was 150 minutes.

MD 90 minutes higher
(1.95 higher to 178.05 higher)

Time to first void ‐ not reported

Minor adverse events ‐ not reported

Treatment withdrawal due to adverse event ‐ not reported

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for study limitations: unclear risk of bias in almost all domains in the included study.
2Downgraded by one level for imprecision: confidence interval crossed assumed threshold of clinically important difference.

Figures and Tables -
Summary of findings 3. Desmopressin versus behaviour modifications for men with nocturia (short term)
Summary of findings 4. Desmopressin versus alpha‐blocker for men with nocturia (short term)

Participants: men with nocturia

Setting: likely outpatient

Intervention: desmopressin

Control: alpha‐blocker

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Assumed risk with alpha‐blocker

Corresponding risk difference with desmopressin

Number of nocturnal voids
assessed with: voiding diary
follow‐up: range 1 to 3 months

31
(1 RCT)

⊕⊕⊕⊝
Moderate1

Mean number of nocturnal voids was 1.2 voids.

MD 0.3 voids more
(0.2 fewer to 0.8 more)

Quality of life
assessed with: IPSS and N‐QoL
follow‐up: range 1 to 3 months

31
(1 RCT)

⊕⊕⊕⊝
Moderate1

Mean quality of life was 1.8 bothersome.

MD 0
(0.35 lower to 0.35 higher)

Major adverse events
follow‐up: range 1 to 3 months

31
(1 RCT)

⊕⊕⊝⊝
Low1,2

Not estimable

Study population

Duration of first sleep episode ‐ not reported

Time to first void ‐ not reported

Minor adverse events
follow‐up: range 1 to 3 months

31
(1 RCT)

⊕⊝⊝⊝
Very low1,3

RR 1.07
(0.07 to 15.57)

Study population

63 per 1000

4 more per 1000
(58 fewer to 911 more)

Treatment withdrawal due to adverse event
follow‐up: range 1 to 3 months

31
(1 RCT)

⊕⊕⊝⊝
Low1,2

Not estimable

Study population

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; IPSS: International Prostate Symptom Score; MD: mean difference; N‐QoL: Nocturia‐Quality of Life questionnaire; RCT: randomised controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for study limitations: unclear or high risk of bias for one or more domains in the included study.
2Downgraded by one level for imprecision: no event in either group.
3Downgraded by two levels for imprecision: confidence interval was wide and crossed assumed threshold of clinically important difference.

Figures and Tables -
Summary of findings 4. Desmopressin versus alpha‐blocker for men with nocturia (short term)
Summary of findings 5. Desmopressin plus alpha‐blocker versus alpha‐blocker for men with nocturia (short term)

Participants: men with nocturia

Setting: likely outpatient

Intervention: desmopressin + alpha‐blocker

Control: alpha‐blocker alone

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Assumed risk with alpha‐blocker

Corresponding risk difference with desmopressin + alpha‐blocker

Number of nocturnal voids

assessed with: voiding diary
follow‐up: range 1 to 3 months

341
(3 RCTs)

⊕⊕⊕⊝
Moderate1

Mean number of nocturnal voids ranged from 1.68 to 2.6.

MD 0.47 voids fewer
(0.73 fewer to 0.21 fewer)

Quality of life

assessed with: IPSS and N‐QoL
follow‐up: range 1 to 3 months

341
(3 RCTs)

⊕⊕⊕⊝
Moderate1

Mean quality of life ranged from 1.53 to 4.4.

MD 0.29 lower
(0.51 lower to 0.07 lower)

Major adverse events
follow‐up: range 1 to 3 months

402
(3 RCTs)

⊕⊕⊝⊝
Low1,2

RR 0.30
(0.01 to 7.32)

Study population

5 per 1000

3 fewer per 1000
(5 fewer to 32 more)

Duration of first sleep episode ‐ not reported

Time to first void ‐ not reported

Minor adverse events
follow‐up: range 1 to 3 months

402
(3 RCTs)

⊕⊝⊝⊝
Very low1,3

RR 1.60
(0.15 to 16.82)

Study population

80 per 1000

48 more per 1000
(68 fewer to 1000 more)

Treatment withdrawal due to adverse event
follow‐up: range 1 to 3 months

402
(3 RCTs)

⊕⊕⊝⊝
Low1,2

RR 2.84
(0.46 to 17.66)

Study population

5 per 1000

9 more per 1000
(3 fewer to 83 more)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; IPSS: International Prostate Symptom Score; MD: mean difference; N‐QoL: Nocturia‐Quality of Life questionnaire; RCT: randomised controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for study limitations: unclear or high risk of bias for one or more domains among the included studies.
2Downgraded by one level for imprecision: no event or very rare event resulting in wide confidence interval.
3Downgraded by two level for imprecision: confidence interval was wide and crossed assumed threshold of clinically important difference.

Figures and Tables -
Summary of findings 5. Desmopressin plus alpha‐blocker versus alpha‐blocker for men with nocturia (short term)
Summary of findings 6. Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic for men with nocturia (short term)

Participants: men with nocturia

Setting: likely outpatient

Intervention: desmopressin + alpha‐blocker

Control: anticholinergic + alpha‐blocker

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Assumed risk with alpha‐blocker + anticholinergic

Corresponding risk difference with desmopressin + alpha‐blocker

Number of nocturnal voids
assessed with: voiding diary
follow‐up: range 1 to 3 months

405
(1 RCT)

⊕⊕⊕⊝
Moderate1

Mean number of nocturnal voids was 6.97 voids.

MD 0.43 voids fewer
(0.97 fewer to 0.11 more)

Quality of life ‐ not reported

Major adverse events
follow‐up: range 1 to 3 months

427
(1 RCT)

⊕⊕⊝⊝
Low1,2

Not estimable

Study population

Duration of first sleep episode ‐ not reported

Time to first void ‐ not reported

Minor adverse events
follow‐up: range 1 to 3 months

427
(1 RCT)

⊕⊕⊝⊝
Low1,3

RR 0.22
(0.05 to 0.98)

Study population

45 per 1000

35 fewer per 1000
(43 fewer to 1 fewer)

Treatment withdrawal due to adverse event
follow‐up: range 1 to 3 months

427
(1 RCT)

⊕⊕⊝⊝
Low1,3

RR 0.22
(0.05 to 0.98)

Study population

45 per 1000

35 fewer per 1000
(43 fewer to 1 fewer)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

1Downgraded by one level for study limitations: unclear risk of bias for one or more domains in the included study.
2Downgraded by one level for imprecision: no event in either group.
3Downgraded by one level for imprecision: confidence interval crossed assumed threshold of clinically important difference.

Figures and Tables -
Summary of findings 6. Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic for men with nocturia (short term)
Table 1. Baseline characteristics

Study

Setting

Trial period

Description of participants

Intervention(s) and comparator(s)

Duration of intervention
(duration of follow‐up)

Ahmed 2015a

Outpatient/Egypt

2011 to 2014

People with LUTS/BPH aged ≥ 50 years with nocturia (≥ 2 voids/night), nocturnal polyuria (nocturnal urine volume > 30% of 24‐hour urine volume)

I: desmopressin 60 μg ODT + tamsulosin

3 months

C: tamsulosin

Cannon 1999

UK

NR

Men aged > 50 years with nocturnal polyuria (using 48‐hour inpatient monitoring or 1‐week frequency volume chart)

I: desmopressin nasal spray 20 μg

4 weeks

C: placebo

Ceylan 2013

Outpatient/Turkey

2011

Men with advanced age, complaints of LUTS and nocturia (≥ 3 times/night)

I: desmopressin nasal spray 20 μg

2 months

C: doxazosin

Kim 2017

Multicentre/South Korea

NR

Men aged 40 to 65 years with LUTS (IPSS > 13), nocturia (≥ 2 episodes/night), and nocturnal polyuria (NPI > 33%)

I: desmopressin 0.2 mg oral + alpha‐blocker

8 weeks

C: placebo + alpha‐blocker

Koca 2012

Outpatient/Turkey

NR

Men aged 50 to 70 years with LUTS and nocturia (≥ 2/night)

I: desmopressin 0.2 mg oral with alfuzosin

3 months

C: alfuzosin

Mattiasson 2002

Multicentre/Denmark,
Sweden, Netherlands, the UK, and the USA

NR

Men aged ≥ 18 years with nocturia (2 voids/night, nocturia index scores > 1)

I: desmopressin 0.1 mg/0.2 mg/0.4 mg oral; dose titration

3 weeks

C: placebo

Rezakhaniha 2011

Outpatient/single centre/Iran

2008 to 2009

Older men (mean age about 63 to 64 years) with voiding ≥ 2/night

I: desmopressin 0.1 mg oral

8 weeks

C: placebo

Serenity Pharmaceuticals2016

Multicentre/USA and Canada

NR

Men or women aged ≥ 50 years with nocturia (≥ 2 nocturic episodes/night)

I: desmopressin nasal spray 0.75 μg, 1.0 μg, or 1.5 μg

12 weeks

C: placebo

Shin 2014a

South Korea

2010 to 2013

Men aged ≥ 50 years with LUTS due to bladder outlet obstruction (Qmax ≤ 15 mL/second, IPSS ≥ 14) and nocturia (≥ 1 void/night)

I: desmopressin 0.2 mg oral + tamsulosin

4 weeks

C: solifenacin + tamsulosin

Wang 2011a

Single centre/Taiwan

2007 to 2009

Men aged ≥ 65 years with BPH (IPSS > 13), nocturia (≥ 2 voids/night), and nocturnal polyuria (nocturnal urine volume > 30%)

I: desmopressin 0.1 mg oral

12 months

C: placebo

Wang 2012

Outpatient/single centre/China

2009 to 2010

Older men (age not reported)

I: desmopressin 0.1 mg oral

8 weeks

C: placebo

Weiss 2012a

Multicentre/Canada and the USA

2007 to 2008

Men and women aged ≥ 18 years with nocturia (≥ 2 voids/night)

I: desmopressin 10 µg, 25 µg, 50 µg, or 100 µg ODT

4 weeks

C: placebo

Weiss 2013

Multicentre/Canada and the USA

2010 to 2013

Men aged ≥ 18 years with nocturia (≥ 2 voids/night)

I: desmopressin 50 μg, 75 µg ODT

3 months

C: placebo

Yamaguchi 2013

Multicentre/Japan

2010 to 2011

Men and women aged 55 to 75 years with nocturia (≥ 2 voids/night)

I: desmopressin 10 µg, 25 µg, 50 µg, or 100 µg ODT

4 weeks

C: placebo

BPH: benign prostatic hyperplasia; C: comparator; I: intervention; IPSS: International Prostate Symptom Score; LUTS: lower urinary tract symptoms; NPI: nocturnal polyuria index; NR: not reported; ODT: orally disintegrating tablet; Qmax: maximum flow rate.

Figures and Tables -
Table 1. Baseline characteristics
Table 2. Participant disposition

Intervention(s) and comparator(s)

Sample size

Screened/eligible
(n)

Randomised
(n)

ITT
(n)

Analysed
(n: total/male)

Finishing trial
(n)

Randomised finishing trial
(%)

Follow‐up
(extended follow‐up)1

Ahmed 2015a

I: desmopressin + tamsulosin

100

397/273

139

123

123

107

77.0

3 months

C: tamsulosin

100

134

125

125

103

76.9

Total:

273

248

248

210

76.9

Cannon 1999

I: desmopressin

‐/‐

8 weeks (cross‐over study design)

C: placebo

Total:

20

18

18

90.0

Ceylan 2013

I: desmopressin

84/31

15

15

15

15

100.0

2 months

C: doxazosin

16

16

16

16

100.0

Total:

31

31

31

31

100.0

Kim 2017

I: desmopressin + alpha‐blocker

121/109

57

57

47

47

82.4

8 weeks

C: placebo + alpha‐blocker

52

52

39

39

75.0

Total:

109

109

86

86

78.9

Koca 2012

I: desmopressin + alfuzosin

‐/49

22

22

3 months

C: alfuzosin

23

23

Total:

49

45

45

91.8

Mattiasson 2002

I: desmopressin

55

341/224

86

86

86

81

94.2

3 weeks

C: placebo

55

65

65

65

62

95.4

Total:

151

151

151

143

94.7

Rezakhaniha 2011

I: desmopressin

93/60

30

30

30

30

100.0

8 weeks

C: placebo

30

30

30

30

100.0

Total:

60

60

60

60

100.0

Serenity Pharmaceuticals 20162

I1: desmopressin 0.75 μg

3565/1707

458

448

448/252

401

87.5

12 weeks

I2: desmopressin 1.0 μg

188

183

183/109

163

86.7

I3: desmopressin 1.5 μg

452

439

439/251

387

85.6

C: placebo

458

446

446/258

408

89.0

Total:

1556

1516

1516/870

1359

87.3

Shin 2014a

I: desmopressin + tamsulosin

435/427

205

205

205

196

95.6

8 weeks (cross‐over study design)

C: tamsulosin + solifenacin

222

222

222

209

94.1

Total:

427

427

427

405

94.8

Wang 2011a

I: desmopressin

45

‐/136

NR

57

57

12 months

C: placebo

45

NR

58

58

Total:

126

115

115

91.3

Wang 2012

I: desmopressin

‐/60

30

30

30

30

100.0

8 weeks

C: placebo

30

30

30

30

100.0

Total:

60

60

60

60

100.0

Weiss 2012a2

I1: desmopressin 10 µg

1412/799

163

155

155/82

144

88.3

4 weeks

I2: desmopressin 25 µg

158

152

152/87

148

93.7

I3: desmopressin 50 µg

158

148

148/77

138

87.3

I4: desmopressin 100 µg

160

146

146/80

135

84.4

C: placebo

160

156

156/90

145

90.6

Total:

799

757

757/416

710

88.9

Weiss 2013

I1: desmopressin 50 µg

130

1013/395

119

119

100

3 months

I2: desmopressin 75 µg

130

124

124

103

C: placebo

130

142

142

120

Total:

395

385

385

323

81.8

Yamaguchi 20132

I1: desmopressin 10 µg

177/139

28

28

23/11

23

82.1

3 months

I2: desmopressin 25 µg

25

25

22/11

22

88.0

I3: desmopressin 50 µg

29

29

21/10

21

72.4

I4: desmopressin 100 µg

30

30

23/11

23

76.6

C: placebo

27

27

23/11

23

85.1

Total:

139

139

112/54

112

80.5

Overall total

Men

2966

Women

1045

Total:

4195

4011

‐ denotes not reported; C: comparator; I: intervention; ITT: intention‐to‐treat; n: number of participants.

1Follow‐up under randomised conditions until end of trial or if not available, duration of intervention; extended follow‐up refers to follow‐up of participants once the original study was terminated as specified in the power calculation.
2Study included men and women.

Figures and Tables -
Table 2. Participant disposition
Comparison 1. Desmopressin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of nocturnal voids (short term) (subgroup route) Show forest plot

6

1982

Mean Difference (IV, Random, 95% CI)

‐0.61 [‐0.96, ‐0.27]

1.1 Intranasal

1

870

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.34, ‐0.06]

1.2 Sublingual

3

851

Mean Difference (IV, Random, 95% CI)

‐0.37 [‐0.71, ‐0.03]

1.3 Oral

2

261

Mean Difference (IV, Random, 95% CI)

‐1.14 [‐1.41, ‐0.86]

2 Number of nocturnal voids (intermediate term) Show forest plot

1

115

Mean Difference (IV, Random, 95% CI)

‐0.85 [‐1.17, ‐0.53]

3 Major adverse events (short term) (subgroup route and dose) Show forest plot

2

536

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.10, 9.03]

3.1 Sublingual/low dose

1

385

Risk Ratio (M‐H, Random, 95% CI)

2.53 [0.73, 8.73]

3.2 Oral/high dose

1

151

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.03, 2.37]

4 Major adverse events (intermediate term) Show forest plot

1

115

Risk Ratio (M‐H, Random, 95% CI)

3.05 [0.13, 73.39]

5 Duration of first sleep episode (short term) Show forest plot

4

652

Mean Difference (IV, Random, 95% CI)

54.61 [13.97, 95.25]

6 Duration of first sleep episode (intermediate term) Show forest plot

1

115

Mean Difference (IV, Random, 95% CI)

18.40 [11.60, 25.20]

7 Time to first void (short term) [minutes] Show forest plot

1

383

Mean Difference (IV, Random, 95% CI)

40.8 [17.07, 64.53]

8 Minor adverse events (short term) Show forest plot

3

594

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.67, 1.13]

9 Minor adverse events (intermediate term) Show forest plot

1

115

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.49, 1.49]

10 Treatment withdrawal due to adverse event (short term) Show forest plot

4

614

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.56, 2.15]

11 Treatment withdrawal due to adverse event (intermediate term) Show forest plot

1

115

Risk Ratio (M‐H, Random, 95% CI)

3.05 [0.13, 73.39]

12 Number of nocturnal voids (short term) (subgroup dose) Show forest plot

6

1982

Mean Difference (IV, Random, 95% CI)

‐0.65 [‐0.98, ‐0.33]

12.1 Very low dose (≤ 1.5 μg)

1

870

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.34, ‐0.06]

12.2 Low dose (< 100 μg)

3

711

Mean Difference (IV, Random, 95% CI)

‐0.33 [‐0.72, 0.06]

12.3 High dose (≥ 100 μg)

4

401

Mean Difference (IV, Random, 95% CI)

‐1.03 [‐1.41, ‐0.66]

13 Number of nocturnal voids (short term) (subgroup nocturnal polyuria) Show forest plot

6

1982

Mean Difference (IV, Random, 95% CI)

‐0.61 [‐0.96, ‐0.27]

13.1 Men with nocturia

5

1867

Mean Difference (IV, Random, 95% CI)

‐0.45 [‐0.73, ‐0.17]

13.2 Men with nocturia and nocturnal polyuria

1

115

Mean Difference (IV, Random, 95% CI)

‐1.28 [‐1.64, ‐0.92]

14 Number of nocturnal voids (short term) (sensitivity run‐in period) Show forest plot

4

966

Mean Difference (IV, Random, 95% CI)

‐0.66 [‐1.17, ‐0.14]

15 Major adverse events (short term) (sensitivity run‐in period) Show forest plot

1

385

Risk Ratio (M‐H, Random, 95% CI)

2.53 [0.73, 8.73]

16 Number of nocturnal voids (short term) (sensitivity clinical dosage) Show forest plot

6

1586

Mean Difference (IV, Random, 95% CI)

‐0.76 [‐1.15, ‐0.38]

17 Major adverse events (short term) (sensitivity clinical dosage) Show forest plot

2

417

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.10, 9.71]

17.1 Sublingual/low dose

1

266

Risk Ratio (M‐H, Random, 95% CI)

2.67 [0.71, 10.11]

17.2 Oral/high dose

1

151

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.03, 2.37]

Figures and Tables -
Comparison 1. Desmopressin versus placebo
Comparison 2. Desmopressin versus behaviour modification

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Duration of first sleep episode (short term) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

90.0 [1.95, 178.05]

Figures and Tables -
Comparison 2. Desmopressin versus behaviour modification
Comparison 3. Desmopressin versus alpha‐blocker

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of nocturnal voids (short term) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

0.30 [‐0.20, 0.80]

2 Quality of life (short term) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.35, 0.35]

3 Major adverse events (short term) Show forest plot

1

31

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Minor adverse events (short term) Show forest plot

1

31

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.07, 15.57]

5 Treatment withdrawal due to adverse event (short term) Show forest plot

1

31

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 3. Desmopressin versus alpha‐blocker
Comparison 4. Desmopressin plus alpha‐blocker versus alpha‐blocker

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of nocturnal voids (short term) (subgroup route and dose) Show forest plot

3

341

Mean Difference (IV, Random, 95% CI)

‐0.47 [‐0.73, ‐0.21]

1.1 Sublingual/low dose

1

210

Mean Difference (IV, Random, 95% CI)

‐0.66 [‐0.90, ‐0.42]

1.2 Oral/high dose

2

131

Mean Difference (IV, Random, 95% CI)

‐0.31 [‐0.60, ‐0.02]

2 Number of nocturnal voids (short term) (subgroup nocturnal polyuria) Show forest plot

3

341

Mean Difference (IV, Random, 95% CI)

‐0.47 [‐0.73, ‐0.21]

2.1 Men with nocturia

1

45

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.74, 0.14]

2.2 Men with nocturia and nocturnal polyuria

2

296

Mean Difference (IV, Random, 95% CI)

‐0.52 [‐0.86, ‐0.18]

3 Quality of life (short term) (subgroup route and dose) Show forest plot

3

341

Mean Difference (IV, Random, 95% CI)

‐0.29 [‐0.51, ‐0.07]

3.1 Sublingual/low dose

1

210

Mean Difference (IV, Random, 95% CI)

‐0.23 [‐0.49, 0.03]

3.2 Oral/high dose

2

131

Mean Difference (IV, Random, 95% CI)

‐0.44 [‐0.85, ‐0.03]

4 Quality of life (short term) (subgroup nocturnal polyuria) Show forest plot

3

341

Mean Difference (IV, Random, 95% CI)

‐0.29 [‐0.51, ‐0.07]

4.1 Men with nocturia

1

45

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.84, 0.44]

4.2 Men with nocturia and nocturnal polyuria

2

296

Mean Difference (IV, Random, 95% CI)

‐0.34 [‐0.67, ‐0.01]

5 Major adverse events (short term) (subgroup route and dose) Show forest plot

3

402

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.01, 7.32]

5.1 Sublingual/low dose

1

248

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Oral/high dose

2

154

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.01, 7.32]

6 Major adverse events (short term) (subgroup nocturnal polyuria) Show forest plot

3

402

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.01, 7.32]

6.1 Men with nocturia

1

45

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Men with nocturia and nocturnal polyuria

2

357

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.01, 7.32]

7 Minor adverse events (short term) Show forest plot

3

402

Risk Ratio (M‐H, Random, 95% CI)

1.60 [0.15, 16.82]

8 Treatment withdrawal due to adverse event (short term) Show forest plot

3

402

Risk Ratio (M‐H, Random, 95% CI)

2.84 [0.46, 17.66]

Figures and Tables -
Comparison 4. Desmopressin plus alpha‐blocker versus alpha‐blocker
Comparison 5. Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of nocturnal voids (short term) Show forest plot

1

405

Mean Difference (IV, Random, 95% CI)

‐0.43 [‐0.97, 0.11]

2 Major adverse events (short term) Show forest plot

1

427

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Minor adverse events (short term) Show forest plot

1

427

Risk Ratio (M‐H, Random, 95% CI)

0.22 [0.05, 0.98]

4 Treatment withdrawal due to adverse event (short term) Show forest plot

1

427

Risk Ratio (M‐H, Random, 95% CI)

0.22 [0.05, 0.98]

Figures and Tables -
Comparison 5. Desmopressin plus alpha‐blocker versus alpha‐blocker plus anticholinergic