Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics)

Cathryn MA Glazener; Jonathan HC Evans; Rachel E Peto

doi:10.1002/14651858.CD002238

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Analysis 1.1

Comparison 1 DRUGS vs PLACEBO, Outcome 1 Number of wet nights per week.

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Study	Drug	Placebo
amphetamine sulphate/ephedrine + atropine vs placebo
Wright 1974	Mean = 4.1, N=8	Mean = 3.5, N=10
furosemide vs placebo
Moltke 1979	Mean = 5.11, N=41	Mean = 4.69, N=44
meprobamate vs placebo
Breger 1961	Mean = 3.26, N=34	Mean = 3.21, N=33
propantheline bromide vs placebo
Leys 1956	Mean = 4.7, N=33	mean = 5.36, N=32
emepronium vs placebo
Petersen 1974#	Mean = 4.36, N=61	Mean = 4.37, N=61
indoramin 20 mg vs placebo
Shaffer 1978#	Mean = 5.2, N=14	Mean = 5.35, N=14
indoramin 10 mg vs placebo
Shaffer 1978#	Mean = 4.99, N=14	Mean = 5.35, N=14
propantheline vs placebo
Mayon‐White 1956	Mean = 2.11, n=9	Mean = 1.75, n=6

Analysis 1.2

Comparison 1 DRUGS vs PLACEBO, Outcome 2 Number of wet nights per week (no SDs).

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Analysis 1.3

Comparison 1 DRUGS vs PLACEBO, Outcome 3 Number not achieving 14 consecutive dry nights.

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Analysis 1.4

Comparison 1 DRUGS vs PLACEBO, Outcome 4 Number failing or relapsing after end of treatment.

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Study	Drug	Placebo
propantheline bromide vs placebo
Leys 1956	Mean = 4.96, N=33	Mean = 5.33, N=32

Analysis 1.5

Comparison 1 DRUGS vs PLACEBO, Outcome 5 Number of wet nights per week after treatment stopped (no SDs).

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Analysis 2.1

Comparison 2 DRUG ‐ DRUG COMPARISONS, Outcome 1 Number of wet nights per week.

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Study	Drug 1	Drug 2
furosemide vs imipramine
Moltke 1979	Mean = 5.11, N=41	Mean = 3.43, N=43
triclofos vs ephedrine
GP Research Gp 1970#	Mean = 4.1, N=28	Mean = 4.5, N=27
emepronium vs imipramine
Petersen 1974#	Mean = 4.36, N=61	Mean = 2.4, N=61
emepronium vs imipramine‐N‐oxide
Petersen 1974#	Mean = 4.36, N=61	Mean = 3.24, N=61
indoramin 20 mg vs indoramin 10 mg
Shaffer 1978#	Mean = 5.2, N=14	Mean = 4.99, N=14

Analysis 2.2

Comparison 2 DRUG ‐ DRUG COMPARISONS, Outcome 2 Number of wet nights per week (no SDs).

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Analysis 2.3

Comparison 2 DRUG ‐ DRUG COMPARISONS, Outcome 3 Number not achieving 14 consecutive dry nights.

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Analysis 2.4

Comparison 2 DRUG ‐ DRUG COMPARISONS, Outcome 4 Number failing or relapsing after treatment stopped.

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Study	Drug	Behavioural method
amphetamine sulphate/ephedrine + atropine vs alarm
Wright 1974	Mean = 4.1, N=8	Mean = 1.7, N=10

Analysis 3.2

Comparison 3 DRUG vs BEHAVIOURAL INTERVENTIONS, Outcome 2 Number of wet nights per week (no SDs).

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Analysis 3.3

Comparison 3 DRUG vs BEHAVIOURAL INTERVENTIONS, Outcome 3 Number not achieving 14 consecutive dry nights.

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Comparison 1. DRUGS vs PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of wet nights per week Show forest plot	5		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 phenmetrazine vs placebo	1	20	Mean Difference (IV, Fixed, 95% CI)	1.00 [‐2.52, 0.52]
1.2 indomethacin suppository vs placebo	2	92	Mean Difference (IV, Fixed, 95% CI)	‐3.06 [‐3.89, ‐2.23]
1.3 diclofenac sodium vs placebo	1	40	Mean Difference (IV, Fixed, 95% CI)	‐4.21 [‐5.76, ‐2.66]
1.4 diazepam vs placebo	1	50	Mean Difference (IV, Fixed, 95% CI)	‐4.87 [‐6.25, ‐3.49]
2 Number of wet nights per week (no SDs) Show forest plot			Other data	No numeric data

2.1 amphetamine sulphate/ephedrine + atropine vs placebo			Other data	No numeric data
2.2 furosemide vs placebo			Other data	No numeric data
2.3 meprobamate vs placebo			Other data	No numeric data
2.4 propantheline bromide vs placebo			Other data	No numeric data
2.5 emepronium vs placebo			Other data	No numeric data
2.6 indoramin 20 mg vs placebo			Other data	No numeric data
2.7 indoramin 10 mg vs placebo			Other data	No numeric data
2.8 propantheline vs placebo			Other data	No numeric data
3 Number not achieving 14 consecutive dry nights Show forest plot	15		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 chlorprotixine vs placebo	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.85, 1.07]
3.2 indomethacin suppository vs placebo	1	38	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.16, 0.79]
3.3 diclofenac vs placebo	2	92	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.38, 0.70]
3.4 meprobamate vs placebo	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.92, 1.35]
3.5 hydroxyzine chloride vs placebo	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.70, 0.97]
3.6 methylphenidate hydrochloride vs placebo	1	83	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.67, 0.94]
3.7 atropine sulphate + ephedrine sulphate vs placebo	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.71, 1.41]
3.8 chlordiazepoxide + amitriptyline vs placebo	1	215	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.95, 1.01]
3.9 piracetam vs placebo	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	1.38 [0.91, 2.11]
3.10 propantheline vs placebo	2	226	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.89, 1.08]
3.11 oxybutinin vs placebo	1	39	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.52, 1.24]
3.12 diazepam vs placebo	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.11, 0.46]
3.13 propantheline vs placebo	1	15	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.15, 11.64]
3.14 atomoxetine vs placebo	1	83	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.70, 0.95]
4 Number failing or relapsing after end of treatment Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 atropine sulphate + ephedrine sulphate vs placebo	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.80, 1.06]
4.2 chlordiazepoxide + amitriptyline vs placebo	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.97, 1.03]
4.3 oxybutinin vs placebo	1	23	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.79, 1.62]
5 Number of wet nights per week after treatment stopped (no SDs) Show forest plot			Other data	No numeric data

5.1 propantheline bromide vs placebo			Other data	No numeric data

Comparison 1. DRUGS vs PLACEBO

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Comparison 2. DRUG ‐ DRUG COMPARISONS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of wet nights per week Show forest plot	5		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 meprobamate + hydroxyzine vs imipramine	1	25	Mean Difference (IV, Fixed, 95% CI)	4.6 [3.24, 5.96]
1.2 ephedrine sulphate vs imipramine	1	36	Mean Difference (IV, Fixed, 95% CI)	2.05 [1.02, 3.08]
1.3 indomethacin suppository vs desmopressin (nasal drops)	1	60	Mean Difference (IV, Fixed, 95% CI)	1.45 [0.53, 2.37]
1.4 oxybutinin vs pseudoephedrine	1	20	Mean Difference (IV, Fixed, 95% CI)	0.75 [‐0.95, 2.45]
1.5 oxybutinin vs indomethacin	1	18	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐2.02, 1.62]
1.6 oxybutinin vs dicyclomine	1	58	Mean Difference (IV, Fixed, 95% CI)	‐5.70 [‐6.34, ‐5.06]
1.7 pseudoephedrine vs indomethacin	1	20	Mean Difference (IV, Fixed, 95% CI)	‐0.95 [‐2.67, 0.77]
2 Number of wet nights per week (no SDs) Show forest plot			Other data	No numeric data

2.1 furosemide vs imipramine			Other data	No numeric data
2.2 triclofos vs ephedrine			Other data	No numeric data
2.3 emepronium vs imipramine			Other data	No numeric data
2.4 emepronium vs imipramine‐N‐oxide			Other data	No numeric data
2.5 indoramin 20 mg vs indoramin 10 mg			Other data	No numeric data
3 Number not achieving 14 consecutive dry nights Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 meprobamate + hydroxyzine vs imipramine	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.04, 2.69]
3.2 hydroxyzine chloride vs methylphenidate hydrochloride	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.84, 1.30]
3.3 triclofos vs ephedrine	1	56	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.80, 1.07]
3.4 diclofenac vs desmopressin (nose drops)	1	62	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [1.13, 3.33]
3.5 oxybutinin vs imipramine	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.65, 2.39]
3.6 oxybutinin vs imipramine + oxybutinin	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	1.88 [0.95, 3.71]
3.7 propantheline vs propantheline + phenobarbitone	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.96, 1.24]
4 Number failing or relapsing after treatment stopped Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 meprobamate + hydroxyzine vs imipramine	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.90, 1.59]
4.2 oxybutinin vs imipramine	1	21	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.76, 1.50]
4.3 oxybutinin vs imipramine + oxybutinin	1	31	Risk Ratio (M‐H, Fixed, 95% CI)	1.96 [1.17, 3.27]

Comparison 2. DRUG ‐ DRUG COMPARISONS

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Comparison 3. DRUG vs BEHAVIOURAL INTERVENTIONS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Number of wet nights per week	0		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2 Number of wet nights per week (no SDs) Show forest plot			Other data	No numeric data

2.1 amphetamine sulphate/ephedrine + atropine vs alarm			Other data	No numeric data
3 Number not achieving 14 consecutive dry nights Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 amphetamine vs alarm	1	33	Risk Ratio (M‐H, Fixed, 95% CI)	2.20 [1.12, 4.29]
3.2 methedrine + alarm vs alarm	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.20]
3.3 piracetam vs play + supportive therapy	1	33	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.01, 2.75]
3.4 piracetam vs piracetam + play + supportive therapy	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	2.67 [1.18, 6.03]

Comparison 3. DRUG vs BEHAVIOURAL INTERVENTIONS

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