Methods

RCT (double‐blind crossover trial)
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Teaching hospital, Baghdad

Participants

No. of children (boys): 20 (6)
Incl: primary enuresis, every night
Excl: asthma, renal and gastrointestinal disorders, hypersensitivity to NSAIDs
Age: 6‐17 years (mean 10)

Interventions

A (20): diclofenac sodium 50 mg orally
B (20): placebo

Duration of treatment: 30 days each arm
Follow up: none
Non‐responders treated with 75 mg diclofenac for 30 more days

Outcomes

Mean DRY nights (SEM): A: 21.7 (1.4), B: 3.65 (3.1)
= mean (SD) wet nights per week: A: 1.94 (1.47), B: 6.15 (3.22)
No. with at least 14 wet nights in 30: A: 5/20, B: 18/20
Adverse events: none

Notes

Diclofenac sodium is a prostaglandin synthesis inhibitor
No washout
Groups comparable at baseline (as crossover trial)

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (double‐blind crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Outpatient clinic, teaching hospital, Baghdad

Participants

No. of children (boys): 19 (7)
Incl: primary nocturnal enuresis, failed previous treatment
Excl: asthma, renal and gastrointestinal disorders, hypersensitivity to drugs
Previous treatment: antispasmodics, fluid restriction, imipramine, all stopped 2 months before trial
Age: mean 9 years (range 6‐15)
Baseline wetting: every night

Interventions

A (19): indomethacin suppository 50 mg
B (19): placebo
Duration of treatment: 30 days
Follow up: if not cured, continued with 100 mg indomethacin unblinded

Outcomes

Mean DRY nights during trial (SD): A: 19.5 (10.5), B: 3.6 (5.7)
= mean wet nights per week: A: 2.45 (2.45), B: 6.16 (1.33)
No. not achieving 10 dry nights: A: 5/19, B: 14/19
Adverse events: A: mild rectal burning sensation

Notes

Groups comparable at baseline as crossover
No washout

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned

Participants

No. of children (boys): 78 (48)
Incl: primary nocturnal enuresis; at least 3 wet nights /week
Excl: organic causes
Previous Rx: none
Age: 6‐18 y

Interventions

A (16): imipramine 1mg/kg/day
B (20): diclofenac sodium
C (30): imipramine + diclofenac
D (12): placebo
Duration of treatment: 4 weeks
Follow up: 1 and 3 months

Outcomes

No. improving >50%: A: 2/16, B: 4/20, C: 2/30, D: 6/12
No. relapsing: A: 6, B: 0, C: 4, D: 0

Adverse events: 8 had mild gastrointestinal symptoms, but not clear which groups

Notes

No useable data
Unexplained difference in size of groups at allocation

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (divided by random selection)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: children's psychiatric service, Johns Hopkins Hospital, Baltimore, referred by doctor or school

Participants

No. of children: 100
Dropouts: 33
Excl: organic uropathy, severe learning difficulties
Age: 5‐14 years
Baseline wetting: A: 6.7 wet nights per week, B: 6.54

Interventions

A (34): meprobamate (3x/ day; dosage depends on age: 5‐9 years = 200 mg; 10‐14 = 400 mg)
B (33): identical placebo

Duration of treatment: 3 months
Follow up: none

Outcomes

Mean wet nights during trial: A: 3.26, B: 3.21
No. not achieving 14 dry nights during trial: A: 31/34, B: 27/33
Outcomes not different according to sex

Notes

No SDs
No reprimands, no fluid restriction, no lifting
Dropouts 'comparable from each group'

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (divided by random selection)
Systematic baseline measure of wetting: Yes (but not fully reported)
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: children's psychiatric service, Johns Hopkins Hospital, Baltimore, referred by doctor or school

Participants

No. of children: 150
Dropouts: 26
Excl: organic uropathy, severe learning difficulty
Age: 5‐14 years
Baseline wetting: 92/124 wet 7x/week; 32/124 wet less often

Interventions

A (41): hydroxyzine chloride age 5‐9, 10 mg 2x/day; age 10‐14 10‐20 mg 3x/day
B (44): methylphenidate hydrochloride (Ritalin) age 5‐9 years 5 mg 2x/day; age 10‐14 5‐10 mg 3x/day
C (39): placebo

Duration of treatment: 3 months (minimum 2)
Follow up: None

Outcomes

No. not achieving 14 dry nights during trial: A: 33/41, B: 34/44, C: 38/39

Notes

Hydroxyzine is a tranquillizer, methylphenidate is a stimulant
No reprimands, no fluid restriction, no waking

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (double blind study)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Paediatric Department, New York

Participants

No. of children (boys): 50 (28)
Incl: enuresis
Age: 4‐15 years
Baseline wetting: A: 4.64 wet nights, B: 5.4

Interventions

A (25): atropine sulphate 0.15 mg + ephedrine sulphate 7.5 mg: age <10 years = 2 tablets, > 10 = 4 tablets
B (25): matching placebo

Duration of treatment: 1 month
Follow up: 2 months, then all children received active treatment

Outcomes

No. not achieving 14 dry nights: A: 18/25, B: 18/25
Excellent or moderate improvement: A: 11/25, B: 17/25
Relapse or fail after trial: A: 23/25, B: 25/25
Adverse events: A: 6/25 (dry mouth, insomnia, blurred vision, dizziness, constipation, nervousness, flushing)
B: 0/25
Side effects attributed to dose being too high

Notes

Groups comparable on baseline wetting
All children also had extra fluids and bladder training during the day, fluid restriction at night, wakening, reward for dry nights

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT
Systematic baseline measure of wetting: No
Organic causes excluded: No
Daytime wetting excluded: Not mentioned
Setting: Children recruited from community survey

Participants

No. of children 118 (33 properly included in trial)
Dropouts: 25 cured before trial, 32 improved, 9 not suitable, 15 defaulted, 4 received wrong intervention
Incl: aged 8‐14, wet at least once per week, suitable family circumstances
Ages: 8‐14 years

Interventions

A (16): Alarm (+ amphetamine for some children if not wakened by bell)
B (17): Amphetamine 2.5 to 5mg, increasing weekly if no response, decreasing if response, stopped if sleepless or restless
Duration of treatment: up to 6 months

Outcomes

No. not achieving 21 dry nights: A: 6/16, B: 14/17
Failure to comply with treatment properly: A: 4/17, B: 6/16

Notes

Successful treatment requires the families to understand the commitment involved
Results including failure to comply in group as allocated

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (double blind placebo controlled, stratified by sex)
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Belfast Hospital for Sick Children

Participants

No. of children (boys): 241 (140)
Dropouts before start of study: A: 10, B: 16
Dropouts before end of FU: A: 6, B: 9
Incl: nocturnal enuresis at least 6x/week in previous year
Ages: 5‐14 years

Interventions

A (121): chlordiazepoxide (5 mg) + amitriptyline (12.5 mg)
B (120): Placebo

Duration of treatment: 8 weeks
Follow up: 8 weeks

Outcomes

No. not achieving 14 dry nights: A: 109/111, B: 104/104
No. improving by 50%: A: 50/111, B: 88/104
No. not achieving 14 dry nights or relapsing after: A: 103/104, B: 95/96
Improved (at least 50% dry nights): A: 69/104, B: 82/96

Notes

Chlordiazepoxide used to suppress emotional stimuli
Groups and dropouts comparable

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned

Participants

Number of children (boys): 69 (37)
Dropouts: 24
Incl: age 4+; no organic causes;
Previous treatment: none
Age: 70% between 4 and 7
Baseline wetting: wet bed at least 4 x/week for those under 7 and 2x/week for those over 7

Interventions

A (45): Chlorprotixine (Truxal) 5mg
B (45): placebo

Duration of treatment: 6 weeks each arm of trial
Follow up: none

Outcomes

Number of children achieving 100% dry nights:
A: 4/45, B: 2/45
Side effects: drowsiness

Notes

Danish language (translated)
Results not clear

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (double‐blind crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: community patients in 16 GP practices

Participants

No. of children (boys): 55 (33)
Incl: at least 3 wet nights per week
Excl: renal abnormalities
Age: 5‐15 years
Baseline wetting: 5.6 wet nights per week (A: 5.3, B: 5.6)

Interventions

A (28): triclofos 0.5 gm
B (27): ephedrine 15 mg
Dose depended on age: 5‐8 years = 1 tablet; 9‐12 = 2 tablets; 13‐15 = 3 tablets
Duration of treatment: 4 weeks each arm, then crossed over
Follow up: none possible

Outcomes

Mean wet nights in 4th week: A: 4.1, B: 4.5
No. not achieving 14 dry nights: A: 25/28, B: 27/28
Both arms better than baseline (by 1 wet night per week) but not different from each other

Notes

Data from first arm of trial used
No SDs
Triclofos is a sedative, ephedrine is a stimulant
No washout

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: No (1 had daytime wetting)

Participants

Number of children (boys): 11 (8)
Dropout: 1
Excl: ascertainable organic disease
Previous treatment: 1 resection of bladder neck
Age range 5 to 16 (and one adult aged 31 years)
Baseline wetting: mean number of wet nights per month A:26.7, B:22.0

Interventions

A (10): phenmetrazine (Preludin) 25mg (half tablet for young children; 2 tablets for adults)
B (10): placebo
Duration of treatment: 1 month each arm of the trial
Follow up: none

Outcomes

Mean (SD) number of wet nights per month:
Period 1 A:7.3(7.06), B:11.0(6.83)
Period 2 A:3.3(1.50), B:5.2(6.62)
Period 3 A:1.3(1.75), B:3.8(2.5)

Notes

Very small sample
Groups do not look comparable
Dropout not included in analysis
Includes one adult
No fluid restrictions, diet change or lifting No follow up
No washout and clear carry‐over effect period 1 to 2

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

CCT (alternate allocation to groups)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned

Participants

No. of children: 25 (boys A:6, B:5)
Incl: wetting consistently over 3yrs
Most had previous treatment from other practitioner without any relief
Mean age A:8.9yrs, B:8yrs
Baseline wetting: mean frequency of wetting A:8.8, B:9

Interventions

A (13): tranquillisers ‐ meprobamate (400mg daily and hydroxyzine 1mg kg daily)
B (12): imipramine 25mg daily increased to 50mg in some cases
Duration of treatment: 6 weeks
Follow up: 1 week

Outcomes

Mean (SD) frequency of wetting: A: 6.5 (1.19), B: 1.9 (2.11)
Number totally dry (not defined) A:0, B:5 (2 in A showed some improvement)
Nearly 60% who responded relapsed after discontinuation of the drug
When tranquilliser group given imipramine 5 became totally dry and 6 showed improvement
2 complained of burning sensation

Notes

No details of blinding
No details of dropouts
Age, sex distribution and frequency of bed wetting comparable in groups
Very short follow up
No statistical analysis
No details how progress monitored or when measurements taken

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

High risk

C ‐ Inadequate

Methods

RCT (double‐blind crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: At home

Participants

No. of children (boys): 23 (15)
Incl: primary nocturnal enuresis, no fluid restriction, at least 5 wet nights/month, no current treatment
Excl: urinary tract abnormalities
Previous treatment: no information
Ages: range 6‐15 years

Interventions

A (23): Cetiprin 200 mg (emepronium bromide)
B (23): placebo

Duration of treatment: 6 weeks each arm

Follow up: none

Outcomes

Results given relative to placebo arm: 2.7 more dry nights with Cetiprin than placebo; and 4.3 more dry nights with Cetiprin than during baseline observation (not statistically significant, data not provided).
11/23 children had more dry nights with A than B; 5/23 had the same number on A and B; and 7/23 had fewer.
Adverse events: none
Trialists' conclusion: Cetiprin had no effect

Notes

No useable data
Danish language
Groups comparable at baseline on age and sex
No washout mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

CCT (alternate allocation)
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: A+B clinic attenders and paediatric referrals; C+D residents in Sunland Training Centre, Florida

Participants

No. of children (boys): A+B 10 (8); C+D 8
Incl: C+D had learning difficulties
Excl: organic cause for enuresis
Age: A+B 6‐12 years; C+D 9‐12 years

Interventions

A (5): Alarm + methedrine 5mg
B (5): Alarm only
C (3): Alarm + methedrine 5mg
D (5): Alarm only
Duration of treatment: 8 weeks
Follow up: 13 months

Outcomes

No. not achieving 14 dry nights: A: 0/5, B: 0/5, C: 0/3, D: 4/5

Notes

Groups A+C and B+D combined for analysis
Baseline comparability not mentioned
Drug did not affect outcome but numbers too small to be reliable

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

High risk

C ‐ Inadequate

Methods

RCT
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Yes
Setting: Outpatient Department, Ankara

Participants

No. of children (boys): 73 (42)
Dropouts: 27 other children, dropped out as uncooperative or did not attend for follow up
Incl: nocturnal enuresis
Excl: diurnal enuresis, encopresis, UTI, organic defects
Ages: range 6‐14 years (mean boys 8.5, girls 8.4)

Interventions

A (18): piracetam (20mg/kg at bedtime, maximum 800 mg)
B (15): play and supportive therapy
C (12): both
D (14): placebo (single dose at bedtime)
[E (14): non‐enuretic epileptics treated with diphenylhydantoin 5mg/kg per day]

Duration of treatment: 8 weeks
Follow up: none

Outcomes

No. not achieving 14 dry nights during trial: A: 16/18, B: 8/15, C: 4/12, D: 9/14
Side effects: A: mild headache or nausea, number not specified

Notes

Trialists concluded that piracetam was ineffective

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Department of Paediatrics, Baylor

Participants

No. of children: 50
Incl: nocturnal enuresis
Excl: organic uropathy, mental retardation
Ages 3‐15 years

Interventions

A (28): diazepam 15 mg per day increased to 25 mg if no response
B (22): matching placebo
Duration of treatment: 4 weeks. If poor response then given open label diazepam for 8 weeks, if good response continued on A or B as allocated, therefore follow up not possible

Outcomes

Mean wet nights per week in 4th week: A: 1.04 (SD 2.53), B: 5.91 (2.43)
No. not achieving 14 dry nights during trial: A: 6/28, B: 21/22
Adverse events causing discontinuation: A: 1 (drowsiness, ataxia), B: 1 (insomnia and hyperactivity)

Notes

Results from first 4 weeks only
Baseline comparability of groups not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (double‐blind randomised crossover with 1 week washout)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Yes

Participants

No. of children (boys): 18 (8)
Incl: average of 3 wet nights per week; no diurnal wetting
Previous treatment: no details
Mean age 7.7 years (range 5‐11)
Severity at baseline: mean number of wet nights over 28 days: 19.8

Interventions

A (18): imipramine hydrochloride (25 or 50mg)
B (18): ephedrine sulphate (7.5 or 15mg)
Duration of treatment: 28 days in each condition
Follow up: not specified

Outcomes

Mean number (SD) of wet nights over 28 days: A:9.2 (6.72), B:17.4 (5.8)
5 children became completely dry but all required medication. Eight children were dry >90% of the time with 2 children needing no further medication

Notes

Unclear if intention to treat
Only part of trial (children with no organic causes) included here

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

CCT (double‐blind to children and staff but alternate allocation to groups)
Systematic baseline measure of wetting: Yes
Organic causes excluded: No
Daytime wetting excluded: Not mentioned
Setting: 29 'disturbed boys' from childrens' homes, rest at home in the community

Participants

No. of children: 65 reported
Dropouts: A: 8, B: 9 before start of trial
Incl: at least 2 wet nights/ 2 weeks, age range 5‐15
Baseline wetting: A: mean 5.21/week, B: 4.94

Interventions

A (33): propantheline bromide 15 mg for 4 days, then 30 mg for 4 days, then 45 mg for 6 days
B (32): placebo
Duration of treatment: 2 weeks
Follow up: 4 weeks

Outcomes

Mean wet nights per week during trial: A: 4.7, B: 5.36 (difference stated to be significant, P<0.01)
No. of children cured: none
Mean wet nights per week after trial: A: 4.96, B: 5.33

Notes

No SDs
Propantheline has an anti‐parasympathetic (anti‐cholinergic) action
Groups comparable at baseline on age

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

High risk

C ‐ Inadequate

Methods

RCT (crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Yes

Participants

Number of children (boys): 41 (25)
Dropouts: 11
Incl: history compatable with primary nocturnal enuresis, no history of urinary tract surgery, no urinary tract infection, no daytime wetting
Previous treatment:
4(13%) never had drug therapy
22 treated with imipramine
6 with unknown drugs
Mean age:
boys 9 years 7months
girls 10 years 4months
Baseline wetting: Mean number of wet nights 20 out of 28

Interventions

A (30): oxybutynin (2 x 5mg tablets at supper time)
B (30): identical placebo
Duration of treatment: 28 days in each arm
Follow up: none

Outcomes

Mean difference in frequency of wet nights while taking oxybutynin rather than placebo was ‐1.87 (not significant)
No significant difference between boys and girls (pooled sample variance =56.9, t=0.61, p=0.55) or between those who had previously taken imipramine vs not.
Side effects: 5/30 (stomach discomfort, fatigue, dizziness, headache and dry mouth)

Notes

No useable data
No washout
25% dropped out
Graphical data

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (no details)
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: paediatric urology clinic, Varese, Italy

Participants

Number of children: 58
Dropouts: 0
Incl: severe enuresis (7 wet nights per week)
Excl: organic causes, other illnesses, UTI
Previous treatment: not stated
Ages: 5‐14 years

Interventions

A (29): oxybutynine (5mg 3 times a day)
B (29): dicyclomine (20mg 3 times a day)
Duration of treatment: 4 weeks
Follow up: none (responders continued on the drug, non‐responders received the alternative)

Outcomes

Wet nights in 4th week: A: 1.1 (SD 1.7), B: 6.8 (0.5)
Responders (reduction of 40% in wet nights): A: 26/29, B: 4/29
Side effects: on oxybutinin during trial or afterwards: visual disturbances 29.6%, xerostomia 55.5%, digestive disturbances 18.4%, nausea 16.6%, vertigo 9.2%, tachycardia 7.4%, tachycardia 20%, headache 7.4%. None were serious enough to discontinue treatment

Notes

Data estimated from graph

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

CCT (alternate allocation by last digit of hospital number)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: children's outpatient clinic, Ipswich and East Suffolk

Participants

Number of children (boys): 15 (12)
Incl: consecutive children referred with enuresis
Excl: organic causes
Previous treatment : 4
Ages 3‐15 years (mean A: 6.2, B: 9.4), but only 3 children under 6 years
Baseline wetting: more than half the nights were wet

Interventions

A (9): propantheline 30 mg (1 tablet for 4 weeks, 2 tablets for 4 weeks then crossed over to B
B (6): placebo (matching regime)
Duration of treatment: 12 weeks
Follow up: not possible

Outcomes

Mean wet nights during trial: A: 2.11, B: 1.75
No. not achieving 14 dry nights: A: 2/9, B: 1/6
Side effects: A: 2 (dry mouth), B: 1 (dry mouth)

Notes

No SDs
Data from parallel group arms
All children also received routine management including avoidance of blame, rewards for dry nights and fluid restriction
Control group older and had more wet nights at baseline

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

High risk

C ‐ Inadequate

Methods

RCT (double‐blind)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned

Participants

No. of children 88 (boys 62%)
Dropouts: 47
Previous treatment: no details
Age range: 4‐13 years
Average age: 8 years
Severity of wetting at baseline: mean percentage of bed wetting frequency A:77%, B:81%, C:79%

Interventions

A (41): furosemide (Lasix) 40mg
B (43): imipramine 25mg
C (44): placebo
Doses increased if no response
Duration of treatment: 4 weeks
Follow up: 1 year

Outcomes

At end of study mean percentage wet nights per week: A: 73%, B: 49%, C: 67%
When followed up after 1 year, 59 children had increased frequency of wetting to baseline level or worse

Notes

Danish paper
No SDs
No details of reasons for dropouts

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

CCT (randomisation using case record numbers)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Yes
Setting: St Petersburg State Medical Academy, Russia

Participants

No. of children: 62 (43 boys) plus 22 (15) on placebo
Incl: primary nocturnal enuresis
Excl: other medication, daytime wetting, other disease
Age range 6‐15 years (mean 9.8 +/‐ 7)
Baseline wetting at least 6 wet nights per 2 weeks

Interventions

A (32): desmopressin 10.5 ‐ 24.5 mcg intranasally
B (30): diclofenac tablet 1 mg/kg body mass
C (22): Placebo (intranasally) for 2 weeks then given desmopressin
Duration of treatment: A and B 4 weeks each, C (placebo) 2 weeks only
Follow up: none

Outcomes

No. not achieving 14 dry nights: A: 11/32; B: 20/30; C: 21/22
Side effects: none reported

Notes

Extra information supplied by authors (method of randomisation, results confirmed, no side effects)
Parallel groups

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

High risk

C ‐ Inadequate

Methods

RCT (randomised double‐blind crossover)
Systematic baseline measure of wetting: No
Organic causes excluded: No
Daytime wetting excluded: No
Setting: Outpatient clinic

Participants

No. of children: 69
Dropouts: 7
Incl: primary and secondary enuresis, some diurnal wetting, organic causes or behavioural disturbances
Excl: none
Previous treatment: almost all (waking, alarms, drugs, hospital admission)
Ages: 5‐15 years (mean for boys 8 years 6 months, girls 8 years 3 months)

Interventions

A (61): imipramine
B (61): imipramine‐N‐oxide
C (61): emepronium (cetiprin)
D (61): placebo
(all matching preparations)
Duration of treatment: 4 weeks on each drug
Follow up: children continued on one successful drug for 3 months: A: 32 children, B: 10, C: 2, D: 4

Outcomes

Mean wet nights per week in last 3 weeks of each drug: A: 2.4, B: 3.24, C: 4.36, D: 4.37
Adverse events: A: 13, B: 7, C: 10, D: 11 (nausea, decreased appetite, sleep disturbance, rash, headaches, sweating, fatigue, sullenness, tremor)

Notes

No SDs
No washouts
All children had fluid restriction and wakening once a night

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (double‐blind crossover trial)
Systematic baseline measure of wetting: No
Organic causes excluded: No
Daytime wetting excluded: Not mentioned
Setting: hospital enuresis clinic

Participants

No. of children: Trial 1: 53, Trial 2: 24
Incl: consecutive children with primary nocturnal enuresis, age over 5.5 years

Interventions

Trial 1
A ( 53): oxazepam ('Serenid') 10 mg 2x or 3x/day
B (53): placebo

Trial 2
C (24): chlordiazepoxide ('Librium') 10 mg 3x/day
D (23): placebo
Duration of treatment, trial 1: 2 months each arm

Outcomes

Trial 1: 'an increase in dry nights with A only slightly greater than with Placebo B'
Trial 2: C 'during the day gave a statistically significant improvement (P<0.001) compared with placebo D'

Notes

No useable data

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (method not specified)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned

Participants

No. of children: 85
Incl: primary enuresis, age >5yr
Excl: enuresis treatment, other disease symptoms
Age range 6‐15, mean 8 years
Baseline wetting at least 3 wet nights/week
Dry nights in 2 weeks: A: 1.5 (SE 0.3); B: 1.5 (0.4); C: 1.1 (0.3)

Interventions

A (31): desmopressin 20 mcg, intranasally
B (29): indomethacin 100 mg/day, suppository
C (25): placebo
Duration of treatment: 4 weeks
Follow up: none

Outcomes

Mean DRY nights/2 weeks (SE) on treatment: A: 31, 11.8 (0.5); B: 29, 8.9 (0.8); C: 25, 3.8 (0.8)
[= wet nights per week: A: 31, 1.1 (SD 1.39); B: 29, 2.55 (2.15); C: 25, 5.1 (2)]
Side effects: none reported

Notes

Parallel groups
Blinding not possible due to different routes of administration

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (double‐blind crossover trial)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: referrals from local authority enuresis clinic to Dept Psychiatry, New York

Participants

No. of children (boys): 14 (6)
Dropouts: 8 (4 not wet enough, 4 other reasons)
Incl: school age, wet at least 8 nights /2 weeks
Ages: mean 8 years, 3 months, range 4,7 to 12,2

Interventions

A (14): Indoramin 20 mg
B (14): Indoramin 10 mg
C (14): placebo
Duration of treatment: 2 weeks in each arm

Outcomes

Mean DRY nights in 2 weeks: A: 3.61, B: 4.03, C: 3.3
'no significant differences or order effects'
Trialists' conclusion: alpha blockade does not improve enuresis

Notes

Indoramin = alpha‐adrenoceptor blocker
No washout phase
No SDs

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

RCT (double‐blind, parallel groups, placebo controlled randomised trial)
Method of allocation or concealment not described
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: No
Setting: outpatient trial in more than one centre

Participants

No. of children (boys): 87 (64)
Dropouts: A: 9/44, B: 9/43
Incl: nocturnal enuresis, washout period after excluded medications
Ages (mean years): A: 10.22 (SD 2.02), B: 9.12 (1.89) P=0.011, Group A children significantly older than Group B
Baseline wetting (mean dry nights per week): A: 1.51, B: 1.01 (A significantly more dry nights)

Interventions

A (44): atomoxetine, increasing dose over first 3 days until 1.5 mg/kg in 2 divided doses
B (43): matching placebo
Duration of treatment: 12 weeks
Folow up: none

Outcomes

Dry nights per week (mean): A: 2.98, B: 1.61 (P= 0.010)
Number of children with no wet nights in last week of treatment: A: 8/42, B: 0/41
Adverse effects causing discontinuation: A: 2/44, B: 1/43
Weight change: A: 0.45 kg loss, B: 1.08 gain
Increased pulse rate to over 20 beats per minute: A: 6/44, B: 0/43

Notes

Research funded by drug company
Groups not comparable at baseline on number of dry nights (A better), age (A older), number of children with attention‐deficit /hyperactivity disorder (A fewer)
No SDs
Atomoxetine is an inhibitor of the presynaptic norepinephrine transporter, i.e. it has an adrenergic agonist effect

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (divided at random into 4 groups)
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Yes
Setting: Dept Urology, Military Medical Faculty, Turkey

Participants

No. of children (boys): 77 (48)
Dropouts: A: 2, B: 7, C: 2, D: 9 (not explained)
Incl: primary nocturnal enuresis, >= 3 wet nights/week, no current treatment
Excl: organic causes, daytime wetting, UTI
Ages: 6‐14 years (9.44 +/‐ 2.17)

Interventions

A (14): imipramine 0.9‐1.5 mg/kg/day
B (16): oxybutynin 5 mg 3x/day
C (24): imipramine + oxybutynin
D (23): placebo (not described)
If cured, treatment tapered off gradually
Duration of treatment: 3 months
Follow up: 6 months

Outcomes

Cure defined as >90% reduction in wet nights
Failed: A: 7/14, B: 10/16, C: 8/24, D: 18/23
Failed or relapsed: A: 10/12, B: 8/9, C: 10/22, D: 11/14
Side effects: A: 3/14 (dry mouth, nausea), B: 4/16 (dry mouth, nausea), C: 7/24, D: 4/23

Notes

Groups comparable at baseline on age, sex and disease severity but groups of unequal sizes
No details of previous treatment
No details of nature of placebo treatment
Cure not defined as complete dryness

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT
Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Dept Paediatric Nephrology, Turkey

Participants

No. of children: 29
Incl: primary nocturnal enuresis for 6 months, age over 5 years, at least 3 wet nights in last 2 weeks
Excl: neurological or renal disease, dry period for more than 6 months
Ages: 6‐15 years (mean A: 10.8, B: 8.6, C: 9)
Baseline dry nights in 2 weeks: A: 2.4 (SD 2.2), B: 2.5 (2.2), C: 2 (2.3)

Interventions

A (9): oxybutynin 0.5 mg/kg
B (11): pseudoephedrine 2 mg/kg
C (9): indomethacin 2 mg/kg
Duration of treatment: 4 weeks
Follow up: none

Outcomes

Mean DRY nights in 2 weeks: A: 4.7 (SD 3.9), B: 6.2 (3.8), C: 4.3 (4)
[= wet nights per week: A: 9, 4.65 (SD 1.95); B: 11, 3.9 (1.9); C: 9, 4.85 (2)]
Adverse events: A: 3 epistaxis, 1 flushing, 1 voiding difficulty, B: none, C: 1 gastrointestinal irritation

Notes

Groups comparable at baseline on age, urinalysis, dry nights, family history, socioeconomic conditions, but group A older

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Belfast hospital

Participants

No. of children (boys): 300 (167)
Dropouts: 67 (A: 22, B: 28, C: 17)
Incl: ages 4‐14, wet at least 6x/week for at least 1 year
Ages: 4 years 11 months to 14 years

Interventions

A (78): propantheline (3 x 15mg)
B (72): propantheline (3 x 15mg) + phenobarbitone (15mg)
C (83): placebo (3 x)
Duration of treatment: 4 months (reducing dose by 1 tablet a week in last 2 months)
Follow up: none

Outcomes

No. cured: A: 7/78, B: 10/72, C: 6/83
No. 50% improved: A: 18/78, B: 15/72, C: 19/83
Toxic effects caused dropout in 12 children (A: 4 headache, dry mouth, B: 8 headache, dry mouth, skin rash, C: 0 causing dropout but several had headache, abdominal pain, vertigo)

Notes

Groups comparable at baseline on age, sex
Propantheline is an anti‐cholinergic, phenobarbitone is a sedative

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (medications on double‐blind basis)

Systematic baseline measure of wetting: Yes
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned

Participants

No. of children: 23
Dropouts: A: 0 B: 0 C: 2 D: 0

Age range 4 to 10 years
Baseline wetting: mean number of wettings per week: A + B: 4.9 C: 3.0 D: 6.6

Interventions

A (3): amphetamine sulphate (2.5mg)
B (5): ephedrine sulphate (75mg) + atropine sulphate (Enuretrol, 1.15mg)
C (5): placebo twice daily
D (10): enuresis alarm

Duration of treatment: 5 weeks

FU after 4 weeks

Outcomes

Mean number of wet nights in final week of treatment: A+B:4.1, C:3.5, D:1.7

Notes

No SDs
Data estimated from graph
Groups seem very different at baseline
More likely to detect more wettings per night in pad and bell group
All active drugs groups combined
No details of inclusion\exclusion criteria

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

RCT (groups randomly assigned)
Systematic baseline measure of wetting: No
Organic causes excluded: Yes
Daytime wetting excluded: Not mentioned
Setting: Paediatric OP, Ankara, Turkey

Participants

No. of children (boys): 41 (25)
Incl: age at least 6 years, suitable for drug treatment, nocturnal enuresis
Excl: urine abnormality
Previous treatment: most had failed with simple methods such as waking or fluid restriction
Ages: 6‐16 years (mean 11 years)

Interventions

A (14): imipramine 25mg
B (8): amitriptyline25 mg
C (10): chlordiazepoxide clinidium 5mg/2.5mg
D (9): piracetam 400 mg
Duration of treatment: 6 weeks

Outcomes

Imipramine significantly better than amitriptyline, chlordiazepoxide clinidium and piracetam on therapeutic index score: A: 1.57, B: 1.25, C: 1.3, D: 0.33

Notes

No useable data
Groups comparable at baseline on age and social class

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear