Alarm interventions for nocturnal enuresis in children · 2013-04-23 · Verhulst 1985). Although enuresis shows a steady decline with age, 2 to 3% still wet regularly during the

Alarm interventions for nocturnal enuresis in children

(Review)

Glazener CMA, Evans JHC, Peto RE

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2009, Issue 1

http://www.thecochranelibrary.com

Alarm interventions for nocturnal enuresis in children (Review)

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

21CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

71DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 ALARM vs CONTROL, Outcome 1 Mean number of wet nights per week. . . . . 77

Analysis 1.3. Comparison 1 ALARM vs CONTROL, Outcome 3 Number not achieving 14 consecutive dry nights. 79

Analysis 1.4. Comparison 1 ALARM vs CONTROL, Outcome 4 Numbers not achieving 14 dry nights or relapsing. 81

Analysis 2.1. Comparison 2 COMPARING ALARMS, Outcome 1 Mean number of wet nights per week. . . . . 82

Analysis 2.3. Comparison 2 COMPARING ALARMS, Outcome 3 Numbers not achieving 14 dry nights. . . . . 83

Analysis 2.4. Comparison 2 COMPARING ALARMS, Outcome 4 Numbers not achieving 14 dry nights or relapsing. 85

Analysis 3.1. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 1 Mean number of wet nights

per week. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

Analysis 3.3. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 3 Numbers not achieving 14

dry nights. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

Analysis 3.4. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 4 Mean number of wet nights

at follow-up. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Analysis 3.5. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 5 Numbers not achieving 14

dry nights or relapsing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Analysis 4.1. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 1 Mean number of

wet nights per week. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Analysis 4.3. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 3 Number not

achieving 14 consecutive dry nights. . . . . . . . . . . . . . . . . . . . . . . . . . . 91

Analysis 4.4. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 4 Numbers not

achieving 14 dry nights or relapsing. . . . . . . . . . . . . . . . . . . . . . . . . . . 93

Analysis 4.5. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 5 Mean number of

wet nights at follow-up. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

Analysis 5.1. Comparison 5 ALARM vs DRUGS, Outcome 1 Mean number of wet nights per week. . . . . . . 96

Analysis 5.3. Comparison 5 ALARM vs DRUGS, Outcome 3 Numbers not achieving 14 dry nights during treatment. 98

Analysis 5.5. Comparison 5 ALARM vs DRUGS, Outcome 5 Number not achieving 14 dry nights or relapsing. . . 100

Analysis 5.6. Comparison 5 ALARM vs DRUGS, Outcome 6 Mean number of wet nights at follow-up. . . . . . 101

Analysis 6.1. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 1 Mean number of

wet nights per week. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

Analysis 6.3. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 3 Numbers not

achieving 14 dry nights. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

Analysis 6.4. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 4 Number not

achieving 14 dry nights or relapsing. . . . . . . . . . . . . . . . . . . . . . . . . . . 103

103WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

103HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

104CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

104DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

104SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

105INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iAlarm interventions for nocturnal enuresis in children (Review)


[Intervention Review]

Alarm interventions for nocturnal enuresis in children

Cathryn MA Glazener1, Jonathan HC Evans2, Rachel E Peto3

1Health Services Research Unit, University of Aberdeen, Aberdeen, UK. 2Department of Paediatric Nephrology, Nottingham University

Hospitals NHS Trust, Nottingham, UK. 3NHS Centre for Reviews & Dissemination, University of York, York, UK

Contact address: Cathryn MA Glazener, Health Services Research Unit, University of Aberdeen, 3rd Floor, Health Sciences Building,

Foresterhill, Aberdeen, Scotland, AB25 2ZD, UK. [email protected].

Editorial group: Cochrane Incontinence Group.

Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.

Review content assessed as up-to-date: 27 February 2007.

Citation: Glazener CMA, Evans JHC, Peto RE. Alarm interventions for nocturnal enuresis in children. Cochrane Database of SystematicReviews 2005, Issue 2. Art. No.: CD002911. DOI: 10.1002/14651858.CD002911.pub2.


A B S T R A C T

Background

Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15 to 20% of five year olds, and up to 2%

of young adults.

Objectives

To assess the effects of alarm interventions on nocturnal enuresis in children, and to compare alarms with other interventions.

Search methods

We searched the Cochrane Incontinence Group Specialised Trials Register (searched 28 February 2007) and the reference lists of relevant

articles.

Selection criteria

All randomised or quasi-randomised trials of alarm interventions for nocturnal enuresis in children were included, except those focused

solely on daytime wetting. Comparison interventions included no treatment, simple and complex behavioural methods, desmopressin,

tricyclics, and miscellaneous other methods.

Data collection and analysis

Two reviewers independently assessed the quality of the eligible trials, and extracted data.

Main results

Fifty six trials met the inclusion criteria, involving 3257 children of whom 2412 used an alarm. The quality of many trials was poor,

and evidence for many comparisons was inadequate. Most alarms used audio methods.

Compared to no treatment, about two thirds of children became dry during alarm use (RR for failure 0.38, 95% CI 0.33 to 0.45).

Nearly half who persisted with alarm use remained dry after treatment finished, compared to almost none after no treatment (RR of

failure or relapse 45 of 81 (55%) versus 80 of 81 (99%), RR 0.56, 95% CI 0.46 to 0.68). There was insufficient evidence to draw

conclusions about different types of alarm, or about how alarms compare to other behavioural interventions. Relapse rates were lower

when overlearning was added to alarm treatment (RR 1.92, 95% CI 1.27 to 2.92) or if dry bed training was used as well (RR 2.0, 95%

1Alarm interventions for nocturnal enuresis in children (Review)


mailto:[email protected]

CI 1.25 to 3.20). Penalties for wet beds appeared to be counter-productive. Alarms using electric shocks were unacceptable to children

or their parents.

Although desmopressin may have a more immediate effect, alarms appeared to be as effective by the end of a course of treatment

(RR 0.85, 95% CI 0.53 to 1.37) but their relative effectiveness after stopping treatment was unclear from two small trials which

compared them directly. Evidence about the benefit of supplementing alarm treatment with desmopressin was conflicting. Alarms were

not significantly better than tricyclics during treatment (RR 0.59, 95% CI 0.32 to 1.09) but the relapse rate was less afterwards (7 of

12 (58%) versus 12 of 12 (100%), RR 0.58, 95% CI 0.36 to 0.94). However, other Cochrane reviews of desmopressin and tricyclics

suggest that drug treatment alone, while effective for some children during treatment, is unlikely to be followed by sustained cure as

almost all the children relapse.

Authors’ conclusions

Alarm interventions are an effective treatment for nocturnal bedwetting in children. Alarms appear more effective than desmopressin

or tricyclics because around half the children remain dry after alarm treatment stops. Overlearning (giving extra fluids at bedtime after

successfully becoming dry using an alarm), dry bed training and avoiding penalties may further reduce the relapse rate. Better quality

research comparing alarms with other treatments is needed, including follow-up to determine relapse rates.

P L A I N L A N G U A G E S U M M A R Y

Alarm interventions for nocturnal enuresis (bedwetting) in children

Night-time bedwetting is common in childhood, and can cause stigma, stress and inconvenience. The review of trials found 56 studies

involving 3257 children. Alarm interventions reduce night-time bed wetting in about two thirds of children during treatment, and

about half the children remained dry after stopping using the alarm. Alarms take longer to reduce bedwetting than desmopressin, but

their effects continue after treatment in half the children who use alarms. So alarms are better in the long term than treatment with

desmopressin or tricyclic drugs. Overlearning (giving children extra fluids at bedtime after successfully becoming dry using an alarm)

and dry bed training (getting children to go to the toilet repeatedly and changing their own sheets when they wet) may reduce the

relapse rate. There are no serious side-effects, which can occur with drug treatment. However, children need more supervision and time

from other family members at first. There was not enough evidence with which to compare alarms with other non-drug treatments.

Because some of the studies were of poor quality, better research comparing alarms with other treatments is needed, including follow-

up to measure relapse rates.

B A C K G R O U N D

This is one of seven reviews of interventions for bedwetting,

or non-organic nocturnal enuresis. The others focus on: desmo-

pressin (Glazener 2002), tricyclics and related drugs (Glazener

2003a), other drugs (Glazener 2003b), simple behavioural train-

ing (Glazener 2004b), complex behavioural training (Glazener

2004b) and complementary and miscellaneous other interventions

(Glazener 2005b). All seven are based on the work of Lister-Sharp

and her colleagues at the Centre for Reviews and Dissemination at

the University of York, UK (Lister-Sharp 1997). The current re-

view is a further update of previously published Cochrane reviews

(Glazener 2001; Glazener 2003c; Glazener 2005a). It concerns

the use of alarms triggered by wetting (e.g. pad-and-bell alarms)

to waken the child. It is restricted to children with monosymp-

tomatic nocturnal enuresis who are treated with an alarm triggered

by wetting, and includes other interventions if they are compared

with such alarms or used in combination with them.

Nocturnal enuresis is the involuntary loss of urine at night, in the

absence of organic (physical) disease such as urinary tract infection

or detrusor overactivity, at an age when a child could reasonably

be expected to be dry (by consensus, at a developmental age of

five years) (APA 1980; WHO 1992). Although bedwetting in it-

self is pathologically benign and has a high rate of spontaneous

remission, it may bring social and emotional stigma, stress and

inconvenience to both the person with enuresis and their fami-

lies (Fitzwater 1992). Children who wet the bed may experience

parental disapproval, sibling teasing and repeated treatment failure



which may lower self esteem (Warzak 1992). The children may

also be at increased risk of emotional and physical abuse (Warzak

1992). Consequently, it is important that enuresis is properly man-

aged (Moffatt 1994).

Although daytime wetting is a significant problem and is often

associated with bedwetting, it is usually considered separately. It

has been suggested that there are different aetiologies underly-

ing monosymptomatic nocturnal enuresis and daytime wetting

(Jarvelin 1989). If daytime symptoms are present, investigations

to identify physical causes such as urinary tract dysfunction, con-

genital malformation and neurogenic disorders are usually neces-

sary (Djurhuus 1992). An organic cause is more often found in

children with daytime wetting; for example more structural ab-

normalities and functional disorders of the urinary tract are found

in daytime wetters than controls (Jarvelin 1990).

Prevalences and causes

Nocturnal enuresis is a complaint that affects many families. Es-

timating the prevalence of monosymptomatic nocturnal enuresis

is difficult, however, because there is variation in methods of di-

agnosis and definitions (de Jonge 1973; Krantz 1994). About 13

to 19% of boys and 9 to 16% of girls at age five wet the bed at

least once per month (Devlin 1991; Feehan 1990; Rutter 1973;

Verhulst 1985). Although enuresis shows a steady decline with

age, 2 to 3% still wet regularly during the late teens and early

adulthood (Forsythe 1974). The incidence of nocturnal enuresis

is particularly high amongst children in residential care (Morgan

1970). Without treatment, about 15% of bedwetting children be-

come dry each year (Forsythe 1974). However, it is not possible

to predict which children will become dry spontaneously (Doleys

1977).

The causes of monosymptomatic nocturnal enuresis are unclear

(Lister-Sharp 1997). Genetic (APA 1980; Bakwin 1971; Bakwin

1973; Eiberg 1995), physiological (Djurhuus 1992; Norgaard

1993) and psychological (Devlin 1991; Rutter 1973; Shaffer 1977;

Moffatt 1989) factors, as well as delay in maturation of the mech-

anism for bladder control (Jarvelin 1989; Koff 1995), have been

suggested. Other factors which may contribute to bedwetting in-

clude: constipation, sleep apnoea and upper airway obstructive

symptoms (Maizels 1993); and diet and mild caffeine drinks with

diuretic effects (e.g. cola) (Blackwell 1989).

Interventions

Pharmacological, psychological/behavioural and a variety of ’un-

conventional’ interventions are commonly used for people who

wet the bed.

• Pharmacological interventions include desmopressin

(Glazener 2002), tricyclic drugs (amitriptyline, dothiepin,

doxepin, trimipramine, clomipramine, desipramine, imipramine,

lofepramine, nortriptyline and protriptyline, Glazener 2003a),

drugs related to the tricyclics (viloxazine, desipramine, mianserin

and maprotiline, Glazener 2003a), and a variety of other drugs

(e.g. amphetamine, diazepam and oxybutynin, Glazener 2003b).

These are discussed in separate reviews as indicated.

• Behavioural interventions include simple methods (e.g. star

charts, reward systems, overlearning, retention control training,

urine stream interruption exercises, lifting and scheduled

wakening, Glazener 2004b), and complex (multidimensional)

behavioural methods (e.g. dry bed training, full spectrum home

training, Glazener 2004a).

• Other interventions include psychotherapy, surgery, fluid

deprivation and complementary therapies (review in

preparation).

Enuresis alarms

Enuresis alarms consist of some kind of alarm which is activated

by micturition. The first enuresis alarms were bed-based, the child

sleeping on a pad or mat containing an electrical circuit (Mowrer

1938). Urine, coming into contact with this would complete the

circuit causing a bell to ring. Historically, some alarms worked

by giving an electric stimulus or shock to the children’s skin. The

alarm is intended to change the meaning of the sensation of having

a full bladder from a signal to urinate to a signal to inhibit urination

and waken (Forsythe 1989). There are now many variations: the

alarm may be a bell, buzzer, a visual signal such as a light or it

may vibrate. There are also many different tones and intensities,

and the alarm may be set to operate only intermittently or after

an interval. In ’mini-alarm’ systems, the sensor is placed in pants,

producing a discrete, portable system (’body-worn’ alarm).

Overlearning

An over-learning procedure may be initiated after successful alarm

treatment (e.g. achievement of 14 consecutive dry nights). Extra

drinks are given at bed-time to cause additional stress to the de-

trusor muscles in the bladder. Alarm treatment is then continued

until 14 consecutive dry nights are once again achieved (Blackwell

1989).

Other behavioural interventions

These include:

Lifting

Lifting involves taking the child to the toilet during the night to

empty their bladder, usually before the time that bedwetting is

expected, without necessarily waking the child.



Waking

This intervention involves waking the child to allow them to get

up and urinate (Warzak 1994). A scheduled waking programme

may be used with the child being woken progressively earlier after

dry nights until the interval between going to bed and scheduled

waking is one hour. Older individuals may use an alarm clock to

wake themselves (Blackwell 1989). However, the use of an alarm

clock in this circumstance is not included as an alarm triggered by

bedwetting as defined in this review.

Reward systems (e.g. star chart)

Systems to reward the child for dry nights are often used as first

line treatment. For example, the child might receive a star for every

dry night, and a reward after a preset number of stars have been

earned.

Retention control training

This is an attempt to increase the functional bladder capacity using

exercises such as delaying urination for extended periods of time

or drinking increased fluids (Warzak 1994).

Stop-start training

Stream interruption exercises (pelvic floor muscle training) have

also been used (Novello 1987).

Dry bed training

Dry bed training was initially developed in the early 1970s for use

with people with learning disabilities (Azrin 1973). The original

schedule involved an intensive training night, during which the

patient was woken every hour and taken to the toilet. If an accident

occurred, 45 minutes of ’cleanliness training’ (changing the bed)

and ’positive practice’ (child practices getting up and going to the

toilet about nine times) was implemented. On subsequent nights,

the individual was woken once and taken to the toilet, this nightly

wakening occurring progressively earlier. The wakening might or

might not be triggered by an alarm.

Other (miscellaneous) interventions in the current review include:

cognitive therapy, psychotherapy, counselling, education/informa-

tion systems, restricted diet and shaming. These are described in

the Table of Included Studies.

The wide variety of treatments for nocturnal enuresis indicates the

lack of consensus as to which is the best. Provided that a sufficient

number of adequate quality have been conducted, the most reli-

able evidence is likely to come from consideration of all well-de-

signed randomised controlled trials. Hence, there is a need for an

easily accessible, periodically updated, comprehensive systematic

review of such studies which will not only help to identify optimal

practice, but also highlight gaps in the evidence base.

O B J E C T I V E S

To determine the effects of alarms for the treatment of children

with nocturnal enuresis.

The following hypotheses were tested:

1. alarms are better than no active treatment/non-functioning

alarms;

2. one type of alarm is better than another one;

3. alarm treatment alone is better than a behavioural intervention

alone;

4. alarm treatment alone is better than alarm treatment supple-

mented by a behavioural method;

5. alarm treatment alone is better than a drug treatment alone or

better than alarm treatment supplemented by a drug;

6. alarm treatment alone is better than treatments other than be-

havioural or drugs.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Randomised or quasi-randomised trials of alarm interventions for

the treatment of non-organic nocturnal enuresis.

Types of participants

Children (as defined by the trialists, usually up to age 16) suffering

from nocturnal enuresis. Trials which included children suffering

from daytime enuresis or where some children may have had an

organic cause contributing to their enuresis were only included if

the primary problem was nocturnal enuresis.

Types of interventions

Any trial which used an alarm in at least one arm of the study.

Comparisons were made with no active treatment, behavioural in-

terventions and drugs (either alone or in combination with alarms)

and any other treatments not already specified.



Types of outcome measures

The outcomes considered in this review were:

• change in the mean number of wet nights per week during

treatment;

• number of participants failing to attain 14 consecutive dry

nights;

• mean number of wet nights per week when participants

were followed up after treatment had ceased;

• number failing to attain 14 consecutive dry nights or

subsequently relapsing; and

• adverse events.

Timing of relapse and follow up was as defined by the trialists.

Search methods for identification of studies

This review has drawn on the search strategy developed for the In-

continence Review Group. Relevant trials were identified from the

Group’s Specialised Register of controlled trials which is described

under the Incontinence Group’s details in The Cochrane Library (For more details please see the ‘Specialized Register’ section of

the Group’s module in The Cochrane Library). The register con-

tains trials identified from MEDLINE, CINAHL, the Cochrane

Central Register of Controlled Trials (CENTRAL) and hand

searching of journals and conference proceedings. Date of the most

recent search of the register for this review: 28 February 2007.

The trials in the Incontinence Group Specialised Register are also

contained in CENTRAL. The terms used to search the Inconti-

nence Group Specialised Trials Register are given below:

(TOPIC.URINE.ENURESIS*)

AND

({DESIGN.CCT*} OR {DESIGN.RCT*})

(All searches were of the keyword field of Reference Manager 9.5

N, ISI ResearchSoft).

The review authors also searched the reference lists of relevant

articles. We did not impose any language or other restrictions on

any of these searches.

Data collection and analysis

The studies for this review were assessed using the methods of the

Cochrane Collaboration (Deeks 2006).

Identification of primary studies

The titles and where possible abstracts of all studies located by the

searches were checked to identify those likely to be evaluations

of the effects of interventions for nocturnal enuresis. Full papers

were then obtained and assessed to identify those which met the

inclusion criteria.

Quality assessment

A range of both general and more specific quality issues were noted,

including:

• the level of concealment of random allocation in the trials

(A=adequate method of concealment of allocation to groups, B=

unclear, C=quasi-randomised, Deeks 2006);

• whether data to assess the comparability of groups at

baseline were given, including baseline levels of wetting;

• use of a ’wash-out’ period if a crossover design was

employed;

• intention-to-treat analysis;

• whether outcomes were clearly defined;

• blinding;

• a follow-up of at least three months or provision of follow-

up data;

• whether useful data (e.g. means and standard deviations)

were presented;

• whether children with daytime wetting were specifically

excluded;

• whether children who had physical (organic) causes for

their enuresis were specifically excluded.

However, none of these criteria were used to include or exclude

trials.

Data extraction

The data were extracted using a standard form, independently by

two review authors.

Data analysis

Where appropriate, the results were converted to the mean and

standard deviation of the number of WET nights per WEEK, or

the number of children failing to achieve cure during treatment,

defined as 14 consecutive dry nights, or the number who were

not cured during treatment plus those who relapsed after stopping

active treatment (to allow for possible differences in initial ’suc-

cess’ rates). Where a mean value was reported with no standard

deviation, we entered the data into ’Other Data Tables’.

We intended, where possible, to calculate standardised effect sizes

and 95% confidence intervals (CI): weighted mean differences

(WMD) where outcomes were continuous variables and relative

risks (RR) where they were binary. A fixed effect model was used

to calculate the pooled estimates and the 95% CIs (Berlin 1989).

The weighted mean differences were weighted by the inverse of

the variance, and given as differences in number of wet nights per

week. Negative values indicate fewer wet nights in the group on

the left of the MetaView.

Differences between trials were further investigated when statis-

tically significant heterogeneity was apparent either at the 10%

probability level, using the chi squared test or assessment of the I-

squared statistic (Higgins 2003), or from visual inspection of the



http://www.mrw.interscience.wiley.com/cochrane/clabout/articles/INCONT/frame.html

















results. If there was no obvious reason for the heterogeneity, or it

persisted despite the removal of outlying trials, a random effects

model was used.

Crossover trials were marked with the suffix ’#’. Data from the

one trial identified were entered into ’Other Data Tables’.

In general, dropouts were not taken into account and data were

presented as given in the trial reports. However, if there were ev-

idence of differential dropouts from the groups which may have

been caused by adverse effects of the interventions, the data were

recalculated as if the dropouts were failures.

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies; Characteristics of ongoing studies.

Eighty four studies were identified as including an alarm interven-

tion. Thirty were excluded, the majority because they were not

randomised controlled trials. Three of these 30 were RCTs which

included an adult population (Azrin 1973; Crisp 1984; Hanson

1988) and one other was excluded because children were switched

between groups (McConaghy 1969). One of these trials was an ’in-

cluded study’ in a previous version of this review (Hanson 1988).

Details are given in the Table of Excluded Studies.

Fifty six randomised controlled trials were included in the review

(see Table of Included Studies). They were described in 52 reports

(three reports each described two trials (Bollard 1981a; Bollard

1981b; Butler 1990a; Butler 1990b; Geffken 1986a; Geffken

1986b), and one described three trials (Lovibond 1964a; Lovibond

1964b; Lovibond 1964c)). One study (reported here as two sepa-

rate trials) divided children into two groups according to their base-

line maximal functional bladder capacity, large or small (Geffken

1986a; Geffken 1986b).

Trials with methodological flaws

Two included trials failed to provide reliable data, one because

groups were combined and results reported only as medians for

the combined groups (Azrin 1974) and the other because children

who dropped out from the alarm groups (due to inability to use

the alarm or family disruption) were replaced by other children

resulting in non-randomised groups and unreliable data (Turner

1970). No data from these trials have been used in the review.

Types of interventions

The trials all included an alarm which activated a bell or buzzer

when triggered by wetting. In the majority, this was the stan-

dard bed-pad-and-bell but variations included body-worn alarms

(Butler 1990a) and electric shock alarms (Elinder 1985; Hojsgaard

1979; Lovibond 1964a; McKendry 1975; Netley 1984).

Numbers of children

In total, 3257 children were studied, of whom 2412 received an

alarm intervention either alone or in combination with another

treatment. In general, sample sizes were small, ranging from 14 to

222 with an average of about 57 participants per trial.

Duration of treatment

Duration of treatment varied amongst the trials: alarms were used

for between two and eight weeks in 16 trials, eight to 12 weeks in 18

trials, and for more than 12 weeks in 22 trials. However, children

usually stopped earlier than the maximum allowed duration of

treatment if they became dry.

Baseline wetting, organic causes and daytime wetting

In 14 trials, there was no period of baseline recording of wetting

before beginning the trial. In seven trials, authors failed to report

that children with a possible organic cause for their bedwetting

were excluded. In one of these seven, neither of these measures

of quality (baseline wetting or exclusion of organic causes) were

recorded (Forrester 1964). Of the seven trials where organic causes

were not specifically excluded, two included some children with

daytime wetting (Caceres 1982; Moffatt 1987), three failed to

record information about daytime wetting (Forrester 1964; Houts

1986; van Londen 1993) and only two explicitly excluded chil-

dren whose primary problem was daytime wetting (Bennett 1985;

Lynch 1984). However, no trials included children with known

organic causes.

In 19 trials, children with diurnal (daytime as well as night-

time) wetting were specifically excluded. Six trials included at least

some children with daytime wetting (Bradbury 1995; Caceres

1982; Gibb 2004; McKendry 1975; Moffatt 1987; Taylor 1975)

although in three, organic causes were specifically excluded

(Bradbury 1995; McKendry 1975; Taylor 1975). Another in-

cluded diurnal wetting ’only if negligible’ (Bennett 1985). One

trial included some children who also had encopresis (Taylor

1975). The remaining trials did not mention daytime wetting.

Follow up

Of the 56 included studies, only 29 trials provided follow-up data

about wet nights or relapse rates after the end of trial treatment.

In some trials follow up was not possible because children were

given alternative (non-randomised) treatments.



Settings

The children were recruited in different settings. In six trials, they

were identified from the community by advertising in the media;

in 18 they were recruited in hospital or community outpatient

clinics; in four both methods were used; three trials were in resi-

dential institutions (Jehu 1977) or amongst children with special

needs (Kennedy 1968; Sloop 1973); and in 22 the setting was not

specified.

Ages of children

Most trials required children to be at least five years old at entry,

but in six trials a few younger children were included (Azrin 1974;

Azrin 1978; Jehu 1977; Taylor 1975; Wright 1974; Young 1972).

Previous treatment

In four trials, children were only included if they had not previously

had treatment for their enuresis (Butler 1990a; Faraj 1999; Ng

2005; Sloop 1973); in another four, all the children had failed

with previous treatment (Butler 1990b; Caceres 1982; Gibb 2004;

Scholander 1968); in a further 16 trials some children had received

previous treatment (Bollard 1982a; Bradbury 1995; Butler 1988;

Elinder 1985; Fielding 1980; Jehu 1977; Leebeek 2001; Longstaffe

2000; Motavalli 1994; Nawaz 2002; Rodriguez 2001; Sukhai 1989

#; Tobias 2001; Wagner 1982; Wille 1986; Young 1972); the

remainder did not provide this information.

Risk of bias in included studies

Of the 56 included trials, nine reported concealment of alloca-

tion to groups which was probably adequate (e.g. by use of sealed

opaque envelopes or remote computer allocation, rated as A: Azrin

1974; Bradbury 1995; Leebeek 2001; Longstaffe 2000; Moffatt

1987; Motavalli 1994; Ng 2005; Scholander 1968; Sukhai 1989

#); 39 trials did not provide adequate detail for this to be assessed

(rated as B); and seven used methods where allocation definitely

was not adequately concealed (i.e. quasi-randomised such as alter-

nate numbers, rated as C: Butler 1990a; Butler 1990b; Kennedy

1968; Ronen 1992; Taylor 1975; Wagner 1985; Werry 1965). In

one further trial, although the initial randomisation was classed as

A and stratified by age and sex, there were differential dropouts

from the groups and they were non-systematically replaced result-

ing in unreliable groups (Turner 1970).

Crossover trials

There was one double-blind cross-over trial (Sukhai 1989 #). An

alarm in both arms of the trial was supplemented by desmopressin

or placebo for two weeks, crossing over to the alternative arm after a

two-week washout period. Follow-up information could therefore

not be given separately for each regimen.

Dropouts

Only three trials reported that there were no dropouts (Scholander

1968; Sukhai 1989 #; Wagner 1985). Where the drop-out rates

in treatment and comparison groups were similar and no reasons

were given, or where children randomised were found ineligible

or did not attend for initial monitoring, analyses were conducted

according to actual results reported, excluding drop-outs. There

were 28 such trials, in which dropouts did not seem to be affected

by group of allocation (Bennett 1985; Bollard 1981a; Butler 1988;

Butler 1990a; Butler 1990b; Elinder 1985; Faraj 1999; Fielding

1980; Forrester 1964; Fournier 1987; Geffken 1986a; Geffken

1986b; Houts 1986; Jehu 1977; Kolvin 1972; Lovibond 1964a;

Lynch 1984; Moffatt 1987; Netley 1984; Ng 2005; Rodriguez

2001; Ronen 1992; Wagner 1982; Werry 1965; Wright 1974). In

one other trial, the number of dropouts was unclear because each

was replaced with a subsequent child seen in the clinic (Taylor

1975) but as this did not seem to be affected by the intervention

allocated, the data have been used as reported.

However, where reasons for drop-out were reported as clearly re-

lated to the treatment group (e.g. unacceptability of the particular

treatment, adverse effects) they were included as failures. There

were three trials which reported such differential dropouts from

the groups, probably caused by adverse effects of the interven-

tions. In the first two, data were reported as if the dropouts were

failures (Bollard 1981b; McKendry 1975). In the other, children

were differentially withdrawn from treatment, making the groups

unreliable: data were not used from this study (Turner 1970).

Dropouts were usually due to: children not being sufficiently

enuretic at baseline assessment or found not to be eligible in other

ways for the trial; failure to attend for monitoring or follow up;

receiving the wrong intervention; non-compliance or difficulty

with using the equipment; family disruption; failure of the treat-

ment; and in the case of the alarms which delivered electric shocks,

the parents or the child being unwilling to experience the shocks

(Elinder 1985; Lovibond 1964a; McKendry 1975; Netley 1984).

Statistical reporting

Eighteen trials reported continuous data but failed to provide

measures of dispersion such as SDs (Azrin 1978; Baker 1969;

Bollard 1981a; Bollard 1981b; Bollard 1982a; Butler 1988; Butler

1990a; Butler 1990b; Danquah 1975; Fielding 1980; Finley 1973;

Fournier 1987; Jehu 1977; Kolvin 1972; Leebeek 2001; Wagner

1982; Wagner 1985; Wright 1974). These data were entered into

Other Data Tables.

Effects of interventions

1. Alarms compared with placebo / no treatment

control (Comparison 01, Other Data Tables 01)



Seventeen trials compared an alarm with a no-treatment control

group. The controls were:

• a no-treatment or waiting list control in 16 trials (Baker

1969; Bennett 1985; Bollard 1981a; Bollard 1981b; Hojsgaard

1979; Houts 1986; Jehu 1977; Lynch 1984; Moffatt 1987;

Nawaz 2002; Ronen 1992; Sacks 1974; Sloop 1973; Wagner

1982; Wagner 1985; Werry 1965); and

• one trial used a non-functioning device as a control

(Elinder 1985).

The types of alarms were:

• two trials used a delayed-alarm (Lynch 1984; Wagner

1985);

• one included an unsupervised alarm group (Bollard 1981a);

• two used an electric shock to the children’s skin, the Uristop

device (Elinder 1985; Hojsgaard 1979); and

• all remaining trials used a pad-and buzzer type of alarm to

wake the children when wetting occurred.

During treatment

Nine trials provided data about wet nights during treatment. On

average, there were over three fewer wet nights per week using the

standard alarm, compared to no-treatment controls (e.g. WMD -

3.34, 95% CI -4.14 to -2.55 in the four trials which reported SDs,

Comparison 01.01.01) (Bennett 1985; Lynch 1984; Nawaz 2002;

Ronen 1992); and in 6 of 6 trials where SDs were not reported

(Other Data Tables 01.02.01) (Baker 1969; Bollard 1981a; Bollard

1981b; Jehu 1977; Wagner 1982; Wagner 1985). In 13 trials,

the relative risk of failure was less in the alarm groups of all the

trials (107 of 316, 34% did not achieve 14 dry nights versus 250

of 260, 96% in no-treatment controls, RR 0.38, 95% CI 0.33

to 0.45, Comparison 01.03.01) (Bennett 1985; Bollard 1981a;

Bollard 1981b; Houts 1986; Jehu 1977; Lynch 1984; Moffatt

1987; Nawaz 2002; Ronen 1992; Sacks 1974; Sloop 1973; Wagner

1982; Wagner 1985; Werry 1965).

There was significant heterogeneity (P less than 0.00001). After

exclusion of two trials which involved children in residential homes

(Jehu 1977) or with learning disabilities (Sloop 1973) and a fur-

ther three trials which used quasi-randomised methods of alloca-

tion to groups (Ronen 1992; Wagner 1985; Werry 1965) the het-

erogeneity was reduced but still significant (P equals 0.013) while

the RR for failure remained similar in favour of alarm treatment

(RR 0.36, 95% CI 0.29 to 0.44). The remaining heterogeneity

may have been due to differences in types or effectiveness of the

alarms used (as the children in all the control groups had a similar

failure rate of over 90%) or differences between types of children

for example in baseline severity of wetting. It is more likely, how-

ever, that the heterogeneity is a statistical artefact caused by the

high proportion of children who failed, because the heterogeneity

disappears if the data are entered as cure rates instead of failure

rates.

Only three trials involved delayed or unsupervised alarms, but the

net effect was still generally in favour of the alarm group during

treatment (Comparisons 01.03.02, 01.03.03, Other Data Tables

01.02.02, 01.02.03) (Bollard 1981a; Lynch 1984; Wagner 1985).

After treatment stops

About half the children failed or relapsed after stopping standard

alarm treatment compared to nearly all after control interventions

(45 of 81 (55%) versus 80 of 81 (99%), RR 0.56, 95% CI 0.46

to 0.68, Comparison 01.04.01) (Bollard 1981a; Bollard 1981b;

Sloop 1973; Wagner 1982; Wagner 1985). There was no evidence

of heterogeneity amongst these five trials for this outcome. There

were no data for the number of wet nights after treatment stops.

Electric shock alarms

There was not enough evidence from two small trials to assess the

electric shock (Uristop) alarms (Comparison 01.03.04, Hojsgaard

1979; 01.03.05, Elinder 1985). It was reported that some children

were frightened of them, or their parents refused to let them be

used.

2. Comparisons between alarms (Comparison 02,

Other Data Tables 02)

Eleven trials compared different alarms or their use in different

circumstances. A large number of variations on standard alarm

treatment were tested, including:

• a body-worn alarm (Butler 1990a);

• intermittent alarm (Taylor 1975);

• time-delay before bell rings (Lynch 1984; Wagner 1985);

• alarm used without supervision (Bollard 1981a);

• loud versus quiet bells, with or without light (Finley 1973;

Finley 1977);

• an alarm which only wakes the parents (Finley 1973);

• a double (twin) alarm using both a bell and a buzzer

(Lovibond 1964a; Lovibond 1964c);

• an electric stimulation (shock) alarm (Crosby Dri-nite,

Lovibond 1964a); and

• a body-worn audio alarm versus a body-worn vibrating

alarm (Tobias 2001).

Immediate versus time delay alarm

In two small trials there were fewer wet nights when using an

alarm which woke the child immediately rather than after a time-

delay of 3 minutes (WMD -2.5, 95% CI -3.99 to -1.01, Compar-

ison 02.01.01, Lynch 1984; Other Data Tables 02.02.02, Wagner

1985) and differences in failure or relapse rates were consis-

tent with this but were not statistically significant (Comparisons

02.03.03, 02.04.03) (Lynch 1984; Wagner 1985).



Waking child versus waking parents

In one small trial, an alarm which woke the child directly was

more successful than one which only woke the parents (Compar-

isons 02.03.06, 02.03.07, 02.04.06, 02.04.07; Other Data Tables

02.02.05, 02.02.06) (Finley 1973).

Body-worn versus bed alarm

In another small trial, body-worn alarms appeared to be as effec-

tive as standard bed pad alarms (albeit with wide confidence inter-

vals) but children preferred the body-worn alarm (Comparisons

02.03.01, 02.04.01; Other Data Tables 02.02.01) (Butler 1990a).

Electric shock alarm

In one small trial, three children received corrosive skin burns and

two others discontinued treatment due to fear when using an alarm

which delivered an electric shock (Crosby Dri-nite, Lovibond

1964a). The alarm was therefore not used in subsequent trials.

Other alarms

There were no other clear differences between different types of

alarms or different ways of using them. However, some children

reported that the body-worn vibrating alarm was more uncom-

fortable than the audio alarm (Tobias 2001).

3. Alarms compared with behavioural interventions

(Comparison 03, Other Data Tables 03)

Eight trials compared alarms with a variety of simple or complex

behavioural interventions:

• star charts or rewards (Ronen 1992);

• star chart plus wakening (Baker 1969);

• wakening or lifting (Fournier 1987; Lovibond 1964b);

• retention control training and stop-start training (pelvic

floor muscle training) (Bennett 1985); and

• Dry Bed Training (complex intervention without an alarm)

(Azrin 1978; Bollard 1981b; Caceres 1982).

Simple behavioural interventions

Alarms were better than stop-start training in terms of wet nights

per week both during (WMD -2.25, 95% CI -4.2 to -0.3) and after

(WMD -2.6, 95% CI -4.53 to -0.67) treatment in one small trial

(Comparisons 03.01.02, 03.04.01) (Bennett 1985). However, the

chance of cure was not significantly higher (Comparison 03.03.02)

although in the same direction.

There were no significant differences between alarms and other

simple behavioural methods such as lifting, wakening or rewards

in four other trials (Baker 1969; Fournier 1987; Lovibond 1964b;

Ronen 1992), although all trials tended to favour alarms in respect

of mean wet nights (Comparison 03.01.01, Other Data Tables

03.02.01, 03.02.02, 03.02.03).

Complex behavioural interventions

During treatment, there was no clear difference in wet nights

between alarm and dry bed training in three trials (without

an alarm) (Comparison 03.03.03; Other Data Tables 03.02.03)

(Azrin 1978; Bollard 1981b; Caceres 1982), but there was sig-

nificant heterogeneity. In the Azrin trial, children only received

treatment for two weeks before being switched to the other arm,

which may not have been long enough for the alarm to work

(Azrin 1978). Excluding this trial, the heterogeneity was no longer

significant and the RR for failing to achieve 14 dry nights was

0.22, 95% CI 0.09 to 0.53 (Bollard 1981b; Caceres 1982). In the

one small trial which provided data after the trial stopped, there

was less chance of failure or relapse after alarm treatment alone

than after dry bed training alone (RR 0.59, 95% CI 0.37 to 0.95,

Comparison 03.05.03) (Bollard 1981b).

4. Alarms compared with alarm programmes

augmented by behavioural interventions

(Comparison 04, Other Data Tables 04)

Sixteen trials compared alarms alone with alarm programmes aug-

mented by behavioural interventions:

• supplementation of the alarm by supervision (Bollard

1981a);

• alarm plus retention control training (Bollard 1982a;

Fielding 1980; Geffken 1986a; Geffken 1986b; Houts 1986);

• alarm plus dry bed training (Azrin 1974; Bennett 1985;

Bollard 1981b; Bollard 1982a; Butler 1988; Butler 1990b;

Nawaz 2002);

• alarm plus waking (Bollard 1982a);

• alarm plus rewards with and without penalties (van Londen

1993);

• alarm plus overlearning (Houts 1986; Taylor 1975; Young

1972); and

• alarm plus positive practice with cleanliness training

(Bollard 1982a).

Supplementing alarms with retention control training

Although alarms alone were better than alarms plus retention con-

trol training in five trials in terms of failure rates during treat-

ment (RR 0.37, 95% CI 0.18 to 0.76, Comparison 04.03.02)

(Bollard 1982a; Fielding 1980; Geffken 1986a; Geffken 1986b;

Houts 1986), this was not reflected in terms of wet nights dur-

ing treatment (Comparison 04.01.01) (Geffken 1986a; Geffken

1986b) or in failure or relapse rates after the end of treatment

(RR 1.12, 95% CI 0.77 to 1.64, Comparison 04.04.02) (Fielding

1980; Geffken 1986a; Geffken 1986b; Houts 1986). However,

the trials were all small.



Supplementing alarms with overlearning

Although the results during treatment were similar for alarms

compared with alarms plus overlearning (Comparisons 04.03.04,

04.03.05) there may be less relapse after treatment stops if over-

learning is used after successful alarm treatment (33 of 67 (49%)

failed or relapsed after alarms alone versus 19 of 77 (25%)

with overlearning, RR 1.92, 95% CI 1.27 to 2.92, Comparison

04.04.04) (Taylor 1975; Young 1972).

Supplementing alarms with dry bed training

In the five trials which compared an alarm alone with an alarm

supplemented by dry bed training (Bennett 1985; Bollard 1981b;

Butler 1988; Butler 1990b; Nawaz 2002) the trend in favour

of supplementation did not reach statistical significance (Com-

parisons 04.01.02, 04.03.06, 04.04.04; and Other Data Tables

04.02.03) and there was significant heterogeneity in the three

Comparisons. This heterogeneity could have been due to the in-

clusion of one trial (Butler 1990b) which used different types of

alarms in the two arms (bed alarm plus DBT in one versus body-

worn (pants) alarm in the other). All the children included in this

trial had already failed using a standard bed alarm. Removal of this

trial reduced or removed the heterogeneity: the failure or relapse

rate was reduced in the group supplemented with dry bed training

(20/32, 63% relapsing with alarm alone versus only 20 of 72, 27%

when supplemented with dry bed training: RR 2.0, 95% CI 1.25

to 3.20, Comparison 04.04.07) (Bollard 1981b; Nawaz 2002).

Supplementing alarms with rewards and penalties

In one trial, adding rewards for dry beds or correct behaviour

to alarm treatment was associated with lower failure rates during

treatment (Comparison 04.03.08) but using penalties for wet beds

was less effective or counterproductive after treatment had finished

(e.g. failure or relapse rate 10 of 36 (28%) after alarms alone versus

21of 39 (54%) when supplemented by penalties, RR 0.52, 95%

CI 0.28 to 0.94, Comparison 04.04.09 and RR 0.54, 95% CI

0.30 to 0.96, Comparison 04.04.10) (van Londen 1993).

Other methods of augmentation

In general, participants using alarms alone were as likely to attain

14 consecutive dry nights as those whose alarms were augmented

with other strategies, but the confidence intervals were all wide.

The pattern of results remained essentially the same when subse-

quent relapse rates were also taken into account.

5. Alarms compared with drugs (Comparison 05,

Other Data Tables 05)

Twenty trials included a comparison of alarms with drugs either

alone or in combination. These included:

• placebo (Fournier 1987; Kolvin 1972; Longstaffe 2000;

Wright 1974);

• desmopressin (Faraj 1999; Longstaffe 2000; Ng 2005;

Wille 1986);

• alarm supplemented by desmopressin (Bradbury 1995;

Gibb 2004; Leebeek 2001; Ng 2005; Sukhai 1989 #; Rodriguez

2001);

• imipramine and other tricyclics (Danquah 1975; Fournier

1987; Kolvin 1972; McKendry 1975; Motavalli 1994; Netley

1984; Wagner 1982);

• alarm supplemented by a tricyclic (Fournier 1987;

Scholander 1968); and

• other drugs (Forrester 1964; Kennedy 1968; Wright 1974).

Alarm versus placebo alone

Alarms were better than placebo drug treatment in terms of

fewer wet nights during and after treatment (Other Data Tables

05.02.01, 05.04.01) (Fournier 1987; Kolvin 1972; Wright 1974),

and a lower failure rate during treatment (RR 0.68, 95% CI 0.48

to 0.97, Comparison 05.03.01) (Longstaffe 2000). Follow-up data

after stopping treatment were not available.

Alarm versus desmopressin alone

In the first week of treatment, children had fewer wet nights dur-

ing desmopressin treatment (WMD 2.1, 95% CI 0.99 to 3.21,

Comparison 05.01.03) (Wille 1986). Towards the end of treat-

ment, they had fewer wet nights on alarms in three trials but

this did not reach statistical significance and there was hetero-

geneity (WMD -0.41 wet nights fewer with alarms, 95% CI -

1.20 to 0.38, random effects used, Comparison 05.01.04) (Ng

2005; Wille 1986); Other Data Tables 05.02.02, (Faraj 1999)).

Although there was a lower failure rate during alarm treatment in

four trials (RR 0.85, 95% CI 0.53 to 1.37, Comparison 05.03.02)

(Faraj 1999; Longstaffe 2000; Ng 2005; Wille 1986), this did

not reach statistical significance and there was significant hetero-

geneity (therefore random effects used). Two small trials provided

follow-up data: although fewer children failed or relapsed after

alarm treatment stopped (29 of 57 (51%) versus 46 of 62 (74%)

after desmopressin, this did not reach statistical significance and

random effects were used due to heterogeneity (RR 0.53, 95%

CI 0.14 to 2.06, Comparison 05.05.01) (Ng 2005; Wille 1986):

some of the heterogeneity might be explained because the defini-

tion of cure was less strict than 14 consecutive dry nights in one

of the trials (Wille 1986). There were, however, fewer wet nights

after alarm treatment stopped in both trials (WMD -1.59, 95%

CI -2.86 to -0.32 using random effects, Comparison 05.06.01)

(Ng 2005; Wille 1986).

Alarm versus alarm combined with desmopressin treatment



Data about wet nights during treatment were conflicting: children

had fewer wet nights during combination treatment in three par-

allel group trials (WMD 0.77, 95% CI 0.44 to 1.09, Comparison

05.01.05) (Bradbury 1995; Gibb 2004; Ng 2005) but more wet

nights in another which failed to report SDs (Other Data Tables

05.02.03) (Leebeek 2001). Failure rates during treatment were

not significantly different and there was heterogeneity (RR 1.32,

95% CI 0.80 to 2.16 using random effects, Comparison 05.03.03)

(Bradbury 1995; Gibb 2004; Ng 2005; Rodriguez 2001). Subse-

quent failure or relapse rates were similar in four trials (RR 1.10,

95% CI 0.92 to 1.31, Comparison 05.05.02) (Bradbury 1995;

Gibb 2004; Leebeek 2001; Ng 2005) but the confidence intervals

were wide. The number of wet nights at follow up was higher in

the combined treatment group in one trial without SDs (Other

Data Tables 05.04.03) (Leebeek 2001) and similar in one new trial

(WMD -0.1, 95% CI -1.55 to 1.35, Comparison 05.06.02) (Ng

2005).

Alarm versus tricyclics alone

Although there were fewer wet nights during alarm treatment com-

pared with imipramine, amitriptyline or clomipramine in four tri-

als arms out of five (Comparison 05.01.01, 05.01.02, Other Data

Tables 05.02.04) (Fournier 1987; Kolvin 1972; Motavalli 1994;

Wagner 1982); this did not reach statistical significance in any of

them. Although fewer children failed during alarm treatment in

three trials involving imipramine (61of 105 (58%) versus 82 of

103 (80%), RR for failure 0.59, 95% CI 0.32 to 1.09, Compar-

ison 05.03.04) (McKendry 1975; Netley 1984; Wagner 1982),

these differences were not significant as a random effects model

was used due to heterogeneity. After treatment stopped, fewer chil-

dren failed or relapsed after alarms in one small trial (RR 0.58,

95% CI 0.36 to 0.94, Comparison 05.05.03) (Wagner 1982) and

fewer had wet nights at follow up in another (Other Data Tables

05.04.02) (Kolvin 1972).

Alarm versus alarm combined with tricyclics

There was no clear evidence that supplementing alarm treatment

with a tricyclic was better than the alarm treatment alone (Com-

parisons 05.03.06, 05.05.04 (Scholander 1968), Other Data Ta-

ble 05.02.05 (Fournier 1987)) but each comparison was addressed

in single small trials.

Alarm versus drugs other than desmopressin or tricyclics

There was too little information about a mixture of drugs (am-

phetamine, ephedrine and atropine) or methedrine compared with

alarms (Other Data Table 05.02.06, (Wright 1974); Compar-

ison 05.03.07) (Kennedy 1968)) although amphetamine alone

was worse than alarms in one small trial (Comparison 05.03.08)

(Forrester 1964).

Standard alarm versus electric shock alarms

In two trials (involving imipramine in other groups), children were

frightened of receiving shocks from a body-worn alarm which de-

livered skin shocks (the Mozes detector), and in one of them, some

reported burns or ulceration (McKendry 1975; Netley 1984).

Some parents refused to let their children use these alarms.

6. Alarms compared with other / miscellaneous

treatments (Comparison 06, Other Data Tables 06)

Five trials compared alarms with interventions other than be-

havioural or drugs:

• cognitive therapy or psychotherapy (Ronen 1992; Sacks

1974; Werry 1965);

• ritual shaming (Danquah 1975); and

• restricted diet (McKendry 1975).

During treatment

Although the number of wet nights during treatment was sim-

ilar (Comparison 06.01) (Ronen 1992) more children achieved

14 dry nights during alarm treatment compared with cognitive or

psychotherapy (RR for failure 0.68, 95% CI 0.52 to 0.90, Com-

parison 06.03.02) (Ronen 1992; Sacks 1974; Werry 1965) and re-

stricted diet (Comparison 06.03.01) (McKendry 1975). There was

statistically significant heterogeneity (P equals 0.0007). Amongst

the three trials comparing alarms with cognitive or psychotherapy,

one used a disproportionate method of allocation of children to

groups, resulting in very small control and psychotherapy groups;

there were also differences in baseline characteristics amongst the

controls (Sacks 1974). Excluding this trial removed the statistical

heterogeneity but also the significant difference in the chance of

failure (RR 0.93, 95% CI 0.67 to 1.30): however, both remain-

ing trials used quasi-randomised methods of allocation to groups

(Ronen 1992; Werry 1965).

After treatment stops

Follow up data after the end of treatment were only available for

two small trials: the RR for failure or relapse was higher in the alarm

group than after cognitive therapy (9 of 15 (60%) versus 3 of 18

(17%), RR 3.60, 95% CI 1.18 to 10.95, Comparison 06.04.01) (

Ronen 1992). Children had fewer wet nights after alarm treatment

than after ritual shaming, but SDs were not provided (Other Data

Table 06.05.01, Danquah 1975).

Adverse events and side effects

Thirteen trials of conventional pad-and-buzzer alarms triggered

by wetting included information about adverse effects (Baker

1969; Fournier 1987; Gibb 2004; Jehu 1977; Lovibond 1964a;

McKendry 1975; Moffatt 1987; Netley 1984; Scholander 1968;



Tobias 2001; Turner 1970; Wagner 1985; Wille 1986). Only one

trial stated explicitly that there were no adverse events (Leebeek

2001). The remainder did not mention this outcome. The adverse

events or side effects included: alarm failure; false alarms; fright;

failing to wake the child; and waking others causing family disrup-

tion. A vibrating alarm was reported to be uncomfortable (Tobias

2001), and in a drug trial one headache and one nosebleed were

reported (Gibb 2004). In two trials, non-compliance or dropout

was attributed to the equipment being too difficult or complicated

to use (Moffatt 1987; Turner 1970).

It was quite clear that the alarms which delivered electric shocks

to the children’s skin had unacceptable side effects (the Mozes de-

tector, McKendry 1975; Netley 1984; the Uristop (Elinder 1985;

Hojsgaard 1979) and the Crosby Dri-Nite (Lovibond 1964a). Not

only were children (especially the younger ones) frightened of

them (Netley 1984), there were incidents of skin burns and other

damage (Lovibond 1964a; McKendry 1975).

D I S C U S S I O N

This review updates two previous versions (Lister-Sharp 1997;

Glazener 2001). In the previous update, 20 new trials were added,

as were 12 trials which were previously included only in sensitivity

analyses. The 12 previously excluded trials had failed to report

on either baseline wetting or exclusion of organic causes, but it

was decided to include them in this update as they were otherwise

properly randomised controlled trials. In the current update, three

new trials were added.

Data for several important outcomes were only reported in sin-

gle small trials (such as failure and relapse rates following alarm

treatment compared to desmopressin treatment, Wille 1986). The

sample sizes were generally small. The lack of a sufficiently large

sample can result in failure to detect a real treatment difference

(because the confidence intervals are wide), or conversely, finding

an exaggerated difference to be statistically significant by chance.

Quality of randomisation and follow-up data

Amongst the 53 included trials, the method of concealment of

allocation to groups was only of good methodological quality in

eight trials. Seven others used a suboptimal (quasi-randomised)

method of randomisation. Only 26 of the 53 included trials pro-

vided longer term results after treatment was finished. This is a

serious shortcoming of the research, as continued effectiveness is

the main aim of treatment. However, in some cases, it reflected

the clinical situation in which families whose children continue to

wet the bed ask for alternative treatment.

Differential dropout

In three trials, dropout rates were different from different trial

arms. In two trials, drop-out was related to unacceptability of treat-

ment (Bollard 1981b; McKendry 1975). In these trials, dropouts

have been counted as failures. In a third trial, trial data were not

used in analyses because children were switched between groups,

making the data unreliable (Turner 1970). In the remaining trials,

dropout rates were evenly distributed amongst the trial arms and

results excluded dropouts. The meta-analyses also excluded drop-

outs in these cases.

Organic causes and daytime wetting

It is likely that the underlying pathologies of night-only

(monosymptomatic) bedwetting and mixed night and day (diur-

nal) wetting differ. Those with diurnal wetting are more likely to

have an organic cause for their problem, and may be less likely

to respond to treatment unless the underlying disease is treated

(Jarvelin 1989; Jarvelin 1990). Although the focus of the review

was on monosymptomatic nocturnal enuresis, only 16 trials specif-

ically excluded children with daytime wetting and six included at

least some such children (the remainder provided no information

about this issue). However, of the six, four specifically excluded

children with organic causes. In total, 48 trials specifically excluded

children with known organic causes for their enuresis. Of the seven

trials which did not specify whether they excluded children with

organic causes or not, only two trials included some children with

daytime wetting. Therefore the majority of included trials (51)

were likely to be amongst children without a recognised physical

cause for their problem. To have included only the 16 trials which

explicitly excluded all children with daytime wetting would have

limited the review. The results should be interpreted with this in

mind.

Settings for treatment

Most of the included trials have recruited children from enuresis

clinics or are hospital based. Participating families may be espe-

cially motivated to tackle the bed wetting. In addition, strict inclu-

sion / exclusion criteria have been imposed in many of the trials.

Consequently, the children involved are not necessarily represen-

tative of the wider population of those who wet the bed. Only

three small trials included children who were learning disabled or

from residential homes. The two larger of these trials favoured

alarm treatment (Jehu 1977; Sloop 1973) but the data were too

few to be generalisable.

Effectiveness of alarms

Alarms versus no treatment



Alarm treatment was clearly better than no treatment or waiting

list control interventions, both during treatment and in terms of

continuing success rates after treatment was finished. About half

the children fail or relapse after alarms compared with almost all

who have a control treatment. Blinding of alarm treatment is dif-

ficult even if non-functioning equipment is used (as the patient

will be aware that the alarm does not go off ), and trials of conven-

tional pad-and-buzzer alarms compared with sham alarms were

not found. One trial of an electric shock device did use a sham

alarm but the active treatment was not acceptable.

Different types of alarms

There was some evidence that an immediate alarm (compared to

a delayed alarm or one which woke the parents rather than the

child) was better. In another trial, children preferred a body-worn

alarm to a bed pad, and an audio body-worn alarm to a vibrating

body-worn alarm, but in general there was insufficient evidence

to suggest that one type of alarm was better than another.

Alarms versus behavioural interventions

There was insufficient evidence to demonstrate a difference be-

tween alarms and simple behavioural interventions such as lifting,

wakening or reward systems, because each intervention was ad-

dressed only by single small trials. Alarms resulted in fewer wet

nights than stop-start training (teaching children to contract their

pelvic floor muscles) but the single trial was too small to show

reliably whether there was a difference in cure rates. Children were

less likely to fail or relapse after alarm treatment alone than dry

bed training alone in another small trial. There was some evidence

that rewards increased the effectiveness of alarms whereas penalties

after bed wetting appeared to reduce the likelihood of success.

Supplementing alarms with behavioural interventions

Although 16 trials addressed the issue of supplementing alarm

treatment by reinforcing it with behavioural interventions, there

was not much evidence to say whether or not this improved per-

formance of the alarm: the trials were all small, many did not

report SDs, and the confidence intervals, where available, were

wide. However, two small trials suggested that overlearning after

successful alarm treatment halved the relapse rate from 49% to

25% (Taylor 1975; Young 1965). Similarly, in two other trials,

supplementing alarms with dry bed training reduced the relapse

rate from 63% to 27% (Bollard 1981b; Nawaz 2002). Finally, one

small trial suggested that giving children penalties for wet beds

was unhelpful (van Londen 1993). These findings need to be con-

firmed in further research as the trials were small and some had

methodological flaws. Retention control training (gradually trying

to increase bladder capacity by teaching children to ’hold on’) in

addition to an alarm was detrimental during treatment, although

it was not associated with significant differences in relapse rates

after treatment stopped.

Alarms versus drugs

Limited evidence suggested that alarms were better than placebo

drug treatment, but direct comparisons with desmopressin or tri-

cyclics alone were conflicting, in contrast with the findings of an

earlier version of this review (Glazener 2005a). These findings were

based on single or small trials, and need to be confirmed in future

research. However, two larger reviews (of desmopressin Glazener

2002) and tricyclics (Glazener 2003a) suggest that drug treatment

alone, while effective for some children during treatment, is un-

likely to be followed by sustained cure as almost all the children

relapsed.

Supplementing alarms with drugs

There is a move towards combining alarms with drug interven-

tions (Howe 1992). The rationale is that the rapid onset of action

of drugs is then combined with the more gradual treatment effect

of alarms (Sukhai 1989 #). Low doses of desmopressin as an ad-

junct to alarm treatment may also be used to ensure that the child

only wets the bed once each night to minimise changes of bedding

(Djurhuus 1992). There was insufficient evidence to support this:

while supplementing alarms with desmopressin did decrease the

initial number of wet nights in four trials, success rates while on

treatment or afterwards were not significantly different compared

to an alarm alone. There was insufficient information about sup-

plementing alarms with tricyclics.

Alarms versus other treatments

Limited evidence suggested that alarms were generally better than

any of a variety of other classes of interventions while on treatment,

but follow up data were only available from two small trials.

Acceptability of alarms

High dropout rates in some of the trials suggest that there were

problems with compliance, often reflecting the unacceptability

of the treatment. Potential difficulties, such as the time needed

to attain success and the initial disruption to the family, need to

be discussed with families before embarking on alarm treatment.

Some child or family variables have been shown to predict dropout,

such as parental intolerance, behavioural problems or the child’s

negative self image (Wagner 1982; Butler 1988; Wagner 1988;

Butler 1994). These may be useful for identifying which treatment

is most likely to succeed, or where the chances of success may be

increased by giving the family extra attention.



Adverse events

Adverse events with standard pad-and-bell alarms which woke the

children on wetting were limited to minor inconvenience due to

alarm malfunction or disturbance to the family. In contrast, side

effects with drugs may have more serious implications (Glazener

2002; Glazener 2003a). For example, tricyclics may have serious

side-effects such as arrhythmias and heart block, convulsions, and

hepatic and haematological reactions. These may present a partic-

ular risk of overdose to the children treated or other family mem-

bers (Fitzwater 1992; Parkin 1972; Rushton 1993).

However, the alarms which delivered electric shocks to the chil-

dren’s skin on wetting were clearly unacceptable, in terms of fright-

ening the children and causing burns and ulceration.

Costs

In the UK, 16 weeks of drug treatment (the usual time allowed

for fourteen consecutive dry nights to be attained using an alarm,

Butler 1991) would cost (BNF 2002):

• £78 for desmopressin nasal spray (20 µg per night) or £116

for desmopressin tablets (200 µg);

• £4 for imipramine hydrochloride (25 mg tablet per night)

or £14 for imipramine syrup (25 mg); and

• enuresis alarms (including batteries & sensor) typically cost

£33.60, although alarms but not sensors (£12) may be re-used

several times.

This information relates only to some of the direct costs to the

health service. Although treatment with tricyclic or related drugs

is considerably less expensive than alarms or desmopressin, this

does not take into account the administrative or the human costs

involved in using alarms. Alarm systems may not be returned to

clinics and have to be followed up. Alarm treatment is accompa-

nied by broken nights for various family members until success

is attained. Staff must be trained to teach the children and their

parents how to use the alarms (particularly that the child must be

fully wakened) and ensure that the equipment is working. Staff

also need time to teach the parents and provide support during

treatment.

The Guidelines on Minimum Standards of Practice (Morgan

1993) suggest that follow-up supervisory contacts should occur

at least every three weeks, with management reviewed at least

monthly. Against this must be set the possible reduced risk of re-

lapse after stopping alarms compared with after stopping treat-

ment with desmopressin, tricyclics or related drugs, and the po-

tential for adverse events with tricyclics.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

Using an audio alarm system on its own to condition children

to wake before they wet the bed appears effective after treatment

stops for about half of children with nocturnal enuresis. Supple-

menting alarm treatment with overlearning (giving children extra

fluids at bedtime after successfully becoming dry using an alarm),

dry bed training and avoiding penalties may reduce the relapse

rate. Although the evidence suggests that desmopressin has a more

immediate effect than alarms, alarms seem better than desmo-

pressin or tricyclics in reducing the number of wet nights by the

end of a course of treatment. There is no reliable evidence that

the drugs are effective after treatment has stopped (Glazener 2002;

Glazener 2003a) whereas half the children remain dry after alarm

treatments.

Although the cost of alarm treatment is intermediate between

desmopressin and tricyclics, greater motivation and time are

needed by families until alarm treatment is successful. However,

the finding that effects are better sustained after alarm treatment,

and the risks of side effects associated with drugs, suggest that

alarms may be preferable to the pharmacological options.

The limited evidence suggested that alarms on their own were as

good as or better than most other behavioural or other classes of

interventions.

Implications for research

Although treatment with alarms, desmopressin and tricyclics have

each been shown to be effective in a number of trials, there are few

direct comparisons between them, or between different types of

alarms (e.g. loudness, type of stimulus). These need further inves-

tigation. Current evidence on which to judge behavioural or other

interventions is limited, and further trials of these compared with

alarms, desmopressin or tricyclics are needed. Such trials should

allow comparison in different populations and for different pur-

poses (such as in primary care, or as a short-term measure to cover

nights away from home), in order to inform choice of treatment.

They should include formal testing to identify pre-treatment fac-

tors which might modify or determine treatment effects. Impor-

tant factors include age, presence of organic causes or daytime

wetting and family circumstances.

Future trials should focus on children without organic causes of

bedwetting, and should include adequate assessment of baseline

levels of wetting. The difficulty in comparing interventions is ex-

acerbated by the lack of uniformity in outcome measures, which

should include: the number of wet nights during treatment and af-

ter the end of treatment; the number of children failing to achieve

14 consecutive dry nights; adverse events; acceptability of treat-

ment; compliance; and especially relapse rates after treatment has

stopped (expressed as a composite outcome of failure to achieve

14 dry nights and subsequent relapse). It is crucial to be able to



assess the success rates of different treatments at least three months

after they have finished.

Children with daytime enuresis are more likely to have specific

pathology such as bladder dysfunction or urinary tract infections.

Alternative managements for this condition need to be assessed in

a separate Cochrane Review.

A C K N O W L E D G E M E N T S

This review was originally written for the National Health Service

Centre for Reviews & Dissemination (CRD), University of York,

UK, by Deborah Lister-Sharp, Susan O’Meara, Matthew Bradley

and Trevor A Sheldon. It was published as: A Systematic Review of

the Effectiveness of Interventions for Managing Childhood Noc-

turnal Enuresis, CRD Report 11, NHS Centre for Reviews and

Dissemination, University of York (Lister-Sharp 1997). We were

especially grateful to Deborah Lister-Sharp for transfer of data,

trials and expertise, and were sad to learn of her death.

The CRD reviewers obtained information from a variety of

sources, including organisations, manufacturers and individuals.

These are listed in the original report, and we acknowledge their

contribution to this review.

We are grateful to Penny Dobson (Enuresis Resource and Infor-

mation Centre, ERIC, Bristol, UK) for help and encouragement,

and also facilitating consumer reviewing. We would like to thank

the external peer reviewers. We would also like to thank the Con-

sumer Network at the Australasian Cochrane Centre for help with

the synopsis.

R E F E R E N C E S

References to studies included in this review

Azrin 1974 {published data only}

Azrin NH, Sneed TJ, Foxx RM. Dry-bed training: rapid

elimination of childhood enuresis. Behaviour Research &

Therapy 1974;12(3):147–56. [MEDLINE: 75054129]


Azrin NH, Thienes PM. Rapid elimination of enuresis

by intensive learning without a conditioning apparatus.

Behaviour Therapy 1978;9:342–54.

Baker 1969 {published data only}

Baker BL. Symptom treatment and symptom substitution

in enuresis. Journal of Abnormal Psychology 1969;74(1):

42–9. [MEDLINE: 69166759]

Bennett 1985 {published data only}

Bennett GA, Walkden VJ, Curtis RH, Burns LE, Rees J,

Gosling JA, et al.Pad-and-buzzer training, dry-bed training,

and stop-start training in the treatment of primary nocturnal

enuresis. Behavioural Psychotherapist 1985;13:309–19.

Bollard 1981a {published data only}

Bollard J. A 2-year follow-up of bedwetters treated by dry-

bed training and standard conditioning. Behaviour Research

& Therapy 1982;20(6):571–80. [MEDLINE: 83126391]∗ Bollard J, Nettelbeck T. A comparison of dry-bed training

and standard urine-alarm conditioning treatment of

childhood bedwetting. Behaviour Research & Therapy 1981;

19(3):215–26. [MEDLINE: 82045721]

Bollard 1981b {published data only}

Bollard J. A 2-year follow-up of bedwetters treated by dry-

bed training and standard conditioning. Behaviour Research

& Therapy 1982;20(6):571–80. [MEDLINE: 83126391]∗ Bollard J, Nettelbeck T. A comparison of dry-bed training

and standard urine-alarm conditioning treatment of

childhood bedwetting. Behaviour Research & Therapy 1981;

19(3):215–26. [MEDLINE: 82045721]

Bollard 1982a {published data only}

Bollard J, Nettelbeck T. A component analysis of dry-bed

training for treatment for bedwetting. Behaviour Research &

Therapy 1982;20(4):383–90. [MEDLINE: 83022183]

Bradbury 1995 {published data only}

Bradbury M. Combination therapy for nocturnal enuresis

with desmopressin and an alarm device. Scandinavian

Journal of Urology & Nephrology 1997;Supplementum.

183:61–3. [MEDLINE: 97308385]∗ Bradbury MG, Meadow SR. Combined treatment with

enuresis alarm and desmopressin for nocturnal enuresis.

Acta Paediatrica 1995;84(9):1014–8. [MEDLINE:

96112940]

Butler 1988 {published data only}

Butler RJ, Brewin CR, Forsythe WI. A comparison of two

approaches to the treatment of nocturnal enuresis and the

prediction of effectiveness using pre-treatment variables.

Journal of Child Psychology & Psychiatry & Allied Disciplines

1988;29(4):501–9. [MEDLINE: 89109292]

Butler 1990a {published data only}

Butler RJ, Forsythe WI, Robertson J. The body-worn alarm

in the treatment of childhood enuresis. British Journal

of Clinical Practice 1990;44(6):237–41. [MEDLINE:

91001782]

Butler 1990b {published data only}

Butler RJ, Forsythe WI, Robertson J. The body-worn alarm

in the treatment of childhood enuresis. British Journal

of Clinical Practice 1990;44(6):237–41. [MEDLINE:

91001782]



Caceres 1982 {published data only}∗ Caceres J. Comparative efficacy between two methods for

the treatment of enuresis. Revista de Psicologia General y

Aplicada 1980;35(4):597–616.

Caceres J. Enuresis: Cortical control or social reinforcement?

. Behaviour Therapist 1982;5(2):65–7.

Caceres J. Enuresis: Cortical control or social reinforcement?

. Revista de Psicologia General y Aplicada 1979;34(161):

1067.

Danquah 1975 {published data only}

Danquah SA. Comparative treatment of nocturnal enuresis

among Ghanaian school children. Psychopathologie Africaine

1975;11(3):363–73.

Elinder 1985 {published data only}

Elinder G, Soback S. Effect of Uristop on primary

nocturnal enuresis. A prospective randomized double-blind

study. Acta Paediatrica Scandinavica 1985;74(4):574–8.

[MEDLINE: 85275411]

Faraj 1999 {published data only}

Faraj G, Cochat P, Cavailles ML, Chevallier C. [Treatment

of isolated nocturnal enuresis: alarm or desmopressin?

]. [French]. Archives de Pediatrie 1999;6(3):271–74.

[MEDLINE: 99207616]

Fielding 1980 {published data only}

Fielding D. The response of day and night wetting children

and children who wet only at night to retention control

training and the enuresis alarm. Behaviour Research &

Therapy 1980;18(4):305–17. [MEDLINE: 81062334]

Finley 1973 {published data only}

Finley WW, Besserman RL, Bennett LF, Clapp RK, Finley

PM. The effect of continuous, intermittent, and “placebo”

reinforcement on the effectiveness of the conditioning

treatment for enuresis nocturna. Behaviour Research &

Therapy 1973;11(3):289–97. [MEDLINE: 73243969]


Finley WW, Wansley RA. Auditory intensity as a variable in

the conditioning treatment of enuresis nocturna. Behaviour

Research & Therapy 1977;15(2):181–5. [MEDLINE:

77201389]

Forrester 1964 {published data only}

Forrester RM, Stein Z, Susser MW. A trial of conditioning

therapy in nocturnal enuresis. Developmental Medicine &

Child Neurology 1964;6:158–66.

Fournier 1987 {published data only}

Fournier JP, Garfinkel BD, Bond A, Beauchesne H,

Shapiro SK. Pharmacological and behavioral management

of enuresis. Journal of the American Academy of Child &

Adolescent Psychiatry 1987;26(6):849–53. [MEDLINE:

88115081]

Geffken 1986a {published data only}

Geffken G, Johnson SB, Walker D. Behavioral interventions

for childhood nocturnal enuresis: the differential effect of

bladder capacity on treatment progress and outcome. Health

Psychology 1986;5(3):261–72. [MEDLINE: 86300621]

Geffken 1986b {published data only}

Geffken G, Johnson SB, Walker D. Behavioral interventions

for childhood nocturnal enuresis: the differential effect of

bladder capacity on treatment progress and outcome. Health

Psychology 1986;5(3):261–72. [MEDLINE: 86300621]

Gibb 2004 {published data only}

Gibb S, Nolan T, South M, Noad L, Bates G, Vidmar S.

Evidence against a synergistic effect of desmopressin with

conditioning in the treatment of nocturnal enuresis. Journal

of Pediatrics 2004;144(3):351–7.

Hojsgaard 1979 {published data only}

Hojsgaard A, Genster H. Effect of Uristop in children with

enuresis. A prospective randomized clinical trial. [Danish].

Ugeskrift for Laeger 1979;141(10):647–8. [MEDLINE:

79139924]

Houts 1986 {published data only}

Houts AC, Peterson JK, Whelan JP. Prevention of relapse

in full-spectrum home training for primary enuresis: A

components analysis. Behaviour Therapy 1986;17:462–9.

Jehu 1977 {published data only}

Jehu D, Morgan RT, Turner RK, Jones A. A controlled trial

of the treatment of nocturnal enuresis in residential homes

for children. Behaviour Research & Therapy 1977;15(1):

1–16. [MEDLINE: 77111772]

Kennedy 1968 {published data only}

Kennedy WA, Sloop EW. Methedrine as an adjunct to

conditioning treatment of nocturnal enuresis in normal

and institutionalized retarded subjects. Psychological Reports

1968;22:997–1000. [MEDLINE: 68274635]

Kolvin 1972 {published data only}

Kolvin I, Taunch J, Currah J, Garside RF, Nolan J, Shaw

WB. Enuresis: a descriptive analysis and a controlled trial.

Developmental Medicine & Child Neurology 1972;14(6):

715–26. [MEDLINE: 73066897]

Leebeek 2001 {published data only}

Leebeek-Groenewegen ANJA, Blom J, Sukhai R, van der

Heijden B. Efficacy of desmopressin combined with alarm

therapy for monosymptomatic nocturnal enuresis. Journal

of Urology 2001;166(6):2456–8. [MEDLINE: 21553449]

Longstaffe 2000 {published data only}

Longstaffe S, Moffatt ME, Whalen JC. Behavioral and self-

concept changes after six months of enuresis treatment: a

randomized, controlled trial. Pediatrics 2000;105(4:Pt 2):

935–40. [MEDLINE: 20209556]

Lovibond 1964a {published data only}

Lovibond SH. Field experiment I: Experimental comparison

of twin signal, Crosby and Mowrer instruments.

Conditioning and Enuresis. New York: MacMillan

(Pergamon Press), 1964:94–101.

Lovibond 1964b {published data only}

Lovibond SH. Field experiments on the reduction of

the relapse rate. Conditioning and Enuresis. New York:

MacMillan (Pergamon Press), 1964:121–31.



Lovibond 1964c {published data only}




Lynch 1984 {published data only}

Lynch NT, Grunert BK, Vasudevan SV, Severson RA.

Enuresis: comparison of two treatments. Archives of

Physical Medicine & Rehabilitation 1984;65(2):98–100.

[MEDLINE: 84127291]

McKendry 1975 {published data only}

McKendry JB, Stewart DA, Khanna F, Netley C. Primary

enuresis: relative success of three methods of treatment.

Canadian Medical Association Journal 1975;113(10):953–5.

[MEDLINE: 76063959]

Moffatt 1987 {published data only}

Moffatt ME, Kato C, Pless IB. Improvements in self-

concept after treatment of nocturnal enuresis: randomized

controlled trial. Journal of Pediatrics 1987;110(4):647–52.

[MEDLINE: 87168949]

Motavalli 1994 {published data only}

Motavalli N, Tuzun U, Tuna S, Yargic I, Aydogmus K.

Comparison of the effectiveness of three different treatment

modalities in enuresis nocturna. Noropsikiyatri Arsivi

(Archives of Neuropsychiatry - Turkish) 1994;31(3):146–50.

Nawaz 2002 {published data only}

Nawaz S, Griffiths P, Tappin D. Parent-administered

modified dry-bed training for childhood nocturnal enuresis:

Evidence for superiority over urine-alarm conditioning

when delivery factors are controlled. Behavioral Interventions

2002;17(4):247–60.

Netley 1984 {published data only}

Netley C, Khanna F, McKendry JB, Lovering JS. Effects

of different methods of treatment of primary enuresis on

psychologic functioning in children. Canadian Medical

Association Journal 1984;131(6):577–9. [MEDLINE:

85001664]

Ng 2005 {published data only}

Ng CF-N, Wong SN, Hong Kong Childhood Enuresis

Study Group. Comparing alarms, desmopressin, and

combined treatment in Chinese enuretic children. Pediatric

Nephrology 2005;20(2):163–9.

Rodriguez 2001 {published data only}

Rodriguez Do FA, Ariceta IG. Results of a therapeutic

strategy against monosymptomatic nocturnal enuresis

background. Anales Espanoles de Pediatria 2001;54(1):

38–43.

Ronen 1992 {published data only}

Ronen T, Rahav G, Wozner Y. Self-control and enuresis.

Journal of Cognitive Psychotherapy : An International

Quarterly 1995;9:249–58.∗ Ronen T, Wozner Y, Rahav G. Cognitive intervention in

enuresis. Child & Family Behaviour Therapy 1992;14(2):

1–14.

Sacks 1974 {published data only}

Sacks S, De Leon G, Blackman S. Psychological changes

associated with conditioning functional enuresis. Journal

of Clinical Psychology 1974;30(3):271–76. [MEDLINE:

74306370]

Scholander 1968 {published data only}

Scholander T. [Treating enuresis nocturna by a combination

of medicines and conditioning]. [Swedish]. Lakartidningen

1968;65(46):4552–6. [MEDLINE: 70200421]

Sloop 1973 {published data only}

Sloop EW, Kennedy WA. Institutionalized retarded

nocturnal enuretics treated by a conditioning technique.

American Journal of Mental Deficiency 1973;77(6):717–21.

[MEDLINE: 73241944]

Sukhai 1989 # {published data only}

Sukhai RN, Mol J, Harris AS. Combined therapy of enuresis

alarm and desmopressin in the treatment of nocturnal

enuresis. European Journal of Pediatrics 1989;148(5):465–7.

[MEDLINE: 89153190]

Taylor 1975 {published data only}

Taylor PD, Turner RK. A clinical trial of continuous,

intermittent and overlearning ’bell and pad’ treatments for

nocturnal enuresis. Behaviour Research & Therapy 1975;13

(4):281–93. [MEDLINE: 76061221]

Tobias 2001 {published data only}

Tobias NE, McCain GC. A comparison of two enuresis

alarms. Urologic Nursing 2001;21(5):349–53.

Turner 1970 {published data only}

Turner RK, Young GC, Rachman S. Treatment of nocturnal

enuresis by conditioning techniques. Behaviour Research &

Therapy 1970;8(4):367–91. [MEDLINE: 71062269]

van Londen 1993 {published data only}∗ van Londen A, van Londen-Barentsen MW, van Son

MJ, Mulder GA. Arousal training for children suffering

from nocturnal enuresis: a 2 1/2 year follow-up. Behaviour


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van Londen A, van Londen-Barentsen MW, van Son

MJ, Mulder GA. Relapse rate and subsequent parental

reaction after successful treatment of children suffering

from nocturnal enuresis: a 2 1/2 year follow-up of

bibliotherapy. Behaviour Research & Therapy 1995;33(3):

309–11. [MEDLINE: 95243898]

Wagner 1982 {published data only}

Wagner W, Johnson SB, Walker D, Carter R, Wittner J.

A controlled comparison of two treatments for nocturnal

enuresis. Journal of Pediatrics 1982;101(2):302–7.

[MEDLINE: 82241436]

Wagner 1985 {published data only}

Wagner WG, Matthews R. The treatment of nocturnal

enuresis: a controlled comparison of two models of urine

alarm. Journal of Developmental & Behavioral Pediatrics

1985;6(1):22–6. [MEDLINE: 85131790]

Werry 1965 {published data only}

Werry JS, Cohrssen J. Enuresis - an etiologic and therapeutic

study. Journal of Pediatrics 1965;67(3):423–31.



Wille 1986 {published data only}∗ Wille S. Comparison of desmopressin and enuresis alarm

for nocturnal enuresis. Archives of Disease in Childhood

1986;61(1):30–3. [MEDLINE: 86157697]

Wille S. Primary nocturnal enuresis in children. Background

and treatment. Scandinavian Journal of Urology &

Nephrology Supplementum 1994;156:1–48. [MEDLINE:

95025668]

Wright 1974 {published data only}

Wright L, Craig SC. A comparative study of amphetamine,

ephedrine-atropine mixture, placebo and behavioral

conditioning in the treatment of nocturnal enuresis. Journal

- Oklahoma State Medical Association 1974;67(10):430–3.

[MEDLINE: 75078843]

Young 1972 {published data only}∗ Young GC, Morgan RT. Overlearning in the conditioning

treatment of enuresis. Behaviour Research & Therapy 1972;

10(2):147–51. [MEDLINE: 72194405]

Young GC, Morgan RT. Overlearning in the conditioning

treatment of enuresis: a long-term follow-up study.

Behaviour Research & Therapy 1972;10(4):419–20.

[MEDLINE: 73051336]

References to studies excluded from this review


Azrin NH, Sneed TJ, Foxx RM. Dry bed: a rapid method of

eliminating bedwetting (enuresis) of the retarded. Behaviour


74097620]

Bollard 1977 {published data only}

Bollard RJ, Woodroffe P. The effect of parent-administered

Dry-Bed training on nocturnal enuresis in children.

Behaviour Research & Therapy 1977;15:159–65.

[MEDLINE: 77201386]

Bollard 1982b {published data only}

Bollard J, Nettelbeck T, Roxbee L. Dry-bed training

for childhood bedwetting: a comparison of group with

individually administered parent instruction. Behaviour


82231116]

Butler 2001 {published data only}

Butler RJ, Holland P, Robinson J. Examination of the

structured withdrawal program to prevent relapse of

nocturnal enuresis. Journal of Urology 2001;166(6):2463–6.

[MEDLINE: 21553451]

Collins 1973 {published data only}

Collins RW. Importance of the bladder-cue buzzer

contingency in the conditioning treatment for enuresis.

Journal of Abnormal Psychology 1973;82(2):299–308.

[MEDLINE: 74033838]

Crisp 1984 {published data only}∗ Crisp AH, Sireling LI, Faizey J. Nocturnal activity and the

enuresis alarm device. Postgraduate Medical Journal 1984;60

(702):280–1. [MEDLINE: 84221695]

Macaulay AJ, Gupta M, Crisp AH, Bhat AV. The

relationship between nocturnal motility and the enuresis

alarm device. Journal of Psychosomatic Research 1986;30(1):

63–5. [MEDLINE: 86199808]

de Leon 1966 {published data only}

De Leon G, Mandell W. A comparison of conditioning

and psychotherapy in the treatment of functional

enuresis. Journal of Clinical Psychology 1966;22(3):326–30.

[MEDLINE: 67014937]


Finley WW, Rainwater AJ, Johnson G 3d. Effect of varying

alarm schedules on acquisition and relapse parameters in the

conditioning treatment of enuresis. Behaviour Research &

Therapy 1982;20(1):69–80. [MEDLINE: 82159985]

Fordham 1989 {published data only}

Fordham KE, Meadow SR. Controlled trial of standard

pad and bell alarm against mini alarm for nocturnal

enuresis. Archives of Disease in Childhood 1989;64(5):

651–6. [MEDLINE: 89272170]

Forsyth 1970 {published data only}

Forsythe WI, Redmond A. Enuresis and the electric alarm:

study of 200 cases. British Medical Journal 1970;1(690):

211–3. [MEDLINE: 70105005]

Freyman 1963 {published data only}

Freyman R. Follow-up study of enuresis treated with a bell

apparatus. Journal of Child Psychology and Psychiatry 1963;

4:199–206.

Gillison 1958 {published data only}

Gillison TH, Skinner JL. Treatment of nocturnal enuresis by

the electric alarm. British Medical Journal 1958;ii:1268–72.

Goel 1984 {published data only}

Goel KM, Thomson RB, Gibb EM, McAinsh TF.

Evaluation of nine different types of enuresis alarms.

Archives of Disease in Childhood 1984;59(8):748–55.

[MEDLINE: 84305992]

Halliday 1987 {published data only}

Halliday S, Meadow SR, Berg I. Successful management

of daytime enuresis using alarm procedures: a randomly

controlled trial. Archives of Disease in Childhood 1987;62

(2):132–7. [MEDLINE: 87155424]

Hansen 1995 {published data only}

Hansen AF, Jorgensen TM. Treatment of nocturnal

enuresis with the bell-and-pad system. Scandinavian

Journal of Urology & Nephrology 1995;Suppl 173:101–2.

[MEDLINE: 96363554]

Hanson 1988 {published data only}

Hanson RH, Thompson T, Wieseler NA. Methodological

considerations in enuresis-treatment research. A three-

treatment comparison. Behavior Modification 1988;12(3):

335–52. [MEDLINE: 89149651]

Kahane 1955 {published data only}

Kahane M. An experimental investigation of a conditioning

treatment and a preliminary study of the psychoanalytic

theory of the etiology of nocturnal enuresis. American

Psychologist 1955;10:369–70.

Kaplan 1988 {published data only}

Kaplan SL, Breit M, Gauthier B, Busner J. A comparison of

three nocturnal enuresis treatment methods. Journal of the



American Academy of Child & Adolescent Psychiatry 1988;28

(2):282–6. [MEDLINE: 89174422]

Kooijman 1986 {published data only}

Kooijman MJ, Bosch JD. Supportive research on treatment

of enuresis with a urine alarm [dutch]. Nederlands Tijdschrift

voor Psychology en haar Grensgebieden 1986;41(7):325–8.

Kyneb 1975 {published data only}

Kyneb P, Biorn-Henriksen T. Treatment of enuresis of

schoolchildren with ’waking-apparatus’ [Behandling af

enuresis hos skoleborn ved vaekkeapparat]. Maanedsskrift

for Praktisk Laegegerning 1975;53(5):250–9.

Lovibond 1964d {published data only}




McConaghy 1969 {published data only}

McConaghy N. A controlled trial of imipramine,

amphetamine, pad-and-bell conditioning and random

awakening in the treatment of nocturnal enuresis. Medical

Journal of Australia 1969;2(5):237–9. [MEDLINE:

69296582]

Monda 1995 {published data only}

Monda JM, Husmann DA. Primary nocturnal enuresis: a

comparison among observation, imipramine, desmopressin

acetate and bed-wetting alarm systems. Journal of Urology

1995;154(2 Pt 2):745–8. [MEDLINE: 95333405]

Peterson 1969 {published data only}

Peterson RA, Wright RL, Hanlon CC. The effects on

extending the CS-UCS interval of the effectiveness of the

conditioning treatment for nocturnal enuresis. Behaviour


70138893]

Philpott 1970 {published data only}

Philpott MG. The treatment of enuresis; further clinical

experience with imipramine. British Journal of Clinical

Practice 1970;24(8):327–9. [MEDLINE: 71041622]

Said 1991 {published data only}

Said JA, Wilson PH, Hensley VR. Primary versus secondary

enuresis: differential response to urine-alarm treatment.

Child & Family Behaviour Therapy 1991;13(2):1–13.

Shulz 1978 {published data only}

Shulz D, Sureth H, Lubisch G. A comparison of two

behaviour therapeutic methods in the treatment of enuresis.

Zeitschrift fur Klinische Psychologie 1978;7(2):141–8.

Taylor 1963 {published data only}

Taylor IO. A scheme for the treatment of enuresis by electric

buzzer apparatus. Medical Officer 1963;110:139–340.

Wickes 1958 {published data only}

Wickes IG. Treatment of persistent enuresis with the electric

buzzer. Archives of Disease in Childhood 1958;33:160–4.

Young 1965 {published data only}

Turner RK. CNS stimulant drugs and conditioning

treatment of nocturnal enuresis: a long term follow-up

study. Behaviour Research & Therapy 1966;4(3):225–8.

[MEDLINE: 66171102]∗ Young GC, Turner RK. CNS stimulant drugs and

conditioning treatment of nocturnal enuresis. Behaviour

Research & Therapy 1965;3:93–101.

References to ongoing studies

Bryant 2002 {published data only}

Bryant C, Fairbrother G. Randomised trial of bladder

training versus enuresis alarm versus combined bladder

training/enuresis alarm in children with nocturnal enuresis.

personal communication 2002.

Additional references

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References to other published versions of this review

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nocturnal enuresis in children. The Cochrane Database of

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Systematic Reviews 2005, Issue 2.

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Systematic Review of the Effectiveness of Interventions for

Managing Childhood Nocturnal Enuresis. NHS Centre for

Reviews and Dissemination. Vol. CRD Report 11, York,

UK: University of York, 1997.∗ Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Azrin 1974

Methods RCT - coin flip used to randomise each of pairs of children

Systematic baseline measure of wetting: Yes

Organic causes excluded: Yes

Daytime wetting: Not mentioned

Setting: respondents to a newspaper advertisement for enuretics

Participants No. of children (boys): 26 (19)

Excl: medical causes

Ages: 3+, mean 8 years

Baseline frequency 7 days/week.

Interventions Experiment 1

A (7): DBT (parent-and-child alarm; PP; W; increasing fluid intake; rewards; CT; training in inhibiting

urination

B (7): Child-only alarm for first 2 weeks only, then DBT

Experiment 2

C (6): DBT, parent-only alarm

D (6): Child-only alarm

Outcomes Fewer wet nights in first 2 weeks with A+C (median 1 vs B+D 5 in second week, P<0.005).

More children achieving 6 dry nights in A

Notes Pairs matched for age, sex and frequency of wetting

No useable data.

Risk of bias

Item Authors’ judgement Description

Allocation concealment? Yes A - Adequate

Azrin 1978

Methods RCT (details not given)



Daytime wetting excluded: Yes


Incl: Age at least 3 years; no daytime wetting; wetting at least 4x/week; able to understand instructions;

medical examination and treatment

Age: mean 7 years (range 3-14) (20 less than 6 years)

Baseline wetting: 91% of nights



Azrin 1978 (Continued)

Interventions A (28): Intensive DBT (PP, CT) plus rehearsing during the day with increased fluid intake, stream inter-

ruption exercises, Retention Control Training, repeated awakening, rewards for dry nights or compliance

but NO ALARM

B (27): Alarm (pad-and-buzzer)

Duration of trial: 2 weeks, after which parents could swap to other arm

Outcomes Per cent wet nights during 2 weeks: A, 15%; B, 76%

No. of children swapping to other group after 2 w: A, 0/27; B, 23/27

Notes Comparability of groups at baseline not reported

No follow up possible after 2 weeks

No SDs

Very young children (20 under age 6 years) included

Risk of bias


Allocation concealment? Unclear B - Unclear

Baker 1969

Methods RCT

Systematic baseline measure of wetting: No


Daytime wetting excluded: Not mentioned

Setting: recruited from newspaper advertisement


Incl: primary (26) and secondary (4) enuresis

Age median 8 years, range 6-12

Baseline wetting: half wetting every night

Interventions A: (10) Alarm

B: (10) Wake up using alarm clock, and star chart

C: (10) Waiting list control

Duration of treatment: 10 weeks, or 50 wet episodes

Outcomes Mean no. wet nights per week in last 3 weeks of treatment: A, 1.8; B, 3.1; C, 5.9 (no SDs)

Minor behavioural adverse events, self limiting

Notes Waiting list controls subsequently given an intervention, results not presented separately

No SDs given

Risk of bias




Baker 1969 (Continued)


Bennett 1985

Methods RCT


Organic causes excluded: Not mentioned

Daytime wetting excluded: Yes if only negligible


Dropouts: 32 (A,9; B,11; C,10; D,3)

Incl: primary nocturnal enuresis, referred to enuresis service by GP, negligible daytime wetting

Excl: encopresis, previous behavioural intervention, gross psychopathology

Age mean 8.5 years (SD 3.2) range 5-12

Baseline wetting: dry nights, boys 3/14; girls 2.4/14

Interventions A: (9) Alarm (pad and buzzer)

B: (12) Stop-start training (sphinchter muscle exercises, bladder training)

C: (10) Dry Bed Training including alarm

D: (9) Waiting list control (used star chart after first dry night)

Duration of treatment: 10 weeks

Outcomes Mean dry nights in last 2 weeks of 12 weeks treatment: A, 12 (SD 3.9); B, 7.5 (5.2); C, 11.2 (3.6); D, 3.

7 (3.0)

No. achieving 14 dry nights:

A, 4/9; B, 2/12; C, 5/10; D, 0/9

Mean dry nights at followup:

A, 12.3 (3.1); B, 7.1 (5.8); C, 9.3 (5.3). (D treated after 12 weeks)

Adverse events: not mentioned

Notes All children got star charts after their first dry night

High dropout rate

Risk of bias



Bollard 1981a

Methods RCT






Bollard 1981a (Continued)

Participants Experiment 1

No. of children (boys): 45 (A:11, B:11, C:10)

No. of dropouts: A:0, B:3, C: 0

Incl: No underlying organic pathology

Previous treatment: no details

Mean age (years.months): A: 9.10 B: 9.9 C: 9.5

Baseline wetting: Mean number of wet nights per week: A: 5.3 B: 5.4 C: 4.2


A (15): enuresis alarm - supervised (weekly followup) B (15): enuresis alarm - unsupervised

C (15): waiting list control

Duration of treatment: until achievement of 14 consecutive dry nights or 20 weeks

Follow up: 3, 6 and 12 months

Outcomes Experiment 1

Mean number of wet nights at end of 20 weeks: A:0.8, B:2.2, C:4.6

2 treatment groups did not differ significantly in number of wet beds at end of 20 weeks or number of

days taken to reach dryness criterion

Number achieving 14 consecutive dry nights: A:12, B:9, C:0

Number relapsing at 12 m followup: A:4, B:5

Notes Experiment 1

No blinding

Comparability of groups not reported

Graphical data

No SDs

No baseline data for control group

Two analyses provided:

a) intention to treat basis;

b) excluding dropouts

Risk of bias



Bollard 1981b

Methods RCT





No. of children: 100

No. of boys: A:14 B:13 C:16 D:14 E:14 F:11

No. of dropouts: 12 from D



Bollard 1981b (Continued)

Incl: thorough medical examination; regularly wetting at least one night per week; no other treatment

during trial


Mean age (years.months): A:9.3 B:8.11 C:9.7 D:8.6 E:8.8 F:8.10

Baseline wetting: mean number of wet nights: A:5.8 B:5.2 C:6.0 D:5.7 E:6.0 F:4.7


A (20): DBT (A + W + CT + PP) with therapist at home

B (20): DBT (A + W + CT + PP) with therapist at hospital

C (20): DBT (A + W + CT + PP) with parents as therapists at home

D (20): DBT (W + CT + PP) with parents as therapists at home WITHOUT enuresis alarm

E (20): alarm

F (20): waiting list control

Duration of treatment: until 14 consecutive dry nights or 20 weeks

Follow up at 3, 6 and 12 months


Comparing DBT with alarm only - DBT significantly more effective in terms of number of wet nights

and days to dryness

Mean number of wet nights per week at end of week 20

(incl dropouts) A:0, B:0, C:0, D: (n=20) 3.8, E: 0.6, F: 4.4

(excl dropouts) A:0, B:0, C:0, D:(n=8) 1.3, E:0.6, F:4.4

No. achieving 14 consecutive dry nights: A:20, B:20, C:20, D:5, E:16, F:2

(p < 0.05)

No. relapsing: A:5, B:6, C:4, D:2, E:6, F:2 NS

ie no. failing or relapsing: A: 5/20, B: 6/20, C: 4/20, D: 17/20, E: 10/20, F: 20/20

Notes Experiment 2

No details of blinding

DBT no alarm group (D) younger than others and

more girls in waiting list control group (F)

No SDs

Analysed on intention to treat basis and with dropouts included

Risk of bias



Bollard 1982a

Methods Mainly RCT but also comparison with previous study [A] and [H] from another study






Bollard 1982a (Continued)

Participants No. of children (2 groups combined) (boys): 127 (88)

Incl: no underlying organic pathology

Previous treatment: many had previously sought help but none undergoing any form of enuresis related

drug or psychotherapy at the time of the study.

Mean age: 9 yrs 10 m

Baseline wetting: Overall mean number of wet nights per week = 5.5

Interventions [A (35): alarm only (A)]

B (12): alarm (A) + waking schedule (W)

C (12): A+retention control training

D (12): A+ positive practice (PP)+ cleanliness training (CT)

E (12): A+W+retention control training

F (12): A+W+PP +CT

G (12): A+retention control training+PP +CT

[H (20): Full DBT]


Follow up: none

Outcomes Mean no. of wet nights during 20 week treatment period:

A: 27 B: 13 C: 24 D: 23 E: 14 F: 10 G: 21 H: 11

Number of cases becoming dry: A: 31 B: 12 C: 11 D: 10 E: 12 F: 12 G: 11 H: 20

Significant difference in response rate of group with waking schedule vs those without (Chi squared = 13.

04, df = 3, p < 0.01)

Notes Groups A and H from another trial, data not used

No analysis of comparability of groups

No blinding

No SDs

No follow up

Risk of bias



Bradbury 1995

Methods RCT (quota allocation system based on age, baseline wetting, family or housing problems, gender, previous

alarm use, daytime wetting and previous dry periods)



Daytime wetting excluded: No

Participants No. of children: 71 (boys 48)

Dropouts A: 3, B: 8

Incl: nocturnal enuresis at least 1 night per wk (40/71 = severe, >4x/week);

Excl: neuropathic bladder, urinary tract abnormalities, cystic fibrosis, allergic rhinitis, deafness/learning



Bradbury 1995 (Continued)

difficulties, UTI

Previous treatment: 29 had used alarms

Interventions A (36): desmopressin 40 mcg intranasally + alarm (bell-and-pad or Mini Drinite)

B (35): alarm alone

Duration of treatment: 6 weeks or until dry

Follow up: 6 months

Outcomes Mean DRY nights/week: A: n=33, mean = 6.1 95% CI 5.6-6.7; B: 27, 4.8, 4.0-5.6

No. not achieving 4 dry nights: A: 6/33; B: 11/27

No. failing + no. relapsing: A: 10/33; B: 14/27

Side effects: none reported

Subgroup analysis in more severe group: A still better than B

Notes Mini Drinite = body-worn alarm

Relapsing = >2 wet nights in 2 weeks after 4 weeks dry

Authors recommend using combined desmopressin + alarm only for children with severe wetting problems

Risk of bias



Butler 1988

Methods RCT




Participants No. of children (boys): 74(A: 18, B: 29)

Dropouts: 11 excluded after baseline assessments

Incl: age at least 6 years;wetting at least five nights a week for a month; normal clinical exam; normal

urine on microscopy; normal intelligence (assessed by reference to educational background and parental-

child interview); not having any form of enuresis related drug or psychotherapeutic treatment

Previous treatment: 36 (48.6%) enuresis alarm

Mean age: A: 8.99 B: 9.86

Baseline wetting: mean number of dry nights during 4 weeks

A: 1.07 B: 1.02

Interventions A (28): Standard enuresis alarm treatment (A)

B (35): Modified DBT + alarm (A + W + PP + retention control training) WITHOUT reprimands during

CT


Follow up: none



Butler 1988 (Continued)

Outcomes Mean number of dry nights in last 4 weeks

A:20.76 B:23.79 F(1,46) = 1.77

Number of children achieving 14 dry night criterion

A:20/28 (71%) B: 25/35 (71%) no significant difference

Mothers in dropout group significantly more angry with bedwetting than other groups

Notes No significant difference between groups for demographic factors but modified-DBT group more likely

to have previously used alarm. Analysis of covariance adjusted for the effects of previous experience with

enuresis alarm

No blinding

Not intention to treat

No SDs

Risk of bias



Butler 1990a

Methods CCT (alternate allocation)

Experiment 1





No. of children: 40 (boys A: 14 B: 11)

Dropouts A: 3 B: 2

Incl: wetting at least 4 nights a week for a month; normal physical examination; normal urine microscopy;

normal intelligence (assessed by reference to educational background and parent\child interview)

Previous treatment: None

Mean age: A: 8.2 B: 9.1

Baseline wetting: mean number of DRY nights per week: A: 1.2 B: 0.7

No significant difference between groups on any variable


A (20): pad and bell alarm

B (20): body worn alarm


FU after 6 months


Mean number of wet nights in 16 weeks: A: 18.9 B: 15.3

Number (%) children achieving 14 consecutive dry nights: A: 14 (70) B: 14 (70)

Mean number of wet nights until achievement of 14 consecutive dry nights A: 54.8 B: 35.3 (t = 2.8, df =

26, p < 0.01)



Butler 1990a (Continued)

Number (%) children relapsing A: 4/14 (29) B: 3/14 (21)

The majority of children preferred body-worn alarm to pad and bell

Notes Small groups

Experiment 1

No blinding

Unclear if intention to treat analysis

Poor randomisation

No SDs

Risk of bias


Allocation concealment? No C - Inadequate

Butler 1990b

Methods CCT (alternate allocation)

Experiment 2





No. of children: 48 (boys A: 20 B:20)

Number of dropouts: A: 2 B 1

Incl: wetting at least 4 nights a week for a month; nomal physical examination; normal urine microscopy;

normal intelligence (assessed by reference to educational background and parent\child interview); no

associated diurnal enuresis

Previous treatment: unsuccessful treatment with pad and bell alarm

Mean age (years): A: 10.2 B: 11.2

Severity at baseline: mean number of DRY nights per week: A: 1.2 B: 1.3

Groups did not differ significantly on any variable


A (24): Modified DBT + pad-and-bell alarm (A + W + retention control training)

B (24): body-worn alarm (A)


FU after 6 months


Mean number of wet nights in 16 weeks A: 28.7 B: 25.0

Number (%) attaining 14 consecutive dry nights A: 14 (58) B: 20 (83)

Mean number of wet nights to achievement of 14 consecutive dry nights A: 53.7 B: 40.7

Number (%) children relapsing: A: 7 (50) B: 9 (45)



Butler 1990b (Continued)

Notes Experiment 2

Unclear if intention to treat analysis

Poor randomisation

No SDs

Dry bed training included a pad-and-bell alarm, a waking schedule and retention control training

Risk of bias



Caceres 1982

Methods RCT ’double blind’


Organic causes excluded: No



Incl: enuresis, or behaviour problem + enuresis. Some were not daytime toilet trained

Previous treatment: all had failed with psychotherapy, drugs or fluid restriction

Age: mean 9 years (range 6-14)

Baseline wetting: every night

Interventions A (7): Enuresis alarm (Mowrer’s pad-and-bell)

B (7): DBT (but WITHOUT alarm) + rewards

Duration: 1 m, then crossed over to other arm if not 50% improved

Outcomes Not cured on original treatment: A: 0/7, B: 5/7

Notes Children crossed over to alternative treatment if not successful (5 of B group changed to A). Cure rates

given while on first treatment

Risk of bias





Danquah 1975

Methods RCT - but mention of matching




Setting: Ghanian fishing community

Participants No. of children (boys): 30 (all boys)

Excl: more than a week of traditional treatment

Mean age: 10 .4 years

Mean frequency of wetting at baseline: A: 5.6 B: 4.00 C: 3.20

Interventions A (10): traditional shaming

B (10): amitriptyline hydrochloride

C (10): alarm


Follow up after 3 months

Outcomes Mean frequency of wetting after treatment: A: 5.6; B: 4.00; C: 3.2

Subjects of traditional shaming seemed depressed and evidence of loss of self esteem and patients isolating

themselves from friends.

Drug treatment was said to cause drowsiness at first. Parents not disturbed by alarm because they slept

outside

Notes No details of dropouts

No SDs

No details of previous treatment

Groups comparable in age and intelligence

Traditional shaming consisted of being carried from home by a singing mob and being thrown into the

lagoon

Risk of bias



Elinder 1985

Methods RCT





No. of dropouts: A:9; B:6 due to technical problems or discomfort

Incl: Age at least 7 years; primary nocturnal enuresis; at least 3 wet nights/week; no daytime wetting

Excl: physical or psychological /psychiatric disease

Previous treatment: tricyclics (A:20, B:7); alarm (1, 2)



Elinder 1985 (Continued)

Ages: 39 7-11 years; 14 over 11 years

Interventions A (36): Functioning Uristop device

B: (17) Non-functioning Uristop device


Follow up 12 months

Outcomes No. not cured: A: 0/36, B: 0/17

Notes Device delivers electric impulse to pudendal nerve in groin when urine is passed

Power calculation given

Groups comparable at baseline except more upsetting life events and psychiatric contact in B

Failure ascribed to incorrect theory or incorrect construction (wrong placement of electrodes or impulse

too low)

Risk of bias



Faraj 1999

Methods RCT (random number tables, details not given)




Participants No. of children: 135

Dropouts: 23 excluded for non-compliance, and 39 lost to follow up including 12 failed with alarms

Incl: monosymptomatic nocturnal enuresis, age >5 years

Excl: previous treatment with desmopressin or alarm, urological pathology, diurnal enuresis, UTI

Age mean 11.2 years

Baseline wetting A 21% dry nights, B 14% dry nights

Interventions A (62): Desmo 20 µg intranasally increasing to 40 µg if response partial

B (73): alarm (pad-and-bell)

Duration of treatment 3 m. If failed at that time, changed to alternative arm Follow up: none

Outcomes DRY nights at 3 months: A 85%; B: 90%

No. not achieving 14 dry nights: A 12/39; B: 6/37

Side effects: not mentioned

Notes

Risk of bias




Faraj 1999 (Continued)


Fielding 1980

Methods RCT




Participants No. of children (boys): 45 (6 lost at baseline) (30)

Dropouts: 11

Incl: age 5 to 15; no urinary tract infection; no evidence of organic pathology; not treated within previous

12 months; no daytime wetting

Age range: 5 years 2 months to 13 years 10 months

Baseline wetting: mean number of wet nights in 4 weeks: A: 23.5 B: 24.7

Interventions A: (16) retention control training and enuresis alarm

B: (17) enuresis alarm alone

Duration of treatment: retention control training 4 weeks and alarm 14 weeks

Follow up after 3, 6 and 12 months

Outcomes Mean number of wet nights in 3rd month of alarm: A, 6.2; B, 2.3

Number achieving 14 consecutive dry nights: A, 11/16; B, 14/17

Number (%) relapsing after 3 months: A, 3 (28); B, 4 (29)

after 6 months: A, 3 (28); B, 5 (36)

after 12 months: A, 4 (36); B, 8 (57)


Notes Analysed on intention to treat basis

Parallel study specifically includes diurnal wetters (results not given here)

No blinding

Not reported if comparable groups

No SDs

Risk of bias





Finley 1973

Methods RCT




Setting: Children’s Medical Centre, Tulsa, Oklahoma USA


Incl: primary nocturnal enuresis, at least 3 wet nights/week, own room and bed

Excl: daytime wetting, organic cause for enuresis, emotional disturbance

Ages: 6 to 8 years

Baseline wetting: 3x/week, 7 to 8 wet episodes per week

Interventions A (10): enuresis alarm (105 dB bell) + light

B (10): enuresis alarm (80 dB bell), intermittent action (70% active)

C (10): alarm (78 dB) in parents’ room 20 mins after wetting

Duration of treatment 6 weeks

Follow up 3 months

Outcomes Mean wet episodes during 6th week: A: 0.2, B: 0.6, C: 8

No. not achieving 7 dry nights: A: 1/10, B: 2/10, C: 10/10

No. failing or relapsing after ’cure’: A: 5/10, B: 3/10 (C all failed: 10/10)

Notes No SDs

Data estimated from graph

Risk of bias



Finley 1977

Methods RCT




Setting: Children’s Medical Centre, Tulsa, Oklahoma USA


Incl: primary nocturnal enuresis

Excl: emotional disturbance, organic causes, daytime wetting

Age: 6-9 years

Baseline wetting: 6-7 wet nights/week

Interventions A (10): alarm with 105 dB bell

B (10): alarm with 80 dB bell




Finley 1977 (Continued)

Follow up 16-24 months

Outcomes No. not achieving 14 dry nights: A: 3/10, B: 6/10

Relapse rate: A: 3/7, B: 1/4

Failed or relapsed: A: 6/10, B: 7/10

Notes Group comparability at baseline not stated

Risk of bias



Forrester 1964

Methods RCT




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 1x/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


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





Fournier 1987

Methods RCT (double-blind)




Participants No. of children (boys): 64 (47) completed the study

5 extra children dropped out

Incl: no treatment in past 3 months

Mean age: 8 years 5 months

Baseline wetting: mean number of wet nights in week 2: A, 5.3; B, 6; C, 4.5; D, 4.2; E, 4.5

Interventions A (8): imipramine

B (8): enuresis alarm

C (8): placebo

D (8): random awakening

E (8): alarm + imipramine

[F (8): Alarm + placebo

G (8): random awakening + placebo

H (8): imipramine + random awakening]


Follow up 3 months but some children continued on treatments

Outcomes Mean number of wet nights per week:

A: 1.9 B: 2.5 C: 5 D: 3.3

E: 1

No results for F, G or H

4 boys dropped out because of side-effects or non-compliance, 1 girl with UTI

Notes Parallel groups

No SDs

Differences in baseline severity of wetting - MANOVA used

Risk of bias



Geffken 1986a

Methods RCT

Children were stratified by maximal functional bladder capacity




Participants No. of children (boys): initially 50

(Boys: A: 8 C: 6)



Geffken 1986a (Continued)

10 dropouts

Incl: nocturnal enuresis of at least 3 months duration; at least 2 wetting episodes a week

Mean age A: 9.0 C: 9.4

Baseline wetting: Mean (SD) number of wet nights per week

A: 4.9 (1.7) C: 5.4 (1.1)

Interventions Large maximal functional bladder capacity:

A (10): alarm

C (10): alarm + retention control training


Follow up after 8 or more weeks

Outcomes Mean (SD) number of wet nights per week A: 1.7 (1.2) C: 2.5 (0.9)

Significant interaction between maximal functional bladder capacity and treatment F(1, 33) = 4.90, p 0.

03

Number of children achieving initial arrest during 14 weeks treatment A: 9 C: 9

Number of children relapsing during follow up A: 3 C: 4

Notes Not intention to treat analysis

Short follow up


Payment required

For those who completed treatment there were no significant difference between the groups in terms of

sex, age, child adjustment measures or the Tolerance and Nuisance Scales

Retention control training consisted of increasing fluid intake and delaying urination for increasing periods

of time to expand bladder capacity

Risk of bias



Geffken 1986b

Methods RCT




Participants No. of children (boys): initially 50

(Boys: B: 5 D: 6)

10 dropouts

Incl: nocturnal enuresis of at least 3 months duration; at least 2 wetting episodes a week

Mean age B: 7.7 D: 8.0

Baseline wetting: Mean (SD) number of wet nights per week

B: 5.7 (1.3) D: 4.9 (1.2)



Geffken 1986b (Continued)

Interventions Small maximal functional bladder capacity:

B (10): alarm

D (10): alarm + retention control training


Follow up after 8 or more weeks

Outcomes Mean (SD) number of wet nights per week

B: 2.3 (1.0) D: 1.6 (1.1)

Significant interaction between maximal functional bladder capacity and treatment F(1, 33) = 4.90, P=0.

03

Number of children achieving initial arrest during 14 weeks treatment B: 10 D: 9

Number of children relapsing during follow up B: 6 D: 3

Notes Not intention to treat analysis

Short follow up


Payment required

For those who completed treatment there were no significant differences between the groups in terms of

sex, age, child adjustment measures or the Tolerance and Nuisance Scales

Retention control training consisted of increasing fluid intake and delaying urination for increasing periods

of time to expand bladder capacity

Risk of bias



Gibb 2004

Methods RCT (drug dispensed randomly by pharmacist)




Setting: Paediatric outpatients, Children’s Hospital, Melbourne, Australia

Participants Number of children (boys): 207/210 (A:64, B:78)

Dropouts: 10 eligible children declined, incomplete data on A:9/101, B:17/106 but dropouts counted as

failures for analysis

Inclusion criteria: Non-responders to desmopressin treatment (<50% reduction in wet nights), age 6-16

years, wetting at least twice per week, some daytime wetting (A:11, B:8)

Exclusion criteria: Neuropathic bladder, urinary tract abnormality, cystic fibrosis, allergic rhinitis, UTI in

previous 2 weeks, imipramine or diuretics

Previous treatment: some had alarm (A:37, B:32) or desmopressin (A:31, B:28)

Age: mean 9.4 years (SD 2.08)

Baseline wet nights in 28 days: A: 23.9 (SD 5.05), B: 23.7 (5.83)



Gibb 2004 (Continued)

Interventions A (84/101): desmopressin (40 µg nasal spray) + alarm (pad and bell)

B (85/106): placebo (nasal spray) + alarm (pad and bell)


Follow up: 2 months

Outcomes Cure = 28 dry nights, relapse = 2 wet nights in 2 weeks

Wet nights during treatment (number, mean (SD)): A: 101, 1.8 (1.13), B: 106, 2.4 (1.53)

Cure during treatment: A: 52/101, B: 51/106 P=0.63 (failed: A: 49/101, B: 55/106)

Relapse after treatment stopped: A: 7, B: 3

Failed or relapsed: A: 56/101, B: 58/106

Adverse effects: A: 1 (headache), B: 1 (nose bleed)

Other: compliance same in both groups

Cure in daytime wetting: A: 6/11, B: 3/8

Notes Intention to treat analysis

Groups comparable at baseline on age, wetting, gender, family history, secondary enuresis, daytime wetting

and previous treatment

Risk of bias



Hojsgaard 1979

Methods RCT




Participants No. of children (boys): 62

Interventions A (32): Uristop device

B (30): no treatment

Outcomes Cured: A: 20/32, B: 17/30

Improved: A: 5/32, B: 6/30

Notes Norwegian language

Uristop device gives ’electrical stimulation’ to the children

Risk of bias





Houts 1986

Methods RCT




Setting: media recruitment and paediatric referrals


Dropouts: A: 2, B: 2, C: 3

Incl: Primary enuresis

Age 5-13 years

Baseline wetting: mean 5.41 (SD 1.63) wet nights/week

Interventions A (15): Enuresis alarm + over-learning + retention control training (Full Spectrum Home Training Package)

B (15): Enuresis alarm + retention control training

C (15): Enuresis alarm alone

D (11): Waiting list control


Follow up: 1 year

Outcomes A: cured 9, failed 4, dropout 2; B: cured 13, dropped out 2; C: cured 9, failed 3, dropped out 3; D none

cured (11/11 failed)

Relapse at end of study after retreatment if necessary: A: 1, B: 6, C: 3

ie. failed or relapsed: A 5/13, B: 6/13, C: 6/12

Notes Groups comparable at baseline

A, B + C received 1 hour group training and CT

Relapses were retreated with initial treatment allocated

Children who failed were older, and dropouts were younger

Risk of bias



Jehu 1977

Methods RCT

Analysis curtailed after 12 weeks to accomodate the loss of some control children




Setting: Children resident in Children’s Homes but attending normal rather than special school so that

treatment not impractical -eg children only spent weekends or school holidays at the home

Participants No. of children (boys): 39 (boys A: 8 B: 17)

1 dropout

Incl: age 4 years or over; wetting frequency of at least 4 nights per week during baseline; not previously



Jehu 1977 (Continued)

treated by alarm within last year; no gross physical handicap

Previous treatment: drug therapy (7), alarm treatment (2)

Mean age 9 years 4 months (range 4 years 9 montha to 14 years 7 months)

Baseline wetting: For treatment group only mean no. wet nights per week = 4

Interventions A (19): enuresis alarm

B (20): no treatment control

Duration of treatment: 3 or 4 months - until success achieved (achieved 14 dry nights)

Follow up: after 6 months then 20 months

Outcomes Mean number of wet nights in week 12: A: 0.3 B: 5.3

Achieved 14 dry nights: A: 18/19 B: 0/20

One had absconded (counted as failure)

3 children had relapsed at 6 months and another at 8 months (needed repeat treatment)

Notes Comparability of groups not reported

No baseline for control - probably should compare from week 4 for control to compensate for this


More girls in alarm group

No SDs

Risk of bias



Kennedy 1968

Methods RCT (alternate allocation)




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


Follow up: 13 months

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



Kennedy 1968 (Continued)

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



Kolvin 1972

Methods RCT





2 dropouts

Incl: wetting at least 3 nights a week; age range (not stated); not receiving treatment elsewhere


Mean age: 9 years 4 months (range 8 to 10)

Baseline wetting: mean number of wet nights per month A: 22.7 B: 22.0 C: 20.9


B (32): pad and buzzer alarm

C (27): placebo

Duration of treatment: 2 months

Follow up: after 4 months

Outcomes Mean number of wet night in final month (% improvement)

A: 9.3 (64) B: 9.1 (62) C: 11.0 (53)

At follow up mean number of wet nights per month (% improvement)

A: 13.4 (43) B: 9.3 (64) C: 11.3 (54)

Notes No details of blinding

Not reported if comparable groups


No SDs

Risk of bias





Leebeek 2001

Methods RCT (double blind parallel group study)





Incl: at least 6 wet nights/week

Excl: treatment in previous 2 weeks; daytime wetting/pollakisuria; urological or psycholigical disease; poor

motivation to use alarm

Previous treatment: none in previous 2 weeks

Age: 6-14 years

Baseline wetting: mean number of wet nights: A: 6.14, B: 6.12 (not significant)

Interventions A (47) alarm + desmo 40 µg intranasal for 3 weeks, then alarm + desmopressin 20 µg for 3 weeks, then

alarm alone for 3 weeks

B (46): alarm + placebo for 6 weeks, then alarm alone for 3 weeks

Follow up: at 2 weeks and 6 months after end of trial

Outcomes (Number), mean wet nights:

1st 3 weeks: A: (47), 2.93, B: (45), 3.86 (P=0.014)

Last 3 weeks, alarm only: A: 43, 2.77, B: 39, 2.21

Cured 2 weeks after end of trial: A: 15/47, B: 17/46

Cured 6 months after end of trial: A: 17/47, B: 17/46

ie failed at 6 months: A: 20/47, B: 21/46

Mean wet nights at 6 months: A: 41, 2.72, B: 37, 1.90

Adverse events: none in either group

Notes Power calculation provided

SDs not given (authors contacted for more information)

Groups comparable for sex and age

Study supported by drug company (Ferring)

Risk of bias



Longstaffe 2000

Methods RCT (computer generated randomisation)




Setting: recruited from hospital clinic and advertising



Longstaffe 2000 (Continued)


At 6 months 17 withdrew due to failure (A 8; B 5; C 4)

Incl: primary monosymptomatic nocturnal enuresis, age >7 years, wet >3 x/week, normal bladder capacity

Excl: daytime wetting, CNS disorder, developmental delay, current alarm or desmopressin treatment,

encopresis, other medical problems

Interventions A (61): alarm

B (60): desmopressin intranasally

C (61): placebo

Duration of treatment: 6 months, then failures crossed over to alternative arm for 6 months (not ran-

domised)

Outcomes No. not achieving 14 dry nights after 6 months: A: 26/61; B: 31/60; C: 38/61

All children improved psychologically, e.g. behaviour and self concept, regardless of outcome or treatment

assignment

Side effects: not mentioned

Notes Dose of desmopressin not given

No follow up as failures assigned alternative treatment

Blinding to method not possible for alarm group

Risk of bias



Lovibond 1964a

Methods RCT (stratified by age and sex)




Setting: school children and GP referrals


Dropouts: B: 2

Incl: wet at least 3x/week; co-operative families

Excl: organic causes

Ages: 6 to 7 years 5 months: 7 years 6 months to 10 years 5 months: 10 years 6 months to 14


A (12): Twin signal alarm (hooter then buzzer) + ’escape training’

B (12): Crosby Dri-nite (pad electrode but no genital electrode)

C (12): Mowrer pad-and-bell

Duration of treatment: until 14 dry nights achieved, fluid intake increased if dry for 7 nights (=overlearning)

or 50 days




Lovibond 1964a (Continued)


No. not achieving 14 dry nights: A 0/12, B: 6/12, C: 1/12

No. failing or relapsing after trial: A: 5/12, B: 6/12, C: 5/12

Adverse events: B: corrosive skin burns (3); discontinued due to fear of shocks (2)

Notes

Risk of bias



Lovibond 1964b

Methods RCT (stratified by age, sex and wetting frequency)




Participants No. of children (boys) 20 (12)



Ages: 8-12 years


A1 (5): Twin signal alarm triggered by wetting

A2 (5): Twin signal alarm but parents (not wetting) triggered the alarm after 2 dry nights (false alarm)

B1 (5): Mowrer pad-and-bell alarm triggered by wetting

B2 (5): Mowrer pad-and-bell alarm but parents (not wetting) triggered the alarm after 2 dry nights (false

alarm)

Duration: until 14 dry nights achieved including increased fluid intake after 7 dry nights (=overlearning)

or 50 days

Follow up: 24 m


No. not achieving 14 dry nights: A1: 0/5, A2: 0/5, B1: 0/5, B2: 0/5

No. failing or relapsing after 24 months: A1: 3/5, A2: 3/5, B1: 3/5, B2: 2/5 or:

Standard (A1 + B1) 6/10 vs False (A2 + B2) 5/10

Notes ’False’ alarm equivalent to ’waking’ by parents

Data from ’standard’ vs ’false’ only used

Risk of bias




Lovibond 1964b (Continued)


Lovibond 1964c

Methods RCT (stratified by age and sex)




Participants No. of children (boys) 24 (12)




A (12): Modified Twin Signal (bell instead of buzzer, then second weaker alarm)

B (12): Mowrer pad-and-bell alarm

Duration: until 14 dry nights achieved including increased fluid intake after 7 dry nights (=overlearning)

or 50 days



No. not achieving 14 dry nights: A: 0/12, B: 2/12

No. failing or relapsing: A: 5/12, B: 6/12

Notes

Risk of bias



Lynch 1984

Methods RCT




Setting: School or paediatric referrals


No. of dropouts: A:2, B:2, C:2

Incl: at least 2 wet nights/week

Excl: daytime wetting

Ages: 5-12

Baseline wetting in 14 nights, mean (SD): A: 11.11 (2.9), B: 11.33 (2.99), C: 11.55



Lynch 1984 (Continued)

Interventions A (20): star chart for 2 weeks then enuresis alarm - immediate

B (20): star chart for 2 weeks then enuresis alarm - 3 minute delay + CT

C (20): control, no treatment


Follow up: None

Outcomes Wet nights in last 2 weeks, n, mean (SD): A: 18, 3.38 (4.55), B: 18, 8.38 (4.55), C: 18, 8.11 (3.25)


Notes Groups comparable at baseline

One dropout from alarm group due to stress from alarm

Risk of bias



McKendry 1975

Methods RCT




Setting: Paediatric outpatients, Toronto, Canada


No. of dropouts: 53 (A: 9, B:12, C:32)

Incl: primary nocturnal enuresis, ’a few’ had diurnal wetting


Ages: Mean 9 years (range 5-17)

Baseline wetting (self reported): A: 83.4%, B: 82.3%, C: 87.4%

Interventions A (73): restricted diet

B (74): imipramine 10 mg at bedtime, increased to max 40 mg for age 5-9, up to 60 mg for 10+

C (75): Mozes Detector (body-worn detector, sounds alarm + delivers electric shock when a few drops of

urine pass)


Follow up: A: 3 months, B: 19 months, C: 14 months

Outcomes No. not achieving 14 dry nights: A: 63/64, B: 49/62, C: 20/43

Adverse events: A: 2/12 children became aggressive; B: 3/16 had headaches, abdominal pain or fatigue,

C: 10/16 showed fear or anxiety about the machine. For C, electric shocks resulted in skin erythema,

discolouration, painless cold burns and ulceration

Notes Diet = no dairy, eggs, citrus, tomato, chocolate

A: most parents requested transfer to another treatment within 1-2 months due to finding diet unsuccessful



McKendry 1975 (Continued)

and restricting

C: high dropout rate was due to parents refusing to allow their child to use the Mozes detector,

or finding it too expensive, or children fearing it especially if under age 8y

Data entered counting dropouts as failures (for above reasons)

Risk of bias



Moffatt 1987

Methods RCT (opaque envelopes)




Setting: Enuresis clinic, Montreal Children’s Hospital


No. of dropouts: A: 5

Incl: primary nocturnal enuresis, spoke English or French, 7 had daytime urgency (treated with retention

control training or anticholinergic drugs)

Ages: 8-14 years

Baseline wetting: 64% wet nights in each group

Interventions A (66): enuresis alarm + overlearning if successful

B (55): waiting list control

Duration of treatment mean (SD): A: 18.4 weeks (5.8), B: 13.2 weeks (1.9)


Adverse events: 4 of A could not cope with alarm method

Notes Groups comparable at baseline but A assessed later if likely to be successful

Children’s self-concept improved when they were successful

Risk of bias





Motavalli 1994

Methods RCT




Participants No. of children (boys): 29 (A: 6 B: 4 C: 4)

Incl: age 5 - 14; no organic causes; normal intelligence; wetting 2+ times a week; no treatment in previous

2 months

Mean age A: 9.1 years B: 9.2 C: 8.3

Baseline wetting: mean (SD) number of wet nights in 15 days: A: 9.1 (4.1) B: 11.2 (3.8) C: 10.9 (3.3)

Interventions A (10): imipramine - dose depended on age

B (9): clomipramine

C (10): alarm


Follow up: none

Outcomes Mean (SD) frequency of wetting during final two weeks of treatment

A: 4.1 (2.6) B: 6.6 (5.5) C: 2.8 (4.3)

Notes Turkish language

No significant difference between groups in terms of age or IQ

Not blinded

Unclear if intention to treat

Risk of bias



Nawaz 2002

Methods RCT (random allocation to groups following matching on age and sex)




Setting: community health centres in Glasgow, Scotland


Dropouts: 0

Incl: Age 7-12 years, baseline wetting at least twice per months, attending mainstream school and willing

to be randomised

Excl: medical, physiological or psychiatric pathology, diurnal enuresis, encopresis

Previous treatment: some, but stopped during trial

Age: Mean 9.9 years (SD 1.83)

Baseline wetting: mean 5.67 per week (SD 1.26) for 4 weeks



Nawaz 2002 (Continued)

Interventions A (12): DBT + alarm

B (12): alarm only

C (12): untreated controls continued recording wet nights for 16 weeks, then offered treatment they

preferred

A + B also received standardised instructions (manual and videotape) and had 2 weekly telephone calls

Duration of treatment: 16 weeks or until 14 dry nights if earlier

Follow up: 6 months

Outcomes Wet nights per week during trial (final week): A: mean 0.83 (SD 1.40), B: 3.25 (2.67), C: 5 (2.26)


No. relapsing after end of trial: A: 1, B: 1

Fail or relapse rate: A: 5/12, B: 10/12

Notes Groups comparable on age, sex, baseline wetting and DepCat (deprivation) scores

DBT described as: intensive first night, arousing child and taking him to toilet, accident contingencies

and normal routine

Risk of bias



Netley 1984

Methods RCT




Setting: Hospital for Sick Children Enuresis Clinic, Toronto


No. of dropouts: 27

Incl: primary nocturnal enuresis, age 6-12 years

Ages: mean A: 9 years, B: 10.7


B (31): Mozes detector (buzzer + electric shock to abdominal wall on wetting)

Duration of treatment unclear, ? till dry for 2 months

Outcomes Final outcome, after 2 dry months: A: 13/17 failed, B: 7/18 failed

Notes High dropout rate (44%)

Groups not comparable on age at baseline

Younger children (<8 years) apprehensive about detector

Authors conclude Mozes detector is suitable for children >8 years



Netley 1984 (Continued)

Risk of bias



Ng 2005

Methods RCT ’randomly allocated’ by consecutive sealed envelopes




Setting: Department of Pediatrics and Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital,

Hong Kong SAR, China

Participants Number of children 105

Dropouts: 12 (defaulted from treatment: A7, B2, C3; defaulted from follow up A2, B2, C5)

Inclusion: primary nocturnal enuresis

Exclusion: UTI in previous 3 months, daytime wetting, polyuric disorders, abnormal urinalysis, renal

disease, previous diuretics, unwilling to be randomised

Previous treatment: none (excluded if had desmopressin, alarms or tricyclics)

Age: range 7-12 years

Baseline wetting: at least 3 wet nights in baseline 2 weeks

Interventions A (35): alarm only (’Wet-Stop’ alarm)

B (38): oral desmopressin 200 µg, increased to 400 µg if > 1 wet night

C (32): both treatments


Follow up: 12 weeks

Outcomes Wet nights during trial (N, mean (SD)): A: 28, 2.8 (2.2), B: 36, 2.6 (2.4), C: 29, 1.3 (1.9)

Not achieving 14 dry nights: A: 27/35, B: 22/38, C: 12/32 (ITT, dropouts = failure)

Wet nights after trial (N, mean (SD)): A: 24, 2.5 (2.4), B: 34, 3.4 (2.5), C: 24, 2.6 (2.7)

Not achieving 14 dry nights or relapsing after: A: 25/35, B: 30/38, C: 19/32 (ITT, dropouts = failure)

Adverse effects: none

All children who responded completely to the alarm stayed dry afterwards

Notes All children had star charts and kept wetting diaries

Comparable at baseline on wetting frequency, age, gender, urine osmolality

More children failed to comply in Group A (alarm only), these were included as failures in the dry night

analyses

Risk of bias





Rodriguez 2001

Methods RCT (method not specified)




Setting: Hospital clinic, Spain

Participants No. of children: 84 (80% boys)

3 dropouts after 3 months

Incl: wetting at least 1x/week, age >7 years

Excl: diurnal enuresis, encopresis, neurological abnormalities

Previous treatment: 38% of children

Age range 7-14 years

Interventions A (30): bed alarm

B (29): alarm + desmopressin 20 µg or 40 µg for more frequent wetters (>2x/week)

Duration of treatment: 4-6 months

Outcomes Response: A: 73.3%; B: 58.6%

[=no. not achieving 14 dry nights: A: 8/30; B: 12/29]

All children treated with desmopressin if not cured at 6 months, therefore follow up not possible

Side effects: not reported

Notes Spanish language

No follow up

Risk of bias



Ronen 1992

Methods RCT (assigned chronologically in order of application)




Setting: children attending a community mental health clinic


Dropouts: 23 (A, 2; B, 4; C, 6; D, 11)

Incl: primary enuresis

Excl: medical or developmental problems; age <5 years


Baseline wetting: mean wet nights in 3 week (SD): A, 19.8 (1.73); B, 19.8 (2.14); C, 18.9 (2.21); D, 18

(8.72)



Ronen 1992 (Continued)

Interventions A (20): Cognitive + behavioural self-control education therapy counselling

B (19): enuresis alarm (bell and pad)

C (20): token economy (star chart + rewards)

D (18): control (waiting list for 3 months)


Follow up: at 6 months

Outcomes Cured (3 consecutive dry weeks): A, 15/20; B, 12/19; C, 6/20; D, 0/18

Failed (intention to treat, including dropouts as failures): A, 5/20; B, 7/19; C, 14/20; D, 18/18

No. of wet nights in 3 weeks at end of treatment: A, (18 children) mean 1.03, (SD2.15); B, (15) 1.23 (5.

28); C, (14) 3.33 (5.8); D, (16) 17.22 (9)

Actual failure or relapse after 6 months (excluding dropouts): A, 3/18; B, 9/15; C, 8/14


Notes A (cognitive treatment) had lowest dropout, highest success and lowest relapse compared with B, C or D

Risk of bias



Sacks 1974

Methods RCT (random but disproportionate allocation)




Participants No. of children: 83 (from previous study)

Excl: severe psychosis or organic causes

Ages: 5.5 to 14 years

Interventions A (64): conditioning (? alarm)

B (10): psychotherapy, counselling (12 weekly 40 min sessions + 20 min with mother)

C (9): Control

Duration of treatment: B 12 weeks

Outcomes No. not achieving 14 dry nights: A: 13/64, B: 8/10, C: 7/9

Notes Control group was older and had fewer boys

Risk of bias





Scholander 1968

Methods RCT (double-blind)





No dropouts

Previous treatment: all had received imipramine, amitriptyline or nortriptyline

Age range 7 to 17 years

Severity of wetting at baseline: wet bed between 2 and twelve times a week

Interventions Third week:

A (15): enuresis alarm + placebo

B (15): enuresis alarm + nortrityline 25-50 mg


FU after 6 to 12 months

Outcomes Number with no wet nights in third week (during drug/placebo treatment):

A: 3/15

B: 0/15

Number with no wet nights in fifth week (after drug/placebo treatment):

A: 6/15

B: 9/15

Side effects: 1 child frightened of the mattress, ’a few’ children on nortrityline had dry mouth or troubled

sleep

Notes Swedish language

No details of inclusion\exclusion criteria

Groups comparable in age and frequency of wet nights

Risk of bias



Sloop 1973

Methods Initially RCT

Subjects paired on IQ, sex, age and number of wet nights during baseline then one from each pair randomly

allocated to conditions




Setting: residential training centres for learning disabled children

Participants No. of children: 42 (boys: A: 11 B: 11)

Excl: epileptics; severe behaviour problems; encopretics;



Sloop 1973 (Continued)

residents in beds with side rails which prevent them arising; residents on nightly tranquilising medications;

measured IQ below 20; not wetting bed at least once during baseline

Previous treatment: none

Mean age: A: 13 years, B: 12 (range 7 to 18)

Baseline wetting: mean number of wet nights: Boys: A: 4.18 B: 4 Girls: A: 3.64 B: 3.54

Interventions A (21): enuresis alarm

B (21): control - usual “potting” procedure - taken to the toilet twice a night


Outcomes Number of wet nights in 7 weeks (boys, n=11) A: 46 B: 108

No significant difference for girls (no data)

Number (%) dry: A: 11/21 (52) B: 1/21 (5)

Number relapsed: A: 4/11 B: 0/1

Notes Males and females analysed separately

Not clear if intention to treat

One pair of boys switched after 3 nights of treatment

Risk of bias



Sukhai 1989 #

Methods RCT (double blind randomised cross-over with 2 weeks washout)




Participants No. of children: 28 (21 boys)

Dropouts: none

Incl: Normal urine concentration capacity of 800 mosmol/kg or higher; 3 or more wet nights per week

during observation period; informed parental consent; no urological or renal disorder; no history of

daytime wetting; no chronic urinary tract infection; no neurological or cardiovascular disease

Mean age: 11 years (range 7 to 16)

Previous treatment: 19 had previous attempts at treatment, including alarm (n=9) and tricyclic antide-

pressants (n=10)

Severity at baseline: mean (SEM) number of dry nights per week = 1.4 (0.3)

Interventions A: (28) enuresis alarm and bedtime dose of 20 µg DDAVP (desmopressin)

B: (28) enuresis alarm and bedtime dose of placebo

2 week washout period

Duration of treatment: 2 weeks in each arm

Follow up: 4 weeks to 6 months



Sukhai 1989 # (Continued)

Outcomes Mean (SEM) DRY nights during treatment: A: 5.1 (0.4) B: 4.1 (0.4)

6wk follow up: 14 dry, 5 relapsed

4.5 month follow up: 9 remained dry

Side effects: none reported

Mean urine osmolality significantly increased from baseline

Significantly higher urine osmolality with DDAVP than placebo

Steady significant increase in body weight

Notes Very good study

Risk of bias



Taylor 1975

Methods CCT - sequential allocation





No. of dropouts unclear because some replaced by next admission to enuresis clinic

Incl: aged between 4-16; parents saw enuresis as a problem; no relevant organic pathology


Age range 4 to 15 years: mean boys = 8.8; mean girls = 9.3

Daytime wetting: 16 children

Baseline wetting: no details

Severity of wetting at baseline: no details

number of dropouts unclear because some subjects replaced by next admission to enuresis clinic

Interventions A (21): continuous alarm - bed alarm triggered as soon as bed wet

B (18): alarm + intermittent reinforcement schedule - continuous alarm for 14 days then parents told

to switch alarm off whenever indicated by reinforcement schedule (50% of the time). Child unaware of

reinforcement schedule

C (22): alarm + overlearning - when patient achieved 7 consecutive dry nights, fluid intake increased by

1-2 pints prior to going to bed. This regime continued until success criterion achieved

Duration of treatment: Until success criterion met ie no more than 1 wetting incidence in 28 days

Follow up: after 3 m

Outcomes Number (%) achieving no more than one wetting incidence in 28 days: A: 13/21 (62) B: 9/18 (50) C:

13/22 (59)

Chi sq = 0.6 df = 2 not significant.

Number (%) of successes who relapsed A: 9/13 (69) B: 4/9 (44) C: 3/13 (23)

Chi sq = 5.6 df = 2 P=0.001



Taylor 1975 (Continued)

Notes Results from 61 participants analysed

Number of subjects at any given stage unclear

Probably atypical population due to referral process.

Comparability of groups at baseline not reported



Includes children with diurnal wetting (n=6), encopresis (n=10) and both (n=6)

Over-learning is initiated after successful alarm treatment (eg achievement of 14 consecutive dry nights).

Extra drinks are given at bed-time to cause additional stress to the detrusor muscles in the bladder. Alarm

treatment is then continued until 14 consecutive dry nights are again achieved

Risk of bias



Tobias 2001

Methods RCT (random numbers table)




Setting: urban paediatric medical centre


No. of dropouts: 7 lost to follow up or did not comply with treatment

Inclusion: primary or secondary enuresis, 3 wet nights of 7, age 6 to 12 years

Exclusion: Daytime wetting, chronic illness, UTI, urinary tract pathology

Previous treatment: yes but children asked to stop these while in trial


Interventions A (23): body worn audio alarm

B(24): body worn vibrating alarm

Duration of treatment: 90 nights or until 14 dry nights achieved

Follow up: none


Adverse events: some children did not wake, some were upset when woken, false alarm

Vibrating alarm was reported to be more uncomfortable than the audio alarm

Notes All children used star charts to record wet and dry nights but rewards for dry nights were not mentioned

Risk of bias




Tobias 2001 (Continued)


Turner 1970

Methods RCT (stratified by age (4-7 and 7-15) and sex (12:8 M:F))





Dropouts: 39 of 81 allocated to an alarm (A, B or C), due to failure to use equipment properly, disruption

or domestic problems. 1/32 from D or E

Incl: primary (103) and secondary (12) enuresis

Excl: organic pathology; adverse home conditions; bedwetting <3x/week; previous alarm treatment


Interventions A: (15) alarm, continuous signal

B: (15) alarm, twin signal

C: (12) Alarm, intermittent twin signal (after first 2 wks, alarm sometimes disconnected)

D: (15) random wakening

E: (17) Placebo tablet

Duration: 4 weeks for D and E only: if no success, withdrawn from study for alternative treatment)

Mean duration: A, 6.8 wk; B, 6.2 wk; C, 10.2 wks

Outcomes Failed at 4 weeks: A, 12/15; B, 13/15; D, 14/15; E, 13/17

Mean wet nights per week at 4 wks: A, 2.9 (SD 2.27); B, 3.58 (2.07); D, 3.23 (2.09); E, 4.22 (2.37)

Failure at end of treatment: A, 3/15; B, 4/15; C, 1/12

Longterm failure at 3 yrs: A+B combined, 13/20; C, 3/11

Adverse events: non-compliance, failure or family disruption caused high dropout rate

Notes Dropouts replaced by next child referred to the clinic. Some failures treated with methedrine. Trial unable

to reach required sample size of 20 children per group during 5 year recruitment period

Therefore unreliable trial and data not useable

Adverse events caused high dropout rate in alarm groups due to inability to use the equipment or family

disruption or strife

Risk of bias





van Londen 1993

Methods RCT (sequential random allocation in order of contact)




Setting: parents who contacted an alarm rental agency, Utrecht, Holland


No. of dropouts: 14 (A:3, B:2, C:9)

Incl: Primary (110) or secondary (17) enuresis

Ages: mean 8.6 y (range 6-12)

Interventions A (38): alarm + reward stickers for correct behaviour at the time (’arousal therapy’ = turning off alarm in

3 mins, going to bathroom to empty bladder, resetting alarm)

B (39): alarm + reward stickers in morning for dry bed and penalty (1 sticker) for wet bed

C (36): alarm only


FU at two and a half years

Outcomes No. not achieving 14 dry nights during trial: A:1/38, B:6/39, C:10/36

Failure + relapse rate during FU period: A: 11/38, B:21/39, C:10/36

Final failure + relapse rate at FU *: A:1/38, B:2/39, C:4/36

* but children who failed or relapsed received further treatment (repeat of trial arm, other alarm method,

desmopressin, imipramine, homeopathy, hospital referral, reduced drinking, regular ’wake-up’ alarm clock,

chiropractic, iriscopist, acupuncture, supervised child care) more often in B+C than A

Notes Groups comparable at baseline on age, gender, diagnosis and frequency of wetting

’Arousal therapy’ described as ’bibliotherapy’ beacuse parents received their instructions in written form

Risk of bias



Wagner 1982

Methods RCT




Setting: referrals from paediatric cinics, doctors, schools and newspaper advertisements


Dropouts: 13

Incl: age 6-16 years, IQ >70, primary nocturnal enuresis

Excl: daytime wetting, physical or neurological disorders, treatment with drugs or alarms in previous year

Ages: 6-16

Baseline wetting: min 3x/week, A: 75%, B: 77%, C: 64%



Wagner 1982 (Continued)

Interventions A (12): alarm (pad-and-bell /buzzer)

B (12): imipramine (if <32 kg, 25 mg/day, if >32 kg, 50 mg/day)

C (12): waiting list

Duration of treatment: 14 week or until dry for 14 nights

FU: max 44 days

Outcomes Per cent wet nights in 14th week: A: 8.25%, B: 39.25%, C: 60.83% (A significantly better than B or C)

No. not achieving 14 dry nights: A:2/12, B:8/12, C:11/12

No. not achieving 14 dry nights or relapsing: A: 7/12, B: 12/12, C:12/12

Time from cure to relapse: A: 37.8 days (range 25-44), B: 17 (3-27)

Notes Groups comparable on baseline wetting

No SDs or means

Risk of bias



Wagner 1985

Methods CCT (alternate allocation to groups)





No dropouts

Incl: between 5 and 16 years old; IQs not less than 70; no physical or neurologic disorders as assessed by

the child’s physician; wet the bed at least 3 nights a week before treatment; not had conditioning treatment

for at least a year; agreed to random assignment

Previous treatment: No details

Mean age: 7.9 years (range: 5 to 14)

Severity at baseline: % wet nights per week: A: 80 B: 83 C: 90

Interventions A (13): contiguous enuresis alarm

B (13): delayed response enuresis alarm - 3 second delay

C (13): waiting list control


Follow up: after 6 months

Outcomes Percentage of wet nights per week in week 12

A: 5.38 B: 20.67 C: 72.90

Number achieving 14 consecutive dry nights:

A: 8 B: 7 C: 1

Number relapsing

A: 2/8 B: 5/7 C: 1/1



Wagner 1985 (Continued)

Malfunction significantly greater problem for delayed alarm as compared with contiguous model

Notes Clinicians blind to specific purpose of the study

CCT rather than RCT

No significant differences in groups in terms of age, sex, recruitment source, psychological measures,

baseline wetting frequencies

No SDs or means

Contiguous alarm sounds as soon as wetting occurs

Delayed alarm sounds after a 3 second delay

Risk of bias



Werry 1965

Methods RCT (initial allocation by random numbers, in second half of trial stratified by age and sex)



Daytime wetting excluded: not mentioned

Setting: enuresis clinic, Paediatric Hospital, Montreal, Canada


No. of dropouts: 10 (A:1, B:4, C:5)

Incl: primary enuresis

Excl: dry more than 3 months, organic causes

Ages: mean 9.99 years (SD 2.5)

Baseline wetting: min 1 x/week (mean 5-6 x/week)

Interventions A (27): Control (no treatment for 4 m)

B (21): brief psychotherapy (6-8 sessions over 3 months)

C (22): alarms (bed buzzer) once per night

Duration of treatment: 3-4 months

Follow up: none

Outcomes Failure to achieve 14 dry nights (defined as no wet beds in preceding month): A: 26/27, B:19/21, C:15/

21

(C significantly better than A or B)

C (alarm) most economic as required least professional input

Notes Groups comparable on age, class, wetting severity and psychopathology

Majority of enuretic children were not emotionally disturbed (compared with, and found similar to, non-

enuretic siblings)

Risk of bias



Werry 1965 (Continued)



Wille 1986

Methods RCT




Distribution of social class of parents in 2 groups was similar

Dropouts not included in analysis


Incl: age over 6 years; not dry for more than 6 months (= ’primary enuresis’); at least 3 wet nights per

week at baseline; written informed parental consent

Excl: treatment for enuresis during previous year; daytime wetting; cardiovascular disease; renal disorder;

neurological disease; urinary tract infection

Age: over 6 years

Baseline wetting: mean number of dry nights per week: A:2.1, B:1.9

Number completing treatment: A:24, B:22

Interventions A (25): intranasal desmopressin (20 µg)

B (25): enuresis alarm


Failures crossed over to alternative, relapses continued on same treatment

Outcomes Mean (SEM) number of dry nights per week

In first week of treatment: A: 4.5 (0.4), B: 2.4 (0.4)

In 14th week: A: 4.9 (0.4), B: 5.9 (0.4)

No. failing during treatment (>5 wet nights in 28 or no change in enuresis score): A: 7/24, B: 3/22

A: 10 relapses given 3 months more desmopressin treatment. Successful for 7/10 but 4/7 relapsed imme-

diately and 1/7 after 2 months

B: 1 relapsed and further alarm treatment unsuccessful

No. not cured after treatment (failed or relapsed): A: 16/24, B: 4/22

Mean (SEM) dry nights after trial: A: 3.5 (0.4), B: 5.7 (0.4)

Side effects: A: nasal discomfort (5); nose bleeds (1); bad taste in throat (2); B: false alarms (21); alarm

did not go off (5); alarm did not wake child (15); other family members woken (15); child frightened by

alarm (1).

Lab tests: urine osmolality and density higher during treatment with desmopressin and urine osmolality

in alarm group lower during treatment than before

Notes Direct comparison of desmopressin and alarm

Results estimated from graph

Cure/relapse rates based on less strict definition of cure than usual

Risk of bias



Wille 1986 (Continued)



Wright 1974

Methods RCT

Medications on double blind basis





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


Follow up: 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 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

Data estimated from graph

No SDs

Risk of bias





Young 1972

Methods RCT (children chosen at random from children cured on alarm treatment)



Daytime wetting excluded: not mentioned

Setting: Local authority enuresis clinic, UK


Dropouts: A:6 B:37

Incl: primary and secondary nocturnal enuresis, age >4 years, already cured using alarm treatment

Ages: 4-15 years

Baseline wetting: min 2 wet nights per week before cure

Interventions A (61): alarm + overlearning

B (83): alarm alone (already cured)

Duration of treatment: 3 months or until relapse or cured again

Follow up: at 3 + 6 months, then 6-monthly till 2 years

Outcomes No. relapsing (failing to remain dry or regain dryness): A:7/55, B: 16/46

Notes A further 6 were withdrawn from A due to severe recurrence of enuresis with overlearning, but they then

regained dryness

Risk of bias



A = Alarm; Alarm = enuresis alarm triggered by wetting; cc = cubic centilitres; CCT = controlled clinical trial with quasi-randomised

method of allocation; Clock Alarm = clock set to ring at specified time after going to bed irrespective of wetting; CT = Cleanliness

Training (changing the bed); dB = decibels (measure of volume); DBT = Dry Bed Training (training night, CT, PP and W); Excl =

Exclusion criteria; FSHT = Full Spectrum Home Training (A + CT + Overlearning + Retention Control Training; Incl = Inclusion

criteria; IQ = intelligence quotient; No. = number; Overlearning = giving extra fluids at bedtime to child already cured using alarm

treatment; PP = Positive Practice (practising getting up and voiding repeatedly); Random Wakening = wakening the child to urinate

at random times; RCT = randomised controlled trial; Retention Control Training = increasing fluid intake and delaying urination

for increasing periods of time to expand bladder capacity; SD = Standard Deviation; SEM = standard error of the mean; Stream

interruption exercises = practising interruption of urination; UTI = urinary tract infection; Volume Alarm = alarm triggered by

ultrasound measurement of bladder volume, triggered at prespecified volume before wetting occurs; W = Waking (waking child to

void, earlier on subsequent nights if dry).



Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Azrin 1973 Excluded because participants were adults, and no useable data provided.

RCT: Yes

Comparison group: Yes


Systematic baseline measurement of wetting: Yes

Systematic outcome measure: Yes

Intervention: Alarms, dry bed training in adults with severe learning difficulties in a state hospital

Bollard 1977 RCT: No



Systematic baseline measurement of wetting: No


Intervention: Dry bed training

Bollard 1982b RCT: No





Intervention: Dry bed training with and without alarm + control group

Butler 2001 RCT: No

Comparison group: No

Intervention: Withdrawal from desmopressin or imipramine treatment, use of alarms optional

Collins 1973 RCT: No





Intervention: Pad-and-bell alarm, delayed alarm and no-treatment control group

Crisp 1984 RCT: Yes


Systematic Baseline: No

Systematic outcome measure: No


Intervention: Alarms vs wire mesh in adults

de Leon 1966 RCT: No




Systematic outcome measures: Yes

Interventions: Alarm (pad and buzzer), psychotherapy (counselling), no treatment control



(Continued)

Finley 1982 RCT: No





Interventions: Varying alarm schedules

Fordham 1989 RCT: No





Interventions: Alarms (bed based bell and pad, pants based sensor and mini-alarm)

Forsyth 1970 RCT: No





Interventions: Alarms

Freyman 1963 RCT: No






Gillison 1958 RCT: No






Goel 1984 RCT: No




Systematic outcome measures: No


Halliday 1987 RCT: Yes


Interventions: Pants alarm for daytime enuresis

Hansen 1995 RCT: No





(Continued)



Interventions: Alarms (pad and bell)

Hanson 1988 RCT: Yes but population young adults (age 13-29) with learning difficulties in residential centre





Interventions: Alarms, DBT, yoked awakening, rewards

Kahane 1955 RCT: No



Systematic baseline: No


Intervention: Alarms

Kaplan 1988 RCT: No





Interventions: Alarms, dry bed training, motivation

Kooijman 1986 RCT: No

Comparison group: Yes (from another study)




Intervention: Alarms with and without parental supervision

Kyneb 1975 RCT: No





Intervention: Alarms

Lovibond 1964d RCT: No





Intervention: Twin Signal alarm

McConaghy 1969 RCT: Yes





(Continued)



Interventions: Imipramine, amphetamine, alarms, behavioural method

Excluded because children moved between trial arms, data therefore unreliable

Monda 1995 RCT: No

Comparson group: Yes




Intervention: desmopressin, imipramine, alarms

Peterson 1969 RCT: No (unclear method, close group matching)



Systematic baseline: Yes


Interventions: Alarms (no delay, delay)

Philpott 1970 RCT: No





Interventions: Imipramine, alarms

Said 1991 RCT: No


Systematic baseline: Yes


Intervention: Alarms, overlearning

Shulz 1978 RCT: No

Comparison group: yes

Systematic baseline: no

Organic causes excluded: yes

Systematic outcome measure: yes

Intervention: DBT, alarms

Taylor 1963 RCT: No






Wickes 1958 RCT: No





(Continued)




Young 1965 RCT: No





Interventions: Central nervous system stimulants and conditioning (alarms)

DBT = Dry Bed Training (complex behavioural intervention)

Characteristics of ongoing studies [ordered by study ID]

Bryant 2002

Trial name or title Randomised trial of bladder training versus enuresis alarm versus combined bladder training/enuresis alarm

in children with nocturnal enuresis

Methods

Participants 106 children with nocturnal enuresis

Interventions Bladder training, alarms

Outcomes

Starting date 1st July 2001

Contact information Charmaine Bryant, Prince of Wales Hospital Sydney

Notes Recruitment finishes 30th June 2002



D A T A A N D A N A L Y S E S

Comparison 1. ALARM vs CONTROL

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Mean number of wet nights per

week

4 Mean Difference (IV, Fixed, 95% CI) Subtotals only

1.1 alarm vs control 4 109 Mean Difference (IV, Fixed, 95% CI) -3.34 [-4.14, -2.55]

1.2 delayed alarm vs control 1 36 Mean Difference (IV, Fixed, 95% CI) 0.13 [-1.16, 1.42]


week (no SDs)

Other data No numeric data

2.1 Alarm vs control Other data No numeric data

2.2 delayed alarm vs control Other data No numeric data

2.3 unsupervised alarm vs

control


3 Number not achieving 14

consecutive dry nights

16 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only

3.1 alarm vs control 14 576 Risk Ratio (M-H, Fixed, 95% CI) 0.39 [0.33, 0.45]

3.2 delayed alarm vs control 2 62 Risk Ratio (M-H, Fixed, 95% CI) 0.77 [0.62, 0.96]


control

1 30 Risk Ratio (M-H, Fixed, 95% CI) 0.42 [0.23, 0.76]

3.4 electric stimulation alarm

(Uristop) vs control


3.5 functioning electric

stimulation alarm (Uristop) vs

non-functioning alarm

1 53 Risk Ratio (M-H, Fixed, 95% CI) Not estimable

4 Numbers not achieving 14 dry

nights or relapsing


4.1 alarm vs control 5 162 Risk Ratio (M-H, Fixed, 95% CI) 0.57 [0.47, 0.70]

4.2 delayed alarm vs control 1 26 Risk Ratio (M-H, Fixed, 95% CI) 0.85 [0.65, 1.11]


control


Comparison 2. COMPARING ALARMS


studies

No. of



week

1 Mean Difference (IV, Fixed, 95% CI) Totals not selected

1.1 immediate alarm vs

delayed alarm

1 Mean Difference (IV, Fixed, 95% CI) Not estimable


week (no SDs)


2.1 bed alarm vs body alarm Other data No numeric data




delayed alarm


2.3 supervised alarm vs

unsupervised alarm


2.4 loud alarm vs quiet alarm Other data No numeric data

2.5 alarm with 105 dB bell +

light vs alarm with 78 dB bell

in parents’ room


2.6 alarm with intermittent

80 dB bell vs alarm with 78 dB

bell in parents’ room



nights


3.1 bed alarm vs body alarm 1 40 Risk Ratio (M-H, Fixed, 95% CI) 1.0 [0.39, 2.58]

3.2 continuous alarm vs

intermittent alarm



delayed alarm



unsupervised alarm


3.5 loud alarm vs quiet alarm 2 40 Risk Ratio (M-H, Fixed, 95% CI) 0.5 [0.19, 1.33]



in parents’ room






3.8 normal alarm vs twin

signal alarm


3.9 normal alarm vs electric

stimulation (Crosby Dri-nite)

alarm


3.10 body worn audio alarm

vs body worn vibrating alarm



nights or relapsing


4.1 bed alarm vs body alarm 1 40 Risk Ratio (M-H, Fixed, 95% CI) 1.11 [0.58, 2.14]

4.2 continuous alarm vs

intermittent alarm



delayed alarm



unsupervised alarm


4.5 loud alarm vs quiet alarm 2 40 Risk Ratio (M-H, Fixed, 95% CI) 1.1 [0.62, 1.96]



in parents’ room








4.8 normal alarm vs twin

signal alarm


4.9 normal alarm vs electric

stimulation (Crosby Dri-nite)

alarm


Comparison 3. ALARM vs BEHAVIOURAL INTERVENTIONS


studies

No. of



week


1.1 alarm vs star chart +

rewards


1.2 alarm vs stop-start training 1 Mean Difference (IV, Fixed, 95% CI) Not estimable


week (no SDs)


2.1 alarm vs random wakening Other data No numeric data


wake-up alarm clock


2.4 alarm vs dry bed training

(no alarm)



nights



rewards


3.2 alarm vs stop-start training 1 21 Risk Ratio (M-H, Fixed, 95% CI) 0.67 [0.35, 1.26]


(no alarm)


4 Mean number of wet nights at

follow-up


4.1 alarm vs stop-start training 1 Mean Difference (IV, Fixed, 95% CI) Not estimable


nights or relapsing

3 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

5.1 alarm vs waking / lifting 1 Risk Ratio (M-H, Fixed, 95% CI) Not estimable


rewards

1 Risk Ratio (M-H, Fixed, 95% CI) Not estimable


(no alarm)

1 Risk Ratio (M-H, Fixed, 95% CI) Not estimable



Comparison 4. ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS


studies

No. of



week


1.1 alarm vs alarm + retention

control training

2 40 Mean Difference (IV, Fixed, 95% CI) -0.04 [-0.70, 0.61]

1.2 alarm vs alarm + dry bed

training

2 43 Mean Difference (IV, Fixed, 95% CI) 1.00 [-0.20, 2.20]


week (no SDs)



supervised



control training



training


3 Number not achieving 14

consecutive dry nights



supervised



control training


3.3 alarm vs alarm +

overlearning + retention

control training


3.4 continuous alarm vs alarm

+ overlearning


3.5 intermittent alarm vs

alarm + overlearning



training


3.7 alarm vs alarm + dry

bed training SENSITIVITY

ANALYSIS


3.8 alarm vs alarm + reward

for correct behaviour at time of

wetting



for dry bed, penalty for wet bed


3.10 alarm + reward for

correct behaviour at time of

wetting vs alarm + reward for

dry bed, penalty for wet bed



nights or relapsing



supervised





control training



overlearning + retention

control training


4.4 continuous alarm vs alarm

+ overlearning


4.5 intermittent alarm vs

alarm + overlearning



training


4.7 alarm vs alarm + dry

bed training SENSITIVITY

ANALYSIS



for correct behaviour at time of

wetting



for dry bed, penalty for wet bed


4.10 alarm + reward for

correct behaviour at time of

wetting vs alarm + reward for

dry bed, penalty for wet bed



follow-up



training


Comparison 5. ALARM vs DRUGS


studies

No. of



week


1.1 alarm vs imipramine 1 20 Mean Difference (IV, Fixed, 95% CI) -0.65 [-2.21, 0.91]

1.2 alarm vs clomipramine 1 19 Mean Difference (IV, Fixed, 95% CI) -1.9 [-4.14, 0.34]

1.3 alarm vs desmopressin

(first week)

1 46 Mean Difference (IV, Fixed, 95% CI) 2.10 [0.99, 3.21]

1.4 alarm vs desmopressin

(last week)

2 110 Mean Difference (IV, Fixed, 95% CI) -0.41 [-1.20, 0.38]


desmopressin

3 324 Mean Difference (IV, Fixed, 95% CI) 0.77 [0.44, 1.09]

2 Mean number of wet nights

per week (no SDs or crossover

trials)


2.1 alarm vs placebo Other data No numeric data

2.2 alarm vs desmopressin Other data No numeric data




desmopressin


2.4 alarm vs imipramine Other data No numeric data


imipramine


2.6 alarm vs amphetamine

sulphate\Enetrol (ephedrine +

atropine)



nights during treatment

13 Risk Ratio (M-H, Random, 95% CI) Subtotals only

3.1 alarm vs placebo 1 122 Risk Ratio (M-H, Random, 95% CI) 0.68 [0.48, 0.97]

3.2 alarm vs desmopressin 4 316 Risk Ratio (M-H, Random, 95% CI) 0.85 [0.53, 1.37]


desmopressin

4 393 Risk Ratio (M-H, Random, 95% CI) 1.32 [0.80, 2.16]

3.4 alarm vs imipramine 3 208 Risk Ratio (M-H, Random, 95% CI) 0.59 [0.32, 1.09]

3.6 alarm + placebo vs alarm +

nortriptyline



methedrine


3.8 alarm vs amphetamine 1 33 Risk Ratio (M-H, Random, 95% CI) 0.46 [0.23, 0.89]

4 Number of wet nights at

follow-up (no SDs)


4.1 alarm vs placebo Other data No numeric data


desmopressin


4.3 alarm vs imipramine Other data No numeric data

4.4 alarm vs amitriptyline Other data No numeric data

5 Number not achieving 14 dry

nights or relapsing

7 Risk Ratio (M-H, Random, 95% CI) Subtotals only

5.1 alarm vs desmopressin 2 119 Risk Ratio (M-H, Random, 95% CI) 0.53 [0.14, 2.06]


desmopressin


5.3 alarm vs imipramine 1 24 Risk Ratio (M-H, Random, 95% CI) 0.6 [0.37, 0.97]

5.4 alarm + placebo vs alarm +

nortriptyline



follow-up

2 Mean Difference (IV, Random, 95% CI) Subtotals only

6.1 alarm vs desmopressin 2 104 Mean Difference (IV, Random, 95% CI) -1.59 [-2.86, -0.32]


desmopressin

1 48 Mean Difference (IV, Random, 95% CI) -0.10 [-1.55, 1.35]



Comparison 6. ALARM vs OTHER / MISCELLANEOUS TREATMENTS


studies

No. of



week


1.1 alarm vs cognitive therapy 1 Mean Difference (IV, Fixed, 95% CI) Not estimable


nights


3.1 alarm vs restricted diet 1 150 Risk Ratio (M-H, Fixed, 95% CI) 0.70 [0.60, 0.82]

3.2 alarm vs cognitive therapy

/ psychotherapy


4 Number not achieving 14 dry

nights or relapsing

1 Risk Ratio (M-H, Fixed, 95% CI) Totals not selected

4.1 alarm vs cognitive therapy 1 Risk Ratio (M-H, Fixed, 95% CI) Not estimable


week at follow up (no SDs)


5.1 alarm vs shaming Other data No numeric data

Analysis 1.1. Comparison 1 ALARM vs CONTROL, Outcome 1 Mean number of wet nights per week.

Review: Alarm interventions for nocturnal enuresis in children

Comparison: 1 ALARM vs CONTROL

Outcome: 1 Mean number of wet nights per week

Study or subgroup alarm augmented alarmMean

Difference WeightMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

1 alarm vs control

Bennett 1985 9 1 (1.95) 9 5.15 (1.5) 24.5 % -4.15 [ -5.76, -2.54 ]

Lynch 1984 18 1.69 (2.28) 18 4.06 (1.63) 37.8 % -2.37 [ -3.66, -1.08 ]

Nawaz 2002 12 3.25 (2.67) 12 5 (2.26) 16.2 % -1.75 [ -3.73, 0.23 ]

Ronen 1992 15 0.41 (1.76) 16 5.74 (3) 21.5 % -5.33 [ -7.05, -3.61 ]

Subtotal (95% CI) 54 55 100.0 % -3.34 [ -4.14, -2.55 ]

Heterogeneity: Chi2 = 10.76, df = 3 (P = 0.01); I2 =72%

Test for overall effect: Z = 8.23 (P < 0.00001)

2 delayed alarm vs control

Lynch 1984 18 4.19 (2.28) 18 4.06 (1.63) 100.0 % 0.13 [ -1.16, 1.42 ]

-10 -5 0 5 10

favours alarm favours control

(Continued . . . )



(. . . Continued)



Difference


Subtotal (95% CI) 18 18 100.0 % 0.13 [ -1.16, 1.42 ]

Heterogeneity: not applicable

Test for overall effect: Z = 0.20 (P = 0.84)

Test for subgroup differences: Chi2 = 20.04, df = 1 (P = 0.00), I2 =95%

-10 -5 0 5 10


Analysis 1.2. Comparison 1 ALARM vs CONTROL, Outcome 2 Mean number of wet nights per week (no

SDs).

Mean number of wet nights per week (no SDs)

Study Alarm Control

Alarm vs control

Baker 1969 1.8 wet nights, n=10 5.9 wet nights, n=10

Bollard 1981a 0.8 wet nights, n=15 4.6 wet nights, n=15

Bollard 1981b 0.6 wet nights (n=20) 4.4 wet nights (n=20)

Jehu 1977 0.3 wet nights, n=19 5.3 wet nights, n=20

Wagner 1982 0.58 wet nights, n=12 4.26 wet nights, n=12


delayed alarm vs control


unsupervised alarm vs control

Bollard 1981a 2.2 wet nights, n=15 4.6 wet nights, n=15



Analysis 1.3. Comparison 1 ALARM vs CONTROL, Outcome 3 Number not achieving 14 consecutive dry

nights.



Outcome: 3 Number not achieving 14 consecutive dry nights

Study or subgroup alarm control Risk Ratio Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

1 alarm vs control

Bennett 1985 5/9 9/9 0.58 [ 0.32, 1.03 ]

Bollard 1981a 3/15 15/15 0.23 [ 0.09, 0.57 ]

Bollard 1981b 4/20 18/20 0.22 [ 0.09, 0.54 ]

Houts 1986 3/12 11/11 0.28 [ 0.11, 0.69 ]

Jehu 1977 1/19 20/20 0.08 [ 0.02, 0.36 ]

Lynch 1984 11/18 18/18 0.62 [ 0.43, 0.90 ]

Moffatt 1987 19/61 54/55 0.32 [ 0.22, 0.46 ]

Nawaz 2002 9/12 11/12 0.82 [ 0.57, 1.18 ]

Ronen 1992 7/19 18/18 0.39 [ 0.22, 0.68 ]

Sacks 1974 13/64 7/9 0.26 [ 0.14, 0.47 ]

Sloop 1973 10/21 20/21 0.50 [ 0.32, 0.79 ]

Wagner 1982 2/12 11/12 0.18 [ 0.05, 0.65 ]

Wagner 1985 5/13 12/13 0.42 [ 0.21, 0.84 ]

Werry 1965 15/21 26/27 0.74 [ 0.56, 0.98 ]

Subtotal (95% CI) 316 260 0.39 [ 0.33, 0.45 ]

Total events: 107 (alarm), 250 (control)

Heterogeneity: Chi2 = 56.57, df = 13 (P<0.00001); I2 =77%



Lynch 1984 17/18 18/18 0.95 [ 0.81, 1.10 ]

Wagner 1985 6/13 12/13 0.50 [ 0.27, 0.92 ]

Subtotal (95% CI) 31 31 0.77 [ 0.62, 0.96 ]




3 unsupervised alarm vs control

Bollard 1981a 6/15 15/15 0.42 [ 0.23, 0.76 ]

Subtotal (95% CI) 15 15 0.42 [ 0.23, 0.76 ]

0.001 0.01 0.1 1 10 100 1000


(Continued . . . )



(. . . Continued)Study or subgroup alarm control Risk Ratio Risk Ratio





4 electric stimulation alarm (Uristop) vs control

Hojsgaard 1979 12/32 13/30 0.87 [ 0.47, 1.59 ]

Subtotal (95% CI) 32 30 0.87 [ 0.47, 1.59 ]




5 functioning electric stimulation alarm (Uristop) vs non-functioning alarm

Elinder 1985 0/36 0/17 0.0 [ 0.0, 0.0 ]

Subtotal (95% CI) 36 17 0.0 [ 0.0, 0.0 ]




0.001 0.01 0.1 1 10 100 1000




Analysis 1.4. Comparison 1 ALARM vs CONTROL, Outcome 4 Numbers not achieving 14 dry nights or

relapsing.



Outcome: 4 Numbers not achieving 14 dry nights or relapsing

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio


1 alarm vs control

Bollard 1981a 7/15 15/15 18.9 % 0.48 [ 0.29, 0.82 ]

Bollard 1981b 10/20 20/20 25.0 % 0.51 [ 0.33, 0.79 ]

Sloop 1973 14/21 20/21 24.4 % 0.70 [ 0.51, 0.96 ]

Wagner 1982 7/12 12/12 15.2 % 0.60 [ 0.37, 0.97 ]

Wagner 1985 7/13 13/13 16.5 % 0.56 [ 0.34, 0.91 ]

Subtotal (95% CI) 81 81 100.0 % 0.57 [ 0.47, 0.70 ]

Total events: 45 (Treatment), 80 (Control)

Heterogeneity: Chi2 = 2.23, df = 4 (P = 0.69); I2 =0.0%



Wagner 1985 11/13 13/13 100.0 % 0.85 [ 0.65, 1.11 ]

Subtotal (95% CI) 13 13 100.0 % 0.85 [ 0.65, 1.11 ]




3 unsupervised alarm vs control

Bollard 1981a 11/15 15/15 100.0 % 0.74 [ 0.54, 1.02 ]

Subtotal (95% CI) 15 15 100.0 % 0.74 [ 0.54, 1.02 ]




0.2 0.5 1 2 5




Analysis 2.1. Comparison 2 COMPARING ALARMS, Outcome 1 Mean number of wet nights per week.


Comparison: 2 COMPARING ALARMS



DifferenceMean

Difference


1 immediate alarm vs delayed alarm

Lynch 1984 18 1.69 (2.28) 18 4.19 (2.28) -2.50 [ -3.99, -1.01 ]

-4 -2 0 2 4

favours alarm 1 favours alarm 2

Analysis 2.2. Comparison 2 COMPARING ALARMS, Outcome 2 Mean number of wet nights per week (no

SDs).


Study Alarm 1 Alarm 2

bed alarm vs body alarm

Butler 1990a 1.2 wet nights, n=17 1 wet night, n=18

immediate alarm vs delayed alarm


supervised alarm vs unsupervised alarm

Bollard 1981a 0.8 with supervised alarm, n=15 2.2 with unsupervised alarm, n=15

loud alarm vs quiet alarm

Finley 1973 0.2 wet nights, n=10 0.6 wet nights, n=10

alarm with 105 dB bell + light vs alarm with 78 dB bell in parents’ room

Finley 1973 0.2 wet episodes, n=10 8 wet episodes, n=10

alarm with intermittent 80 dB bell vs alarm with 78 dB bell in parents’ room

Finley 1973 0.6 wet episodes, n=10 8 wet episodes, n=10



Analysis 2.3. Comparison 2 COMPARING ALARMS, Outcome 3 Numbers not achieving 14 dry nights.



Outcome: 3 Numbers not achieving 14 dry nights

Study or subgroup alarm 1 alarm 2 Risk Ratio Weight Risk Ratio


1 bed alarm vs body alarm

Butler 1990a 6/20 6/20 100.0 % 1.00 [ 0.39, 2.58 ]

Subtotal (95% CI) 20 20 100.0 % 1.00 [ 0.39, 2.58 ]

Total events: 6 (alarm 1), 6 (alarm 2)



2 continuous alarm vs intermittent alarm

Taylor 1975 8/21 9/18 100.0 % 0.76 [ 0.37, 1.56 ]

Subtotal (95% CI) 21 18 100.0 % 0.76 [ 0.37, 1.56 ]





Lynch 1984 11/18 17/18 73.9 % 0.65 [ 0.44, 0.95 ]

Wagner 1985 5/13 6/13 26.1 % 0.83 [ 0.34, 2.06 ]

Subtotal (95% CI) 31 31 100.0 % 0.70 [ 0.48, 1.01 ]




4 supervised alarm vs unsupervised alarm

Bollard 1981a 3/15 6/15 100.0 % 0.50 [ 0.15, 1.64 ]

Subtotal (95% CI) 15 15 100.0 % 0.50 [ 0.15, 1.64 ]




5 loud alarm vs quiet alarm

Finley 1973 1/10 2/10 25.0 % 0.50 [ 0.05, 4.67 ]

Finley 1977 3/10 6/10 75.0 % 0.50 [ 0.17, 1.46 ]

Subtotal (95% CI) 20 20 100.0 % 0.50 [ 0.19, 1.33 ]




6 alarm with 105 dB bell + light vs alarm with 78 dB bell in parents’ room

Finley 1973 1/10 10/10 100.0 % 0.14 [ 0.03, 0.64 ]

0.01 0.1 1 10 100


(Continued . . . )



(. . . Continued)Study or subgroup alarm 1 alarm 2 Risk Ratio Weight Risk Ratio


Subtotal (95% CI) 10 10 100.0 % 0.14 [ 0.03, 0.64 ]




7 alarm with intermittent 80 dB bell vs alarm with 78 dB bell in parents’ room

Finley 1973 2/10 10/10 100.0 % 0.24 [ 0.08, 0.71 ]

Subtotal (95% CI) 10 10 100.0 % 0.24 [ 0.08, 0.71 ]




8 normal alarm vs twin signal alarm

Lovibond 1964a 1/12 0/12 50.0 % 3.00 [ 0.13, 67.06 ]

Lovibond 1964c 2/12 0/12 50.0 % 5.00 [ 0.27, 94.34 ]

Subtotal (95% CI) 24 24 100.0 % 4.00 [ 0.48, 33.42 ]




9 normal alarm vs electric stimulation (Crosby Dri-nite) alarm

Lovibond 1964a 1/12 1/12 100.0 % 1.00 [ 0.07, 14.21 ]

Subtotal (95% CI) 12 12 100.0 % 1.00 [ 0.07, 14.21 ]




10 body worn audio alarm vs body worn vibrating alarm

Tobias 2001 10/23 14/24 100.0 % 0.75 [ 0.42, 1.33 ]

Subtotal (95% CI) 23 24 100.0 % 0.75 [ 0.42, 1.33 ]




0.01 0.1 1 10 100




Analysis 2.4. Comparison 2 COMPARING ALARMS, Outcome 4 Numbers not achieving 14 dry nights or

relapsing.






1 bed alarm vs body alarm

Butler 1990a 10/20 9/20 100.0 % 1.11 [ 0.58, 2.14 ]

Subtotal (95% CI) 20 20 100.0 % 1.11 [ 0.58, 2.14 ]




2 continuous alarm vs intermittent alarm

Taylor 1975 17/21 13/18 100.0 % 1.12 [ 0.79, 1.60 ]

Subtotal (95% CI) 21 18 100.0 % 1.12 [ 0.79, 1.60 ]





Wagner 1985 7/13 11/13 100.0 % 0.64 [ 0.37, 1.11 ]

Subtotal (95% CI) 13 13 100.0 % 0.64 [ 0.37, 1.11 ]




4 supervised alarm vs unsupervised alarm

Bollard 1981a 7/15 11/15 100.0 % 0.64 [ 0.34, 1.18 ]

Subtotal (95% CI) 15 15 100.0 % 0.64 [ 0.34, 1.18 ]




5 loud alarm vs quiet alarm

Finley 1973 5/10 3/10 30.0 % 1.67 [ 0.54, 5.17 ]

Finley 1977 6/10 7/10 70.0 % 0.86 [ 0.45, 1.64 ]

Subtotal (95% CI) 20 20 100.0 % 1.10 [ 0.62, 1.96 ]




6 alarm with 105 dB bell + light vs alarm with 78 dB bell in parents’ room

Finley 1973 5/10 10/10 100.0 % 0.52 [ 0.29, 0.96 ]

0.1 0.2 0.5 1 2 5 10


(Continued . . . )



(. . . Continued)Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio


Subtotal (95% CI) 10 10 100.0 % 0.52 [ 0.29, 0.96 ]




7 alarm with intermittent 80 dB bell vs alarm with 78 dB bell in parents’ room

Finley 1973 3/10 10/10 100.0 % 0.33 [ 0.14, 0.80 ]

Subtotal (95% CI) 10 10 100.0 % 0.33 [ 0.14, 0.80 ]




8 normal alarm vs twin signal alarm

Lovibond 1964a 5/12 5/12 50.0 % 1.00 [ 0.39, 2.58 ]

Lovibond 1964c 6/12 5/12 50.0 % 1.20 [ 0.50, 2.88 ]

Subtotal (95% CI) 24 24 100.0 % 1.10 [ 0.58, 2.09 ]




9 normal alarm vs electric stimulation (Crosby Dri-nite) alarm

Lovibond 1964a 5/12 6/12 100.0 % 0.83 [ 0.35, 2.00 ]

Subtotal (95% CI) 12 12 100.0 % 0.83 [ 0.35, 2.00 ]




0.1 0.2 0.5 1 2 5 10




Analysis 3.1. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 1 Mean number of

wet nights per week.


Comparison: 3 ALARM vs BEHAVIOURAL INTERVENTIONS



DifferenceMean

Difference


1 alarm vs star chart + rewards

Ronen 1992 15 0.41 (1.76) 14 1.11 (1.93) -0.70 [ -2.05, 0.65 ]

2 alarm vs stop-start training

Bennett 1985 9 1 (1.95) 12 3.25 (2.6) -2.25 [ -4.20, -0.30 ]

-10 -5 0 5 10

favours alarm favours behavioural


wet nights per week (no SDs).


Study Alarm Behavioural

alarm vs random wakening

Fournier 1987 2.5 wet nights, n=8 3.3 wet nights, n=8

alarm vs star chart + wake-up alarm clock

Baker 1969 1.8 wet nights, n=10 3.1 wet nights, n=10

alarm vs dry bed training (no alarm)

Azrin 1978 5.32 wet nights, n=27 1.05 wet nights, n=28

Bollard 1981b 0.6 wet nights, n=20 3.8 wet nights, n=20



Analysis 3.3. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 3 Numbers not

achieving 14 dry nights.




Study or subgroup alarm other behavioural Risk Ratio Weight Risk Ratio



Ronen 1992 7/19 14/20 100.0 % 0.53 [ 0.27, 1.01 ]

Subtotal (95% CI) 19 20 100.0 % 0.53 [ 0.27, 1.01 ]

Total events: 7 (alarm), 14 (other behavioural)




Bennett 1985 5/9 10/12 100.0 % 0.67 [ 0.35, 1.26 ]

Subtotal (95% CI) 9 12 100.0 % 0.67 [ 0.35, 1.26 ]




3 alarm vs dry bed training (no alarm)

Azrin 1978 23/27 0/27 2.4 % 47.00 [ 3.00, 736.47 ]

Bollard 1981b 4/20 15/20 71.4 % 0.27 [ 0.11, 0.66 ]

Caceres 1982 0/7 5/7 26.2 % 0.09 [ 0.01, 1.39 ]

Subtotal (95% CI) 54 54 100.0 % 1.33 [ 0.79, 2.24 ]




0.001 0.01 0.1 1 10 100 1000

favours alarm favours behaviour




wet nights at follow-up.



Outcome: 4 Mean number of wet nights at follow-up

Study or subgroup alarm behaviouralMean

DifferenceMean

Difference



Bennett 1985 9 0.85 (1.55) 12 3.45 (2.9) -2.60 [ -4.53, -0.67 ]

-10 -5 0 5 10

favours alarm favours behavioural

Analysis 3.5. Comparison 3 ALARM vs BEHAVIOURAL INTERVENTIONS, Outcome 5 Numbers not

achieving 14 dry nights or relapsing.




Study or subgroup alarm other behavioural Risk Ratio Risk Ratio


1 alarm vs waking / lifting

Lovibond 1964b 6/10 5/10 1.20 [ 0.54, 2.67 ]


Ronen 1992 9/15 8/14 1.05 [ 0.57, 1.94 ]

3 alarm vs dry bed training (no alarm)

Bollard 1981b 10/20 17/20 0.59 [ 0.37, 0.95 ]

0.1 0.2 0.5 1 2 5 10

favours alarm favours behaviour



Analysis 4.1. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 1 Mean

number of wet nights per week.


Comparison: 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS




Difference


1 alarm vs alarm + retention control training

Geffken 1986a 10 1.7 (1.2) 10 2.5 (0.9) 49.6 % -0.80 [ -1.73, 0.13 ]

Geffken 1986b 10 2.3 (1) 10 1.6 (1.1) 50.4 % 0.70 [ -0.22, 1.62 ]

Subtotal (95% CI) 20 20 100.0 % -0.04 [ -0.70, 0.61 ]



2 alarm vs alarm + dry bed training

Bennett 1985 9 1 (1.95) 10 1.4 (1.8) 50.4 % -0.40 [ -2.09, 1.29 ]

Nawaz 2002 12 3.25 (2.67) 12 0.83 (1.4) 49.6 % 2.42 [ 0.71, 4.13 ]

Subtotal (95% CI) 21 22 100.0 % 1.00 [ -0.20, 2.20 ]




-4 -2 0 2 4

favours alarm favours augmentation


number of wet nights per week (no SDs).


Study Alarm Augmented alarm

unsupervised alarm vs supervised

Bollard 1981a 2.2 wet nights with unsupervised alarm, n=15 0.8 with supervised alarm, n=15

alarm vs alarm + retention control training

Bollard 1982a 0.65 wet nights, n=12 (group B) 0.7 wet nights, n=12 (group E)

Fielding 1980 0.6 wet nights, n=17 1.5 wet nights, n=16

alarm vs alarm + dry bed training

Bollard 1981b 0.6 wet nights, n=20 0 wet nights, n=60



Mean number of wet nights per week (no SDs) (Continued)

Bollard 1982a 0.65 wet nights, n=12 (group B) 0.5 wet nights, n=12 (group F)

Butler 1988 1.81 wet nights, n=20 1.05 wet nights, n=29

Butler 1990b 1.6 wet nights, n=24 1.8 wet nights, n=24

Analysis 4.3. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 3 Number

not achieving 14 consecutive dry nights.



Outcome: 3 Number not achieving 14 consecutive dry nights

Study or subgroup alarm augmented alarm Risk Ratio Risk Ratio


1 unsupervised alarm vs supervised

Bollard 1981a 6/15 3/15 2.00 [ 0.61, 6.55 ]

Subtotal (95% CI) 15 15 2.00 [ 0.61, 6.55 ]

Total events: 6 (alarm), 3 (augmented alarm)




Bollard 1982a 0/12 0/12 0.0 [ 0.0, 0.0 ]

Fielding 1980 3/17 5/16 0.56 [ 0.16, 1.99 ]

Geffken 1986a 1/10 1/10 1.00 [ 0.07, 13.87 ]

Geffken 1986b 0/10 1/10 0.33 [ 0.02, 7.32 ]

Houts 1986 3/12 13/13 0.28 [ 0.11, 0.69 ]

Subtotal (95% CI) 61 61 0.39 [ 0.20, 0.77 ]




3 alarm vs alarm + overlearning + retention control training

Houts 1986 3/12 4/13 0.81 [ 0.23, 2.91 ]

Subtotal (95% CI) 12 13 0.81 [ 0.23, 2.91 ]



0.01 0.1 1 10 100

favours alarm favours augmented al

(Continued . . . )



(. . . Continued)Study or subgroup alarm augmented alarm Risk Ratio Risk Ratio



4 continuous alarm vs alarm + overlearning

Taylor 1975 8/21 9/22 0.93 [ 0.44, 1.95 ]

Subtotal (95% CI) 21 22 0.93 [ 0.44, 1.95 ]




5 intermittent alarm vs alarm + overlearning

Taylor 1975 9/18 9/22 1.22 [ 0.62, 2.42 ]

Subtotal (95% CI) 18 22 1.22 [ 0.62, 2.42 ]





Bennett 1985 5/9 5/10 1.11 [ 0.47, 2.60 ]

Bollard 1981b 4/20 0/60 26.14 [ 1.47, 465.41 ]

Butler 1988 8/28 10/35 1.00 [ 0.46, 2.19 ]

Butler 1990b 4/24 10/24 0.40 [ 0.15, 1.10 ]

Nawaz 2002 9/12 4/12 2.25 [ 0.95, 5.34 ]

Subtotal (95% CI) 93 141 1.21 [ 0.82, 1.81 ]




7 alarm vs alarm + dry bed training SENSITIVITY ANALYSIS

Bennett 1985 5/9 5/10 1.11 [ 0.47, 2.60 ]

Bollard 1981b 4/20 0/60 26.14 [ 1.47, 465.41 ]

Butler 1988 8/28 10/35 1.00 [ 0.46, 2.19 ]

Nawaz 2002 9/12 4/12 2.25 [ 0.95, 5.34 ]

Subtotal (95% CI) 69 117 1.67 [ 1.06, 2.62 ]




8 alarm vs alarm + reward for correct behaviour at time of wetting

van Londen 1993 10/36 1/38 10.56 [ 1.42, 78.34 ]

Subtotal (95% CI) 36 38 10.56 [ 1.42, 78.34 ]




9 alarm vs alarm + reward for dry bed, penalty for wet bed

van Londen 1993 10/36 6/39 1.81 [ 0.73, 4.46 ]

0.01 0.1 1 10 100


(Continued . . . )



(. . . Continued)Study or subgroup alarm augmented alarm Risk Ratio Risk Ratio


Subtotal (95% CI) 36 39 1.81 [ 0.73, 4.46 ]




10 alarm + reward for correct behaviour at time of wetting vs alarm + reward for dry bed, penalty for wet bed

van Londen 1993 1/38 6/39 0.17 [ 0.02, 1.35 ]

Subtotal (95% CI) 38 39 0.17 [ 0.02, 1.35 ]




0.01 0.1 1 10 100


Analysis 4.4. Comparison 4 ALARM vs ALARM + BEHAVIOURAL INTERVENTIONS, Outcome 4

Numbers not achieving 14 dry nights or relapsing.






1 unsupervised alarm vs supervised

Bollard 1981a 11/15 7/15 100.0 % 1.57 [ 0.84, 2.92 ]

Subtotal (95% CI) 15 15 100.0 % 1.57 [ 0.84, 2.92 ]





Fielding 1980 11/17 9/16 38.6 % 1.15 [ 0.66, 2.01 ]

Geffken 1986a 4/10 5/10 20.8 % 0.80 [ 0.30, 2.13 ]

Geffken 1986b 6/10 4/10 16.6 % 1.50 [ 0.60, 3.74 ]

Houts 1986 6/12 6/13 24.0 % 1.08 [ 0.48, 2.45 ]

Subtotal (95% CI) 49 49 100.0 % 1.12 [ 0.77, 1.64 ]


0.1 0.2 0.5 1 2 5 10


(Continued . . . )







3 alarm vs alarm + overlearning + retention control training

Houts 1986 6/12 5/13 100.0 % 1.30 [ 0.53, 3.17 ]

Subtotal (95% CI) 12 13 100.0 % 1.30 [ 0.53, 3.17 ]




4 continuous alarm vs alarm + overlearning

Taylor 1975 17/21 12/22 64.8 % 1.48 [ 0.96, 2.29 ]

Young 1972 16/46 7/55 35.2 % 2.73 [ 1.23, 6.07 ]

Subtotal (95% CI) 67 77 100.0 % 1.92 [ 1.27, 2.92 ]




5 intermittent alarm vs alarm + overlearning

Taylor 1975 13/18 12/22 100.0 % 1.32 [ 0.82, 2.13 ]

Subtotal (95% CI) 18 22 100.0 % 1.32 [ 0.82, 2.13 ]





Bollard 1981b 10/20 15/60 25.4 % 2.00 [ 1.08, 3.72 ]

Butler 1990b 13/24 17/24 57.6 % 0.76 [ 0.49, 1.20 ]

Nawaz 2002 10/12 5/12 16.9 % 2.00 [ 0.98, 4.09 ]

Subtotal (95% CI) 56 96 100.0 % 1.29 [ 0.94, 1.77 ]




7 alarm vs alarm + dry bed training SENSITIVITY ANALYSIS

Bollard 1981b 10/20 15/60 60.0 % 2.00 [ 1.08, 3.72 ]

Nawaz 2002 10/12 5/12 40.0 % 2.00 [ 0.98, 4.09 ]

Subtotal (95% CI) 32 72 100.0 % 2.00 [ 1.25, 3.20 ]




8 alarm vs alarm + reward for correct behaviour at time of wetting

van Londen 1993 10/36 11/38 100.0 % 0.96 [ 0.46, 1.98 ]

Subtotal (95% CI) 36 38 100.0 % 0.96 [ 0.46, 1.98 ]



0.1 0.2 0.5 1 2 5 10


(Continued . . . )






9 alarm vs alarm + reward for dry bed, penalty for wet bed

van Londen 1993 10/36 21/39 100.0 % 0.52 [ 0.28, 0.94 ]

Subtotal (95% CI) 36 39 100.0 % 0.52 [ 0.28, 0.94 ]




10 alarm + reward for correct behaviour at time of wetting vs alarm + reward for dry bed, penalty for wet bed

van Londen 1993 11/38 21/39 100.0 % 0.54 [ 0.30, 0.96 ]

Subtotal (95% CI) 38 39 100.0 % 0.54 [ 0.30, 0.96 ]




0.1 0.2 0.5 1 2 5 10



number of wet nights at follow-up.





DifferenceMean

Difference



Bennett 1985 9 0.85 (1.55) 10 2.35 (2.65) -1.50 [ -3.43, 0.43 ]

-4 -2 0 2 4




Analysis 5.1. Comparison 5 ALARM vs DRUGS, Outcome 1 Mean number of wet nights per week.


Comparison: 5 ALARM vs DRUGS


Study or subgroup Alarm DrugMean


Difference


1 alarm vs imipramine

Motavalli 1994 10 1.4 (2.15) 10 2.05 (1.3) 100.0 % -0.65 [ -2.21, 0.91 ]

Subtotal (95% CI) 10 10 100.0 % -0.65 [ -2.21, 0.91 ]



2 alarm vs clomipramine

Motavalli 1994 10 1.4 (2.15) 9 3.3 (2.75) 100.0 % -1.90 [ -4.14, 0.34 ]

Subtotal (95% CI) 10 9 100.0 % -1.90 [ -4.14, 0.34 ]



3 alarm vs desmopressin (first week)

Wille 1986 22 4.6 (1.88) 24 2.5 (1.96) 100.0 % 2.10 [ 0.99, 3.21 ]

Subtotal (95% CI) 22 24 100.0 % 2.10 [ 0.99, 3.21 ]



4 alarm vs desmopressin (last week)

Ng 2005 28 2.8 (2.2) 36 2.6 (2.4) 49.1 % 0.20 [ -0.93, 1.33 ]

Wille 1986 22 1.1 (1.88) 24 2.1 (1.96) 50.9 % -1.00 [ -2.11, 0.11 ]

Subtotal (95% CI) 50 60 100.0 % -0.41 [ -1.20, 0.38 ]



5 alarm vs alarm + desmopressin

Bradbury 1995 27 2.2 (2.12) 33 0.85 (1.61) 11.3 % 1.35 [ 0.38, 2.32 ]

Gibb 2004 106 2.4 (1.53) 101 1.8 (1.13) 79.5 % 0.60 [ 0.23, 0.97 ]

Ng 2005 28 2.8 (2.2) 29 1.3 (1.9) 9.3 % 1.50 [ 0.43, 2.57 ]

Subtotal (95% CI) 161 163 100.0 % 0.77 [ 0.44, 1.09 ]




-10 -5 0 5 10

favours alarm favours drug



Analysis 5.2. Comparison 5 ALARM vs DRUGS, Outcome 2 Mean number of wet nights per week (no SDs

or crossover trials).

Mean number of wet nights per week (no SDs or crossover trials)

Study Alarm Control / drug

alarm vs placebo

Fournier 1987 2.5 wet nights, n=8 5 wet nights, n=8

Kolvin 1972 2.3 wet nights, n=32 2.7 wet nights, n=27

Wright 1974 1.7 wet nights, n=10 3.5 wet nights, n=5

alarm vs desmopressin

Faraj 1999 0.7 wet nights, n=73 1.05 wet nights, n=62

alarm vs alarm + desmopressin

Leebeek 2001 3.9 wet nights, n=45 2.9 wet nights, n=47

Sukhai 1989 # 2.9 wet nights (SD 1.06) n=28 1.9 wet nights (SD 1.06) n=28

alarm vs imipramine

Fournier 1987 2.5 wet nights, n=8 1.9 wet nights, n=8



alarm vs alarm + imipramine

Fournier 1987 2.5 wet nights, n=8 1 wet night, n=8

alarm vs amphetamine sulphate\Enetrol (ephedrine + atropine)

Wright 1974 1.7 wet nights, n=10 4.1 wet nights, n=8



Analysis 5.3. Comparison 5 ALARM vs DRUGS, Outcome 3 Numbers not achieving 14 dry nights during

treatment.



Outcome: 3 Numbers not achieving 14 dry nights during treatment

Study or subgroup Alarm Drug Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 alarm vs placebo

Longstaffe 2000 26/61 38/61 100.0 % 0.68 [ 0.48, 0.97 ]

Subtotal (95% CI) 61 61 100.0 % 0.68 [ 0.48, 0.97 ]

Total events: 26 (Alarm), 38 (Drug)



2 alarm vs desmopressin

Faraj 1999 6/37 12/39 16.0 % 0.53 [ 0.22, 1.26 ]

Longstaffe 2000 26/61 31/60 35.7 % 0.82 [ 0.56, 1.21 ]

Ng 2005 27/35 22/38 38.6 % 1.33 [ 0.96, 1.85 ]

Wille 1986 3/22 7/24 9.7 % 0.47 [ 0.14, 1.59 ]

Subtotal (95% CI) 155 161 100.0 % 0.85 [ 0.53, 1.37 ]


Heterogeneity: Tau2 = 0.13; Chi2 = 8.45, df = 3 (P = 0.04); I2 =64%



Bradbury 1995 11/27 6/33 15.2 % 2.24 [ 0.95, 5.27 ]

Gibb 2004 55/106 49/101 38.4 % 1.07 [ 0.81, 1.40 ]

Ng 2005 27/35 12/32 28.0 % 2.06 [ 1.27, 3.33 ]

Rodriguez 2001 8/30 12/29 18.4 % 0.64 [ 0.31, 1.34 ]

Subtotal (95% CI) 198 195 100.0 % 1.32 [ 0.80, 2.16 ]





McKendry 1975 52/75 61/74 58.9 % 0.84 [ 0.70, 1.01 ]

Netley 1984 7/18 13/17 30.2 % 0.51 [ 0.27, 0.96 ]

Wagner 1982 2/12 8/12 10.9 % 0.25 [ 0.07, 0.94 ]

Subtotal (95% CI) 105 103 100.0 % 0.59 [ 0.32, 1.09 ]


0.01 0.1 1 10 100

favours alarm alone favours alarm + drug

(Continued . . . )



(. . . Continued)Study or subgroup Alarm Drug Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI



6 alarm + placebo vs alarm + nortriptyline

Scholander 1968 12/15 15/15 100.0 % 0.81 [ 0.61, 1.06 ]

Subtotal (95% CI) 15 15 100.0 % 0.81 [ 0.61, 1.06 ]




7 alarm vs alarm + methedrine

Kennedy 1968 4/10 0/8 100.0 % 7.36 [ 0.45, 119.38 ]

Subtotal (95% CI) 10 8 100.0 % 7.36 [ 0.45, 119.38 ]




8 alarm vs amphetamine

Forrester 1964 6/16 14/17 100.0 % 0.46 [ 0.23, 0.89 ]

Subtotal (95% CI) 16 17 100.0 % 0.46 [ 0.23, 0.89 ]




0.01 0.1 1 10 100

favours alarm alone favours alarm + drug

Analysis 5.4. Comparison 5 ALARM vs DRUGS, Outcome 4 Number of wet nights at follow-up (no SDs).

Number of wet nights at follow-up (no SDs)

Study Alarm Control / drug

alarm vs placebo


alarm vs alarm + desmopressin

Leebeek 2001 1.9 wet nights, n=37 2.7 wet nights, n=41

alarm vs imipramine


alarm vs amitriptyline



Number of wet nights at follow-up (no SDs) (Continued)

Danquah 1975 3.2 wet nights, n=10 4 wet nights, n=10

Analysis 5.5. Comparison 5 ALARM vs DRUGS, Outcome 5 Number not achieving 14 dry nights or

relapsing.



Outcome: 5 Number not achieving 14 dry nights or relapsing

Study or subgroup Alarm Drug Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI


Ng 2005 25/35 30/38 77.9 % 0.90 [ 0.69, 1.18 ]

Wille 1986 4/22 16/24 22.1 % 0.27 [ 0.11, 0.69 ]

Subtotal (95% CI) 57 62 100.0 % 0.53 [ 0.14, 2.06 ]





Bradbury 1995 14/27 10/33 16.0 % 1.71 [ 0.91, 3.22 ]

Gibb 2004 58/106 56/101 33.7 % 0.99 [ 0.77, 1.26 ]

Leebeek 2001 21/46 20/47 22.6 % 1.07 [ 0.68, 1.70 ]

Ng 2005 25/35 19/32 27.7 % 1.20 [ 0.84, 1.72 ]

Subtotal (95% CI) 214 213 100.0 % 1.10 [ 0.92, 1.31 ]


Heterogeneity: Tau2 = 0.0; Chi2 = 2.88, df = 3 (P = 0.41); I2 =0.0%



Wagner 1982 7/12 12/12 100.0 % 0.60 [ 0.37, 0.97 ]

Subtotal (95% CI) 12 12 100.0 % 0.60 [ 0.37, 0.97 ]




4 alarm + placebo vs alarm + nortriptyline

Scholander 1968 9/15 6/15 100.0 % 1.50 [ 0.71, 3.16 ]

0.001 0.01 0.1 1 10 100 1000


(Continued . . . )



(. . . Continued)Study or subgroup Alarm Drug Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Subtotal (95% CI) 15 15 100.0 % 1.50 [ 0.71, 3.16 ]




0.001 0.01 0.1 1 10 100 1000


Analysis 5.6. Comparison 5 ALARM vs DRUGS, Outcome 6 Mean number of wet nights at follow-up.




Study or subgroup Alarm DrugMean


Difference

N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI


Ng 2005 24 2.5 (2.4) 34 3.4 (2.5) 47.7 % -0.90 [ -2.18, 0.38 ]

Wille 1986 22 1.3 (1.88) 24 3.5 (1.96) 52.3 % -2.20 [ -3.31, -1.09 ]

Subtotal (95% CI) 46 58 100.0 % -1.59 [ -2.86, -0.32 ]




Ng 2005 24 2.5 (2.4) 24 2.6 (2.7) 100.0 % -0.10 [ -1.55, 1.35 ]

Subtotal (95% CI) 24 24 100.0 % -0.10 [ -1.55, 1.35 ]



-10 -5 0 5 10




Analysis 6.1. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 1 Mean

number of wet nights per week.


Comparison: 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS


Study or subgroup Alarm OtherMean

DifferenceMean

Difference


1 alarm vs cognitive therapy

Ronen 1992 15 0.41 (1.76) 18 0.34 (0.72) 0.07 [ -0.88, 1.02 ]

-4 -2 0 2 4

Favours alarm Favours other

Analysis 6.3. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 3 Numbers

not achieving 14 dry nights.




Study or subgroup Alarm Other Risk Ratio Weight Risk Ratio


1 alarm vs restricted diet

McKendry 1975 52/75 74/75 100.0 % 0.70 [ 0.60, 0.82 ]

Subtotal (95% CI) 75 75 100.0 % 0.70 [ 0.60, 0.82 ]

Total events: 52 (Alarm), 74 (Other)



2 alarm vs cognitive therapy / psychotherapy

Ronen 1992 7/19 5/20 12.9 % 1.47 [ 0.56, 3.85 ]

Sacks 1974 13/64 8/10 36.7 % 0.25 [ 0.14, 0.45 ]

Werry 1965 15/21 19/21 50.4 % 0.79 [ 0.58, 1.07 ]

Subtotal (95% CI) 104 51 100.0 % 0.68 [ 0.52, 0.90 ]

Total events: 35 (Alarm), 32 (Other)



0.1 0.2 0.5 1 2 5 10

favours alarm favours other



Analysis 6.4. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 4 Number

not achieving 14 dry nights or relapsing.



Outcome: 4 Number not achieving 14 dry nights or relapsing

Study or subgroup Alarm Other Risk Ratio Risk Ratio


1 alarm vs cognitive therapy

Ronen 1992 9/15 3/18 3.60 [ 1.18, 10.95 ]

0.1 0.2 0.5 1 2 5 10

favours alarm favours other

Analysis 6.5. Comparison 6 ALARM vs OTHER / MISCELLANEOUS TREATMENTS, Outcome 5 Mean

number of wet nights per week at follow up (no SDs).

Mean number of wet nights per week at follow up (no SDs)

Study Alarm Other

alarm vs shaming

Danquah 1975 3.2 wet nights, n=10 5.6 wet nights, n=10

W H A T ’ S N E W

Last assessed as up-to-date: 27 February 2007.

Date Event Description

20 August 2008 Amended Converted to new review format.

H I S T O R Y

Protocol first published: Issue 1, 2001

Review first published: Issue 1, 2001



Date Event Description

28 February 2007 New search has been performed Third (minor) update (Issue 3 2007), one new trial com-

paring desmopressin and alarms (Ng 2005) was added:

the review conclusion that children are less likely to re-

lapse after alarm treatment than after desmopressin were

not altered

22 February 2005 New citation required and conclusions have changed Substantive amendment. Second update Issue 2 2005.

Three new trials (Gibb 2004, Nawaz 2002 and Tobias

2001) were added. There was some evidence that dry

bed training may reduce the relapse rate

26 February 2003 New citation required and conclusions have changed Substantive amendment. First update Issue 2 2003.

Twelve trials which were previously included only in

a sensitivity analysis and 20 new trials were added.

Two previously included trials were excluded. Com-

pared to the previous version, there was more evidence

that alarms were better than no treatment, desmopressin

or tricyclics. Overlearning may reduce the relapse rate

C O N T R I B U T I O N S O F A U T H O R S

CMAG (the contact reviewer) originally based this review on work done at the NHS Centre for Reviews and Dissemination, University

of York, UK (see acknowledgements). CMAG used the data extracted by the York reviewers, converted them into Cochrane Review

format, and separated them into seven component intervention reviews (of which this is one).

This update includes 32 new trials. REP and CMAG performed double data abstraction for the new trials. All three reviewers edited

the text and JHCE also provided a clinical perspective and interpretation.

D E C L A R A T I O N S O F I N T E R E S T

JHCE has received reimbursement for attending a conference, fees for lecturing and a consultancy fee which was paid into a research

fund from Ferring Pharmaceuticals, manufacturers of desmopressin.

S O U R C E S O F S U P P O R T



Internal sources

• Chief Scientist Office, Scottish Executive Health Department, UK.

External sources

• National Health Service Research and Development Programme, UK.

I N D E X T E R M S

Medical Subject Headings (MeSH)

Absorbent Pads; Case-Control Studies; Deamino Arginine Vasopressin [therapeutic use]; Electrodes; Enuresis [drug therapy; ∗ prevention

& control]; Nephrology [methods]; Randomized Controlled Trials as Topic; Renal Agents [therapeutic use]

MeSH check words

Child; Child, Preschool; Humans



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