Nocturnal enuresis
(bedwetting beyond the age of five years)(1) is
fairly common in children; it reportedly affects
almost 20% of five-year old children, and up to 2%
of adolescents and young adults(2). Although a
reliable population-based estimate in Indian
children is not available, there is no reason to
suspect that the burden is insignificant. A single
cross-sectional, hospital-based study on sleep
disorders reported 18.4% prevalence of nocturnal
enuresis among 3-10y old children(3).
Relevance
In the absence of organic
disease, nocturnal enuresis can cause considerable
emotional trauma, embarrassment, guilt, reduced
quality of life, and stress- to the child and
family. Failure of spontaneous resolution compounds
the problem further.
The precise cause of nocturnal
enuresis is unclear. The significance of this lack
of clarity is that numerous interventions have been
tried to control, treat, or cure it, with variable
results. These include behavioural interventions,
mechanical devices, pharmacotherapy, complex
educational regimens and combinations of above. This
necessitates a detailed evaluation of current
evidence.
This overview of systematic
reviews is designed to identify which interventions
work, how they compare against each other and
whether combination of interventions is beneficial.
The specific question addressed is: In children with
nocturnal enuresis(population), what is the
impact of treatment with different modalities(intervention,
comparison) in terms of control/cure(outcome)?
Current Best Evidence
Literature search for Systematic
Reviews using the term "nocturnal enuresis"
was undertaken on 10 July 2010 in The Cochrane
Library(Filter: Record title) and
Medline(Limits: Meta-analysis, randomized
controlled trial, All child). The Cochrane
Library yielded 7 relevant Cochrane reviews, 1 other
systematic review and 188 methodologically appraised
clinical trials. Medline yielded 96 citations but no
additional new systematic reviews. Eight systematic
reviews are published till date(4-11). Searching for
randomized controlled trials beyond the search dates
in the respective systematic reviews yielded 16
potentially relevant citations, of which 7 were
relevant(12-18). However, none of these had data
that could be combined with the data in the
systematic reviews.
Seven(4-10) of the eight reviews
were authored by one group of Cochrane reviewers;
hence had uniform outcome measurements and high
methodological quality. The eighth review(11)
evaluated acupuncture, but owing to methodological
limitations is not considered in this Overview.
Outcomes were reported as symptom relief (defined as
mean reduction in number of wet nights per week),
treatment failure (relative risk of failure to
remain dry for 14 consecutive nights during
treatment), relapse during treatment (relative risk
of failure to remain dry after achieving 14
consecutive dry nights) and persistence/recurrence
of symptoms (mean difference in number of wet nights
after cessation of treatment). None of the reviews
described adverse effects of therapy, quality of
life and cost as outcomes.
As the objective of this Overview
was to identify the most efficacious intervention(s),
data from the reviews were extracted in the
following order: (i) intervention versus no
treatment or placebo to identify efficacious
interventions, (ii) efficacious interventions
of one type versus similar interventions, (iii)
efficacious interventions of one type versus
efficacious interventions of another type, and (iv)
combinations of interventions versus other
interventions, singly or in combination.
Table I-IV
(available as supplementary tables on
www.indianpediatrics.net) summarize the data.
The Overview revealed that the
following interventions are efficacious: (i)
simple behavioural interventions including retention
control training and cognitive/counselling
therapy(4), (ii) alarms(6), (iii)
desmopressin(7), (iv) tricyclic
antidepressants (imipramine, desipramine, viloxazine,
amitripty-line)(8), and (v) other drugs viz
indomethacin, diclofenac, diazepam, and
atomoxetine(9). Desmo-pressin is efficacious in
doses as low as 10mg/d; higher doses do not appear
to give greater benefit(7). The oral and nasal
routes appear to have comparable efficacy(7). No
specific type/mechanism of alarm appears to be
superior(6). Waking the child up(4), complex dry bed
training(5), and play with supportive therapy(10) do
not appear to be superior to placebo/nothing. Other
tricyclics and drugs not listed above are also not
efficacious(8,9).
Comparison of similar
interventions revealed that desmopressin is superior
to indomethacin and diclofenac(7), but similar to
amitriptyline or imipramine(8). Imipramine has
similar efficacy to viloxazine or clomipramine(8).
Retention control training is as efficacious as the
more complex dry bed training(5).
Alarms are superior to retention
control training(4), waking(4), dry bed training(5),
and cognitive/psychological/counselling therapy(10).
Their effect appears comparable to combination of
star chart with rewards(4). It is difficult to
establish whether alarms are superior (or inferior)
to desmopressin or imipramine(6). There is no added
efficacy when alarms are augmented with retention
control training(6), dry bed training(6), or
desmo-pressin(7). Desmopressin therapy is superior
to retention control training(4), and psychological
counselling(10). There is no benefit of augmenting
desmopressin with alarm, amitriptyline or
oxy-butinin(7). Amitriptyline is superior to
behavioural interventions(8). Limited data suggests
that acupuncture is superior to star chart(10).
Combinations of start chart with rewards or
lifting(4), imipramine and oxybutinin(8) combination
may be superior to monotherapy. However, no other
combinations are particularly efficacious. Fluid
restriction and avoidance of punishment could be
useful(5). Data were also utilized from the
additional RCTs(12-18).
Critical Appraisal
The complexity of the clinico-social
condition and its consequences for the child and
family, raise the following pertinent issues to
determine the most suitable approach in the local
context.
Is the significance of nocturnal
enuresis in Indian children similar to developed
countries? It is reported that majority of
Indian children co-sleep with parents(3), often till
early adolescence, despite the availability of
separate rooms/beds. This fact, coupled with
differences in sleep hygiene, make the relatively
benign condition disturbing for the whole family,
rather than individual child alone. Besides, the
logistics of arranging multiple sets of bedclothes,
linen, etc and manually washing/cleaning them, could
be more complex in our setting.
Should nocturnal enuresis be
treated? A number of children are likely to
recover/improve over time. The declining prevalence
till the mid-teens suggests an annual spontaneous
resolution rate of at least 10-15% among affected
children. Unfortunately, it is not possible to
predict this for an individual child. Therefore,
decision to intervene(or otherwise) has to be guided
by age of the child, assessment of the distress to
the child/ family, and practical issues in applying
one or more interventions.
Can interventions efficacious in
developed countries be applied here? The initial
approach to managing nocturnal enuresis
(conservative steps, avoiding punishment, managing
fluid intake/output appropriately, simple
behavioural interventions) can be practised with
adequate child and family motivation, patience and
understanding. More complex (and possibly expensive)
therapies including alarms, pharmacotherapy, and
combinations, require individualized decisions.
Do we need more research?
Barring desmopressin, alarms and some tricyclic
drugs, data is limited for most other interventions
in terms of quantity and/or quality. Further, some
of the older trials do not have the modern
methodological refinements to reduce bias. It would
be appropriate for our setting to evaluate not only
the efficacy of behavioural, device and
pharmacological interventions, but also their
effectiveness in terms of logistics, cost,
compliance, follow-up, social support, etc. This
would necessitate health technology assessment
research, rather than more individual trials.
Extendibility
There is paucity of research data
from developing countries, and almost none from
India. In addition, for the reasons cited above, it
may not be possible to directly extrapolate research
data on efficacy and expect similar effectiveness.
An appropriate evidence-based management solution
would be to discuss the efficacious options and
factor-in the opinions, perceptions and convenience
of the child/family (patient values) and
individualize treatment plans.
Conflict of interest: None
stated.
Funding: None.
References
1. WHO. Nonorganic enuresis. The
ICD-10 classification of mental and behavioural
disorders: Clinical descriptions and diagnostic
guidelines. Geneva: WHO, 1992.
2. Feehan M, McGee R, Stanton W,
Silva PA. A 6 year follow-up of childhood enuresis:
prevalence in adolescence and consequences for
mental health. J Paed Child Health 1990; 26: 75-79.
3. Bharti B, Malhi P, Kashyap S.
Patterns and Problems of Sleep in School Going
Children. Indian Pediatr 2006; 43: 35-38.
4. Glazener CMA, Evans JHC.
Simple behavioural and physical interventions for
nocturnal enuresis in children. Cochrane Database
Syst Rev 2004; 2: CD003637.
5. Glazener CMA, Evans JHC, Cheuk
DKL. Complementary and miscellaneous interventions
for nocturnal enuresis in children. Cochrane
Database Syst Rev 2005; 2: CD005230.
6. Glazener CMA, Evans JHC, Peto
RE. Alarm interventions for nocturnal enuresis in
children. Cochrane Database Syst Rev 2005; 2:
CD002911.
7. Glazener CMA, Evans JHC.
Desmopressin for nocturnal enuresis in children.
Cochrane Database Syst Rev 2002; 3: CD002112.
8. Glazener CMA, Evans JHC, Peto
RE. Tricyclic and related drugs for nocturnal
enuresis in children. Cochrane Database Syst Rev
2003; 3: CD002117.
9. Glazener CMA, Evans JHC, Peto
RE. Drugs for nocturnal enuresis in children (other
than desmopressin and tricyclics). Cochrane Database
Syst Rev 2003; 4: CD002238.
10. Glazener CMA, Evans JHC, Peto
RE. Complex behavioural and educational
interventions for nocturnal enuresis in children.
Cochrane Database Syst Rev 2004; 1: CD004668.
11. Bower WF, Diao M, Tang JL,
Yeung CK. Acupuncture for nocturnal enuresis in
children: a systematic review and exploration of
rationale. Neurourol Urodyn 2005; 24: 267-272
12. Chen YJ, Zhou GY, Jin JH.
Transcutaneous electrical acupoint stimulation
combined with auricular acupoint sticking for
treatment of primary nocturnal enuresis. Zhongguo
Zhen Jiu 2010; 30: 371-374 (abstract only).
13. Vogt M, Lehnert T, Till H,
Rolle U. Evaluation of different modes of combined
therapy in children with monosymptomatic nocturnal
enuresis. BJU Int 2010; 105: 1456-1459.
14. Van Kampen M, Lemkens H,
Deschamps A, Bogaert G, Geraerts I. Influence of
pelvic floor muscle exercises on full spectrum
therapy for nocturnal enuresis. J Urol 2009; 182 (4
Suppl): 2067-2071.
15. Gelotte CK, Prior MJ, Gu J. A
randomized, placebo-controlled, exploratory trial of
Ibuprofen and pseudoephedrine in the treatment of
primary nocturnal enuresis in children. Clin Pediatr
(Phila) 2009; 48: 410-419.
16. Ma J, Zhang YW, Wu H, Jiang
F, Jin XM. A randomized controlled clinical trial
for treatment of children with primary nocturnal
enuresis. Zhonghua Er Ke Za Zhi 2007; 45: 167-171.
17. Ferrara P, Marrone G,
Emmanuele V, Nicoletti A, Mastrangelo A, Tiberi E,
et al. Homotoxicological remedies versus
desmopressin versus placebo in the treatment of
enuresis: a randomised, double-blind, controlled
trial. Pediatr Nephrol 2008; 23: 269-274.
18. Sumner CR, Schuh KJ, Sutton VK, Lipetz R,
Kelsey DK. Placebo-controlled study of the effects
of atomoxetine on bladder control in children with
nocturnal enuresis. J Child Adolesc Psycho-pharmacol
2006; 16: 699-711.