What to Do if Desmopressin Doesn T Work

17 Treatment for children who do not respond to initial treatment with desmopressin and / or enuresis alarms for the management of bedwetting

17.1. Introduction

This section presents the evidence outlining which treatment should be considered when children have not responded to first line treatment. The question for the health care professional and patient is – should I continue with the treatment I have tried already or should I try an alternative treatment and if so what treatment should I use?

The evidence review indicated that multiple combinations of first line and second line treatments have been studied. Many children do not respond to first line treatment and the GDG were keen to understand the available evidence and how it might inform recommendations and practice. The tables below present the available evidence according to which treatment the child had not responded to and which treatment was used next.

The GDG considered from the direct evidence, the network meta-analsysis, the health economic evidence and their clinical experience that alarms or desmopressin were the first line treatments of choice. Tricyclic antidepressants did not emerge from the analyses as optimal first line treatments. Although studies examining treatment after non-response to tricyclic antidepressants were extracted and initially included in the evidence review details are not reported in this chapter as the GDG did not consider tricyclics should be used first line.

17.2. What is the clinical and cost effectiveness of additional treatment in children who have not responded to an adequate trial of desmopressin and / or enuresis alarms

17.2.1. Evidence review

Children who have not responded to ENURESIS ALARM therapy

17.2.1.1. Enuresis alarm compared to modified dry bed training (with an enuresis alarm) for children who have not responded to enuresis alarm therapy

Two randomised controlled trials, Butler (1988) ¹⁵¹ and Butler (1990) ¹¹², compared enuresis alarms to modified dry bed training with an enuresis alarm in children who have not responded to enuresis alarm treatment. Butler (1988) ¹⁵¹ and Butler (1990) ¹¹² described modified dry bed training as a waking schedule, retention control training, positive practice and cleanliness training but without any reprimands (adapted from Azrin (1974) ⁹²).

Table 17-1 Enuresis alarm compared to DBT for children who have not responded to enuresis alarms - Clinical summary of findings

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Outcome	Alarm	DBT	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	40/52 (76.9%)	29/59 (49.2%)	RR 1.52 (1.14 to 2.04)	256 more per 1000 (from 69 more to 512 more)	VERY LOW
Mean number of wet nights per week at the end of treatment (no SD)	52	59	-	not pooled	VERY LOW
Number of children who relapsed	17/48 (35.4%)	13/49 (26.5%)	RR 1.14 (0.63 to 2.07)	37 more per 1000 (from 98 fewer to 284 more)	VERY LOW
Number of children who dropped out	1/24 (4.2%)	2/24 (8.3%)	RR 0.5 (0.05 to 5.15)	42 fewer per 1000 (from 79 fewer to 344 more)	VERY LOW

17.2.1.2. Desmopressin compared to placebo for children who have not responded to enuresis alarm therapy

One randomised controlled trial Dimson (1996) ¹⁵² compared 20 micrograms intranasal desmopressin to placebo in children who had not responded to enuresis alarm treatment.

Table 17-2 Desmopressin compared to placebo for children who have not responded to enuresis alarms - Clinical summary of findings

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Outcome	Desmopressin	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	2/17 (11.8%)	0/17 (0%)	RR 5 (0.26 to 97)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Mean number of wet nights per week at the end of treatment (no SD)	17	17	-	not pooled	VERY LOW
Number of children who relapsed	2/2 (100%)	0/0 (0%)	not pooled	not pooled	LOW

Children who have not responded to DESMOPRESSIN

17.2.1.3. Enuresis alarm and placebo compared to enuresis alarm and desmopressin for children who have not responded to desmopressin therapy

One randomised controlled trial, Gibb (2003) ¹⁵³, compared enuresis alarm and placebo to enuresis alarm with 20 – 40 micrograms intranasal desmopressin in children who had not responded to desmopressin.

Table 17-3 Enuresis alarm and placebo compared to enuresis alarm and desmopressin for children who have not responded to enuresis alarm or desmopressin - Clinical summary of findings

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Outcome	Alarm and placebo	Alarm and desmopressin	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 28 consecutive dry nights	51/106 (48.1%)	52/101 (51.5%)	RR 0.93 (0.71 to 1.23)	36 fewer per 1000 (from 149 fewer to 118 more)	VERY LOW
Mean number of wet nights per week at the end of treatment	106	101	-	MD 0.6 (0.23 to 0.97)	VERY LOW
Number of children who dropped out	17/106 (16%)	9/101 (8.9%)	RR 1.8 (0.84 to 3.85)	71 more per 1000 (from 14 fewer to 254 more)	VERY LOW

Children who have not responded to desmopressin, imipramine or oxybutynin therapy

17.2.1.4. Acupuncture for children who had not responded to desmopressin, imipramine or oxybutynin

One observational study Serel (2001) ¹⁵⁴ considered acupuncture for children who had not responded to treatment with desmopressin, imipramine or oxybutynin. The study was identified in the update search.

Children with severe wetting resistant to ENURESIS ALARM therapy

17.2.1.5. Desmopressin compared to placebo for children with severe wetting resistant to enuresis alarm therapy

One randomised controlled trial Terho (1991) ¹⁵⁵ compared 20 to 40 micrograms intranasal desmopressin to placebo in children who had not responded to enuresis alarm treatment.

Table 17-4 Desmopressin compared to placebo for children with severe wetting resistant to enuresis alarms - Clinical summary of findings

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Outcome	Desmopressin	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Mean number of wet nights per week at the end of treatment (no SD)	26	26	-	not pooled	LOW

Children who have not responded to ENURESIS ALARM therapy or DESMOPRESSIN

17.2.1.6. Desmopressin compared to placebo for children with bedwetting for children who have not responded to enuresis alarm or desmopressin therapy

Two randomised controlled trials, Fjellestad (1987) ¹⁵⁶ and Stenberg (1994) ¹⁵⁷ compared desmopressin to placebo for children who have not responded to enuresis alarms or desmopressin. Fjellestad (1987) ¹⁵⁶ considered 200 micrograms tablet and 20 micrograms intranasal desmopressin to placebo and Stenberg (1994) ¹⁵⁷ considered 200 to 400 micrograms tablet desmopressin to placebo.

Table 17-5 Desmopressin tablets compared to placebo for children with bedwetting who have not responded to enuresis alarms or desmopressin - Clinical summary of findings

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Outcome	Desmopressin tablets	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	2/30 (6.7%)	0/30 (0%)	RR 5 (0.25 to 99.95)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Mean number of wet nights per week at the end of treatment	10	10	-	MD −2.3 (−3.57 to − 1.03)	LOW
Mean number of wet nights per week at the end of treatment (no SD)	30	30	-	not pooled	VERY LOW

Table 17-6 Desmopressin spray compared to placebo for children with bedwetting resistant to enuresis alarms or desmopressin - Clinical summary of findings

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Outcome	Desmopressin spray	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	1/30 (3.3%)	0/30 (0%)	RR 3 (0.13 to 70.83)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Mean number of wet nights per week at the end of treatment (no SD)	30	30	-	not pooled	VERY LOW

17.2.1.7. Tablet desmopressin compared to intranasal desmopressin for children with bedwetting, who have not responded to enuresis alarm or desmopressin therapy

One randomised controlled trial Fjellestad (1987) ¹⁵⁶ compared 200 micrograms tablet desmopressin to 20 micrograms intranasal desmopressin for children who have not responded to enuresis alarms or desmopressin.

Table 17-7 Tablet desmopressin compared to intranasal desmopressin for children with bedwetting who have not responded to enuresis alarms or desmopressin - Clinical summary of findings

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Outcome	Tablet desmopressin	Intranasal desmopressin	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	2/30 (6.7%)	1/30 (3.3%)	RR 2 (0.19 to 20.9)	33 more per 1000 (from 27 fewer to 657 more)	VERY LOW
Mean number of wet nights per week at the end of treatment (no SD)	30	30	-	not pooled	VERY LOW

Children who have not responded to ENURESIS ALARM therapy and DESMOPRESSIN

17.2.1.8. Imipramine compared to placebo for children with bedwetting, who have not responded to enuresis alarm and desmopressin therapy

One randomised controlled trial Neveus (2008) ¹⁵⁸ compared 25 to 50mg imipramine to placebo for children who have not responded to enuresis alarms and desmopressin.

Table 17-8 Imipramine compared to placebo for children with bedwetting who have not responded to enuresis alarms and desmopressin - Clinical summary of findings

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Outcome	Imipramine	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	5/25 (20%)	0/25 (0%)	RR 11 (0.64 to 188.95)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Number of children who achieved >50% improvement	2/25 (8%)	0/25 (0%)	RR 5 (0.25 to 99.16)	0 more per 1000 (from 0 fewer to 0 more)	LOW
Mean number of wet nights in the last 2 weeks of treatment	25	25	-	MD −3.2 (−5.72 to − 0.68)	LOW
Number of children who dropped out	1/25 (4%)	1/25 (4%)	RR 1 (0.07 to 15.12)	0 fewer per 1000 (from 37 fewer to 565 more)	LOW

17.2.1.9. Imipramine compared to tolterodine for children with bedwetting, who have not responded to enuresis alarm and desmopressin therapy

One randomised controlled trial Neveus (2008) ¹⁵⁸ compared 25 to 50mg imipramine to 1 to 2 mg tolterodine for children who have not responded to enuresis alarms and desmopressin.

Table 17-9 Imipramine compared to tolterodine for children with bedwetting who have not responded to enuresis alarms and desmopressin - Clinical summary of findings

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Outcome	Imipramine	Tolterodine	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	5/25 (20%)	0/25 (0%)	RR 11 (0.64 to 188.95)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Number of children who achieved >50% improvement	2/25 (8%)	1/25 (4%)	RR 2 (0.19 to 20.67)	40 more per 1000 (from 32 fewer to 787 more)	LOW
Mean number of wet nights in the last 2 weeks of treatment	25	25	-	MD −2.6 (−5.12 to − 0.08)	LOW
Number of children who dropped out	1/25 (4%)	0/25 (0%)	RR 3 (0.13 to 70.3)	0 more per 1000 (from 0 fewer to 0 more)	LOW

17.2.1.10. Tolterodine compared to placebo for children with bedwetting who have not responded to enuresis alarm and desmopressin therapy

One randomised controlled trial Neveus (2008) ¹⁵⁸ compared 1 to 2 mg tolterodine to placebo for children who have not responded to enuresis alarms and desmopressin.

Table 17-10 Tolterodine compared to placebo for children with bedwetting who have not responded to enuresis alarms and desmopressin - Clinical summary of findings

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Outcome	Tolterodine	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	0/25 (0%)	0/25 (0%)	not pooled	not pooled	MODERATE
Number of children who achieved >50% improvement	1/25 (4%)	0/25 (0%)	RR 3 (0.13 to 70.3)	0 more per 1000 (from 0 fewer to 0 more)	LOW
Mean number of wet nights in the last 2 weeks of treatment	25	25	-	MD −0.6 (−2.76 to 1.56)	LOW
Number of children who dropped out	0/25 (0%)	1/25 (4%)	RR 0.33 (0.01 to 7.81)	27 fewer per 1000 (from 40 fewer to 272 more)	LOW

Children with severe wetting resistant to DESMOPRESSIN

17.2.1.11. Desmopressin treatment after not responding to previous desmopressin treatment for children with severe bedwetting

One observational study Wikstrom (1996), ¹⁵⁹ considered desmopressin treatment for children who had not responded to 3 sets of treatment including the final treatment being desmopressin. Children were given 20 to 40 micrograms of intranasal desmopressin at bedtime for 4 to 6 weeks. If patients responded, the treatment was continued for 3 months using the dose the child responded at. If the child still dry after 3 months the treatment was continued for 3 to 6 months, but gradually reduced in dosage to 10 micrograms until the child was dry for 3 to 6 months. If there was no response to desmopressin after 4 to 6 weeks, children who had partially responded were given an enuresis alarm as well for 12 weeks, those who had not responded were taken off desmopressin and given an enuresis alarm instead for 12 weeks. In some children who failed to respond, treatment was stopped for 6 to 9 months and then started again.

Children with monosymptomatic nocturnal enuresis not responding to alarm therapy

17.2.1.12. Alarm and desmopressin for children with monosymptomatic nocturnal enuresis who have not responded to alarm therapy

One observational study, Vogt (2009) ¹⁶⁰ considered alarms combined with desmopressin for children who do not respond to 3 months of alarm treatment. The study outcomes were the number of children who became dry (defined as a maximum of 2 wet nights per month) and the number of children who relapsed after 1 year. Children had a mean age of 10.05 years and had 3 months of treatment. The study showed 11 out of 14 children became dry and after 1 year no children had relapsed when treated with alarm and desmopressin.

Children with monosymptomatic nocturnal enuresis not responding to desmopressin therapy

17.2.1.13. Desmopressin and placebo compared to desmopressin and tolterodine placebo for children with monosymptomatic nocturnal enuresis for children who have not responded to desmopressin therapy

One randomised controlled trial Austin (2008) ¹⁶¹ compared 600 micrograms desmopressin and placebo to 600 micrograms desmopressin and 4 mg tolterodine for children who have not responded to desmopressin.

Table 17-11 Desmopressin and placebo compared to desmopressin and tolterodine for monosymptomatic children who have not responded to desmopressin - Clinical summary of findings

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Outcome	Desmopressin and placebo	Desmopressin and tolterodine	Relative risk (95% CI)	Absolute effect	Quality
Number of children who achieved 14 consecutive dry nights	1/16 (6.3%)	3/18 (16.7%)	RR 0.38 (0.04 to 3.25)	104 fewer per 1000 (from 160 fewer to 376 more)	LOW
Number of children who achieved 50% improvement	4/16 (25%)	5/18 (27.8%)	RR 0.9 (0.29 to 2.78)	28 fewer per 1000 (from 197 fewer to 495 more)	LOW

17.2.1.14. Enuresis alarm treatment after not responding to desmopressin treatment in children with monosymptomatic nocturnal enuresis

One observational study Tuygun (2007) ¹¹⁶ compared desmopressin (20 to 40 micro grams intranasal desmopressin or 200 micrograms to 400 micrograms tablet desmopressin) to enuresis alarms, in the second part of the trial those who had failed to respond to desmopressin were entered into a third treatment group of enuresis alarm. The study outcomes were the number of children who achieved a greater than 90% reduction in the number of wet nights, the number of children who had a 50 to 90% reduction in the number of wet nights, the mean number of wet nights in the final month of treatment and the number of children who relapsed at 6 months. The median age of children was 8 years and each had 3 months of treatment. In the group of children treated with enuresis alarm after failing desmopressin treatment the trial showed 13 out of 19 (68.42%) achieved a >90% decrease in number of wet nights; 3 out of 19 (15.78%) achieved 50 to 90% reduction in the number of wet nights; at 6 months 6 out of 9 (31.57%) had relapsed; the mean number of wet nights per week at the end of treatment was 5.5 (SD 10.65).

These results can be compared to enuresis alarm therapy as first line treatment; the trial showed in the enuresis alarm as second line treatment group 13 out of 19 (68.42%) achieved a >90% decrease in number of wet nights, this was compared to 20 out of 35 children (57.14%) who had enuresis alarm treatment as first line therapy. 3 out of 19 (15.78%) children in the enuresis alarm as second line treatment group achieved 50 to 90% reduction in the number of wet nights compared to 9 out of 35 (27.71%) children in enuresis alarm treatment as first line therapy group. After 6 months, 6 out of 9 (31.57%) of children in the enuresis alarm as second line treatment had relapsed compared to 10 out of 35 children (28.57%) in the enuresis alarm as first line therapy group. None of these differences were significant. In the enuresis alarm as second line treatment the mean number of wet nights per week at the end of treatment was 5.5 (SD 10.65), compared to 23.2 (SD 6.23) in the enuresis alarm as first line treatment. The difference in mean number of wet nights was significant.

17.2.1.15. Desmopressin and alarm for children with monosymptomatic nocturnal enuresis for children who have not responded to desmopressin therapy

One observational study, Vogt (2009) ¹⁶⁰ considered desmopressin combined with alarm for children who are treatment resistant to 3 months of desmopressin treatment. The study considered children with monosymptomatic nocturnal enuresis. The study outcomes were the number of children who became dry (defined as a maximum of 2 wet nights per month) and the number of children who relapsed after 1 year. Children had a mean age of 10.05 years and had 3 months of treatment. The study showed 11 out of 14 children became dry and after 1 year no children had relapsed when treated with alarm and desmopressin.

17.2.1.16. Desmopressin and oxybutynin for children with monosymptomatic nocturnal enuresis who are non responders to desmopressin

One observational study, Radvanska (2006) ¹⁶² considered desmopressin combined with oxybutynin for children with monosymptomatic nocturnal enuresis. Radvanska (2006) ¹⁶² considered children who were non-responders (less than 50% improvement) to a 2 week trial of 20 micrograms intranasal desmopressin. Children had 20 micrograms intranasal desmopressin and 5 mg oxybutynin twice daily.

Side effects of second line treatments

17.2.1.17. Enuresis alarm with desmopressin compared to enuresis alarm with placebo for children treatment resistant to desmopressin

One randomised controlled trial, Gibb (2004) ¹⁵³ compared enuresis alarm with desmopressin to enuresis alarm with placebo.

Table 17-12 Enuresis alarm and desmopressin compared to enuresis alarm and placebo- Clinical summary of findings

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Outcome	Alarm and desmopressin	Alarm and placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children with headaches	1/101 (1%)	0/106 (0%)	RR 3.15 (0.13 to 76.37)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW

17.2.1.18. Desmopressin compared to placebo for children treatment resistant to enuresis alarms with severe bedwetting

One randomised controlled trial, Stenberg (1994) ¹⁵⁷, compared desmopressin to placebo.

Table 17-13 Desmopressin compared to placebo - Clinical summary of findings

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Outcome	Desmopressin	Placebo	Relative risk (95% CI)	Absolute effect	Quality
Number of children with headaches	5/10 (50%)	0/10 (0%)	RR 11 (0.69 to 175.86)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Number of children with abdominal pain	6/10 (60%)	0/10 (0%)	RR 13 (0.83 to 203.83)	0 more per 1000 (from 0 fewer to 0 more)	VERY LOW
Number of children with nausea and vertigo	1/10 (10%)	0/10 (0%)	RR 3 (0.14 to 65.9)	0 more per 1000 (from 0 fewer to 0 more)	LOW

17.2.1.19. Imipramine compared to tolterodine for children treatment resistant to enuresis alarms and desmopressin

One randomised controlled trial, Neveus (2008) ¹⁵⁸ considered imipramine compared to tolterodine.

Table 17-14 Imipramine compared to tolterodine - Clinical summary of findings

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Outcome	Imipramine	Tolterodine	Relative risk (95% CI)	Absolute effect	Quality
Number of children with slight mood change	3/27 (11.1%)	1/27 (3.7%)	RR 3 (0.33 to 27.06)	74 more per 1000 (from 25 fewer to 964 more)	LOW
Number of children with insomnia	2/27 (7.4%)	0/27 (0%)	RR 5 (0.25 to 99.51)	0 more per 1000 (from 0 fewer to 0 more)	LOW
Number of children with palpitations	1/27 (3.7%)	0/27 (0%)	RR 3 (0.13 to 70.53)	0 more per 1000 (from 0 fewer to 0 more)	LOW
Number of children with slight nausea	2/27 (7.4%)	0/27 (0%)	RR 5 (0.25 to 99.51)	0 more per 1000 (from 0 fewer to 0 more)	LOW

17.2.1.20. Tolterodine compared to imipramine for children treatment resistant to enuresis alarms and desmopressin

One randomised controlled trial, Neveus (2008) ¹⁵⁸ considered tolterodine compared to imipramine.

Table 17-15 Tolterodine compared to imipramine - Clinical summary of findings

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Outcome	Tolterodine	Imipramine	Relative risk (95% CI)	Absolute effect	Quality
Number of children with slight mood change	1/27 (3.7%)	3/27 (11.1%)	RR 0.33 (0.04 to 3.01)	74 fewer per 1000 (from 107 fewer to 223 more)	LOW

17.2.2. Health economic evidence review

Given the lack of published evidence assessing the cost-effectiveness of different interventions used in the initial and subsequent treatment of bedwetting, the GDG identified this area as high priority for original economic analysis. Therefore, a cost-utility analysis was undertaken where costs and quality-adjusted life-years (QALYs) were considered from a UK National Health Service and Personal Social Services perspective. The time horizon for the analysis was 13 years, modelling patients from the time they entered at age 7 years until they reached age 20.

A summary of the analysis is provided below. The full report is presented in appendix G.

Summary of results

The results of the probabilistic sensitivity analysis are summarised in table 17-16 in terms of mean total costs and mean total QALYs and mean net benefit for each treatment sequence, where each mean is the average of 20,000 simulated estimates. The option with the greatest mean net benefit is the most cost-effective at a specified threshold (for example, £20,000). The percentage of simulations where each strategy was the most cost-effective gives an indication of the strength of evidence in favour of that strategy being cost-effective.

Table 17-16

Basecase probabilistic sensitivity analysis results.

The results of the incremental analysis in the probabilistic analysis, excluding dominated and extendedly dominated strategies, are presented in table 17-17.

Table 17-17

Incremental analysis of basecase probabilistic results with dominated and extendedly dominated sequences removed.

The differences between intervention sequences were relatively small and the probabilistic results indicated substantial uncertainty around the mean cost and benefit estimates. Small changes to the model inputs appear to result in substantial changes to the conclusions about modelled sequences' relative and overall cost-effectiveness.

Results of the basecase probabilistic analysis indicate that a cost-effective second line treatment for children who have not responded to alarm alone is combined alarm and desmopressin. For children who have not responded to desmopressin alone, a cost-effective second line option is a switch to alarm alone. However, in a group of children for whom alarms are not appropriate, it is cost-effective to try the addition of an anticholinergic to desmopressin. Even as a second line intervention, imipramine was never found to be cost-effective.

The economic analysis conducted and presented here represents the first undertaken to assess the cost-effectiveness of interventions used in the treatment of children with bedwetting. Although the analysis is directly applicable to decision making in the UK NHS, it has some potentially serious limitations, some of which may significantly impact the overall conclusions that can be drawn. The main limitations of the analysis are related to the fact that assumptions had to be made in the absence of evidence. Some of these key assumptions centre around:

• health care resource use having been estimated by GDG

• utility weights having been estimated by GDG

A full discussion of these can be found in appendix G.

17.2.3. Evidence statements

Studies including children with bedwetting and possible daytime symptoms

Children who have not responded to ENURESIS ALARM therapy

Enuresis alarm compared to modified dry bed training with an enuresis alarm

Butler (1988) ¹⁵¹, Butler (1990) ¹¹²

• Two studies showed children treated with an enuresis alarm were more likely to achieve 14 consecutive dry nights compared to children treated with modified dry bed training and an enuresis alarm. Relative risk 1.52, 95% CI 1.14, 2.04. Children in Butler (1988) had a mean age of 9.7 years and had 16 weeks of treatment, 48.6% were resistant to enuresis alarm treatment. In Butler (1990) the mean age was 10.6 years and treatment was for 16 weeks, all children were resistant to enuresis alarms.

• One study showed children treated with modified dry bed training with an enuresis alarm had 0.76 fewer wet nights per week at the end of treatment compared to children treated with an enuresis alarm. No information on variability was given in the study. Therefore calculation of standard deviation was not possible and the mean difference and CI were not estimable.

• One study showed children treated with an enuresis alarm had 0.2 fewer wet nights per week at the end of treatment compared to children treated with modified dry bed training with an enuresis alarm. No information on variability was given in the study. Therefore calculation of standard deviation was not possible and the mean difference and CI were not estimable.

• Children in Butler (1988) had a mean age of 9.7 years and had 16 weeks of treatment, 48.6% were resistant to enuresis alarm treatment. In Butler (1990) the mean age was 10.6 years and treatment was for 16 weeks, all children were resistant to enuresis alarms.

• Two studies showed there was no statistically significant difference in the number of children who relapsed between children treated with an enuresis alarm and children treated with modified dry bed training with an enuresis alarm. Relative risk 1.14, 95% CI 0.63, 2.07. Children in Butler (1988) had a mean age of 9.7 years and had 16 weeks of treatment, 48.6% were resistant to enuresis alarm treatment. In Butler (1990) the mean age was 10.6 years and treatment was for 16 weeks, all children were resistant to enuresis alarms.

Butler (1990) ¹¹²

• One study showed there was no statistically significant difference in the number of children who dropped out between children treated with an enuresis alarm and children treated with modified dry bed training and an enuresis alarm. Relative risk 0.5, 95% CI 0.05, 5.15. Children had a mean age of 10.6 years and treatment was for 16 weeks. All children were resistant to enuresis alarms.

Desmopressin compared to placebo

Dimson (1986) ¹⁵²

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 20 micrograms intranasal desmopressin and children treated with a placebo. Relative risk 5, 95% CI 0.26, 97. Children had an age range of 6 to 13 years and had 2 weeks of treatment. All were resistant to enuresis alarm treatment.

• One study showed children treated with 20 micrograms intranasal desmopressin had 1.6 fewer wet nights per week at the end of treatment than children treated with placebo. Children had an age range of 6 to 13 years and had 2 weeks of treatment, all were resistant to enuresis alarm treatment. The studies did not give standard deviation values and therefore the mean difference and CI were not estimable.

• One study showed all children treated with 20 micrograms intranasal desmopressin (2 out of 2) relapsed. No children in the placebo group became dry and therefore could not relapse. Children had an age range of 6 to 13 years and had 2 weeks of treatment. All were resistant to enuresis alarm treatment.

Children who have not responded to desmopressin

Enuresis alarm and placebo compared to enuresis alarm and desmopressin

Gibb (2004) ¹⁵³

• One study showed there was no statistically significant difference in the number of children who achieved 28 consecutive dry nights between children treated with an enuresis alarm and placebo and children treated with an enuresis alarm and 20 – 40 micrograms intranasal desmopressin. Relative risk 0.93, 95% CI 0.71, 1.23. Children had a mean age of 8.3 and 8.5 years and had 2 months of treatment, all children were resistant to desmopressin.

• One study showed children treated with an enuresis alarm and 20 – 40 micrograms intranasal desmopressin had fewer wet nights per week at the end of treatment compared to children treated with enuresis alarm and placebo. Mean difference 0.6, 95% CI 0.23, 0.97. Children had a mean age of 8.3 and 8.5 years and had 2 months of treatment, all children were resistant to desmopressin.

• One study showed there was no statistically significant difference in the number of children who dropped out between children treated with an enuresis alarm and placebo and children treated with an enuresis alarm and 20 – 40 μg intranasal desmopressin. Relative Risk 1.8, 95% CI 0.84, 3.85. Children had a mean age of 8.3 and 8.5 years and had 2 months of treatment, all children were resistant to desmopressin.

Children who have not responded to desmopressin/ imipramine / oxybutynin

Acupuncture

Serel (2001) ¹⁵⁴

• One study showed children who had previously not responded to treatment with desmopressin, imipramine or oxybutynin could respond to treatment with acupuncture. The study showed 86% of children treated with acupuncture were completely dry within 6 months of starting treatment. Children had a mean age of 10.3 years and had 6 months of treatment. All children had failed to respond to desmopressin, imipramine or oxybutynin.

Studies including children with severe bedwetting and possible daytime symptoms

Children who have not responded to enuresis alarm therapy

Desmopressin compared to placebo for children with severe wetting (excludes studies which only included children with bedwetting) for children who have not responded to enuresis alarm therapy

Terho (1991) ¹⁵⁵

• One study showed children treated with 20 to 40 μg intranasal desmopressin had 2.3 fewer wet nights per week at the end of treatment than children treated with placebo. Children had an age range of 5 to 13 years and had 3 weeks of treatment, 48% were resistant to enuresis alarms. The studies did not give standard deviation values and therefore the mean difference and CI were not estimable.

Studies including children with bedwetting only

Children who have not responded to enuresis alarm therapy or demopressin

Desmopressin compared to a placebo

Fjellestad (1987) ¹⁵⁶

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 200 micrograms tablet desmopressin and children treated with placebo. Relative risk 5, 95% CI 0.25, 99.95. Children had a mean age of 9.8 years and had 2 weeks of treatment. 60% were resistant to enuresis alarms and 23% were resistant to desmopressin.

• One study showed children treated with 200 micrograms tablet desmopressin had 1.5 fewer wet nights per week at the end of treatment compared to children treated with placebo. Children had a mean age of 9.8 years and had 2 weeks of treatment. 60% were resistant to enuresis alarms and 23% were resistant to desmopressin. No information on variability was given in the study, therefore calculation of standard deviation was not possible and the mean difference and CI were not estimable.

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 20 micrograms intranasal desmopressin and children treated with placebo. Relative risk 3, 95% CI 0.13, 70.83. Children had a mean age of 9.8 years and had 2 weeks of treatment. 60% were resistant to enuresis alarms and 23% were resistant to desmopressin.

• One study showed children treated with 20 micrograms intranasal desmopressin had 1.6 fewer wet nights per week at the end of treatment compared to children treated with placebo. Children had a mean age of 9.8 years and had 2 weeks of treatment. 60% were resistant to enuresis alarms and 23% were resistant to desmopressin. No information on variability was given in the study, therefore calculation of standard deviation was not possible and the mean difference and CI were not estimable.

Stenberg (1994) ¹⁵⁷

• One study showed children treated with 200 to 400 micrograms tablet desmopressin had fewer wet nights per week at the end of treatment compared to children treated with placebo. Mean difference −2.3, 95% CI −3.37, −1.03. Children had a mean age of 13.5 years and had 2 weeks of treatment. All were resistant to desmopressin or enuresis alarms.

Tablet desmopressin compared to intranasal desmopressin

Fjellestad (1987) ¹⁵⁶

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 20 mcg intranasal desmopressin and children treated with 200 μg tablet desmopressin. Relative risk 2, 95% CI 0.19, 20.9. Children had a mean age of 9.8 years and had 2 weeks of treatment. 60% were resistant to enuresis alarms and 23% were resistant to desmopressin.

• One study showed children treated with 20 micrograms intranasal desmopressin had 0.1 fewer wet nights per week at the end of treatment compared to children treated with 200 μg tablet desmopressin. Children had a mean age of 9.8 years and had 2 weeks of treatment. 60% were resistant to enuresis alarms and 23% were resistant to desmopressin. No information on variability was given in the study, therefore calculation of standard deviation was not possible and the mean difference and CI were not estimable.

Children who have not responded to enuresis alarm therapy and desmopressin

Imipramine compared to placebo

Neveus (2008) ¹⁵⁸

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 25 to 50 mg imipramine and children treated with placebo. Relative risk 11, 95% CI 0.64, 188.95. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no statistically significant difference in the number of children who achieved greater than 50% improvement in the number of dry nights between children treated with 25 to 50 mg imipramine and children treated with placebo. Relative risk 5, 95% CI 0.25, 99.16. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed children treated with 25 to 50 mg imipramine had fewer wet nights in the last 2 weeks of treatment compared to children treated with placebo. Mean difference −3.2, 95% CI −5.72, −0.68. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no difference in the number of children who dropped out between children treated with 25 to 50 mg imipramine and children treated with placebo. Relative risk 1, 95% CI 0.07, 15.12. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

Imipramine compared to tolterodine

Neveus (2008) ¹⁵⁸

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 25 to 50 mg imipramine and children treated with 1 to 2 mg tolterodine. Relative risk 11, 95% CI 0.64, 188.95. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no statistically significant difference in the number of children who achieved greater than 50% improvement in the number of dry nights between children treated with 25 to 50 mg imipramine and children treated with 1 to 2 mg tolterodine. Relative risk 2, 95% CI 0.19, 20.67. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed children treated with 25 to 50 mg imipramine had fewer wet nights in the last 2 weeks of treatment compared to children treated with 1 to 2 mg tolterodine. Mean difference −2.6, 95% CI −5.12, −0.08. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no statistically significant difference in the number of children who dropped out between children treated with 25 to 50 mg imipramine and children treated with 1 to 2 mg tolterodine. Relative risk 3, 95% CI 0.13, 70.3. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

Tolterodine compared to placebo

Neveus (2008) ¹⁵⁸

• One study showed there was no difference in the number of children who achieved 14 consecutive dry nights between children treated with 1 to 2 mg tolterodine and children treated with placebo. No children in either treatment group achieved 14 consecutive dry nights. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no statistically significant difference in the number of children who achieved greater than 50% improvement in the number of dry nights between children treated with 1 to 2 mg tolterodine and children treated with placebo. Relative risk 3, 95% CI 0.13, 70.3. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no statistically significant difference in the number of wet nights in the last 2 weeks of treatment between children treated with 1 to 2 mg tolterodine and children treated with placebo. Mean difference −0.6, 95% CI −2.76, 1.56. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

• One study showed there was no statistically significant difference in the number of children who dropped out between children treated with 1 to 2 mg tolterodine and children treated with placebo. Relative risk 0.33, 95% CI 0.01, 7.81. Children had a mean age of 9.4 years and had 5 weeks of treatment. All children were resistant to 6 months of enuresis alarms and desmopressin.

Studies include children with severe bedwetting only

Children who have not responded to desmopressin

Desmopressin for children who had previously failed treatment with desmopressin (children with severe bedwetting)

Wikstrom (1997) ¹⁵⁹

• One observational trial showed children who had failed to respond to desmopressin could respond to repeated 20 to 40 μg intranasal desmopressin treatment (50% response rate). Children had an age range of 7 to 18 years and had 6 to 9 months of treatment.

• One observational trial showed children who had failed to respond to repeated treatments with desmopressin could respond to treatment with an enuresis alarm and 20 to 40 μg intranasal desmopressin (53% response rate). Children had an age range of 7 to 18 years and had 6 to 9 months of treatment.

Studies including children with monosymptomatic nocturnal enuresis

Children who have not responded to Alarms

Alarm combined with desmopressin

Vogt (2009) ¹⁶⁰

• One study showed children who had failed to respond to alarms could respond to combined desmopressin and alarm therapy. 11 out of 14 children became dry (maximum of 2 wet nights per month). Children had a mean age of 10.05 years and had 3 months of treatment.

• One study showed children who had failed to respond to alarms could respond to combined desmopressin and alarm therapy, 0 out of 11 children relapsed after 1 year of becoming dry Children had a mean age of 10.05 years and had 3 months of treatment.

Children who have not responded to DESMOPRESSIN

Desmopressin and placebo compared to desmopressin and tolterodine

Austin (2008) ¹⁶¹

• One study showed there was no statistically significant difference in the number of children who achieved 14 consecutive dry nights between children treated with 600 micrograms desmopressin and placebo and children treated with 600 micrograms desmopressin and 4 mg tolterodine. Relative risk 0.38, 95% CI 0.04, 3.25. Children had a mean age of 10.5 years and had 1 month of treatment. All children were non- or partial responders to desmopressin.

• One study showed there was no statistically significant difference in the number of children who achieved greater than 50% improvement in the number of dry nights between children treated with 0.6 mg desmopressin and placebo and children treated with 600 micrograms desmopressin and 4 mg tolterodine. Relative risk 0.9, 95% CI 0.29, 2.78. Children had a mean age of 10.5 years and had 1 month of treatment. All children were non- or partial responders to desmopressin.

Enuresis alarm

Tuygun (2007)¹¹⁶

• One study showed children who had failed to respond to desmopressin could respond to second line enuresis alarm therapy; 68.42% achieved a >90% decrease in number of wet nights. Children had a median age of 8 years and had 3 months of treatment.

• One study showed children who had failed to respond to desmopressin could respond to second line enuresis alarm therapy; 15.78% achieved 50 to 90% reduction in the number of wet nights. Children had a median age of 8 years and had 3 months of treatment.

• One study showed children who had failed to respond to desmopressin had a mean number of wet nights per month at the end of treatment was 5.5 (SD 10.65). Children had a median age of 8 years and had 3 months of treatment.

• One study showed children who had failed to respond to desmopressin had a relapse rate of 31.57% at 6 months. Children had a median age of 8 years and had 3 months of treatment.

Desmopressin combined with alarms

Vogt (2009)¹⁶⁰

• One study showed children who had failed to respond to desmopressin could respond to combined desmopressin and alarm therapy. 11 out of 16 children became dry (maximum of 2 wet nights per month). Children had a mean age of 9.81 years and had 3 months of treatment.

• One study showed children who had failed to respond to desmopressin could respond to combined desmopressin and alarm therapy. However 1 out of 11 children relapsed after 1 year of becoming dry Children had a mean age of 9.81 years and had 3 months of treatment.

Desmopressin combined with oxybutynin

Radvanska (2006)¹⁶²

• One observational study showed children treated with desmopressin and oxybutynin significantly reduces the mean number of wet nights per week in children with monosymptomatic nocturnal enuresis who are non responders to desmopressin. Children had a mean age of 10.1 (SD 2.1) years and had 2 weeks of treatment.

Side effects of second line treatments

Desmopressin and enuresis alarm compared to enuresis alarm and placebo for children treatment resistant to desmopressin

Gibb (2004)¹⁵³

One study showed no statistically significant difference in the number of children having headaches between children treated with enuresis alarms and desmopressin and children treated with enuresis alarm and placebo. Relative risk 3.15, 95% CI 0.13, 76.37. Children had a mean age of 8.3 to 8.5 years and had 2 months of treatment.

Desmopressin compared to placebo for children treatment resistant to enuresis alarms with severe bedwetting

Stenberg (1994)¹⁵⁷

• One study showed no statistically significant difference in the number of children having headaches between children treated with desmopressin and children treated with placebo. Relative risk 11, 95% CI 0.69, 175.86. Children had a mean age of 13.5 years and had 2 weeks of treatment.

• One study showed no statistically significant difference in the number of children having abdominal pain between children treated with desmopressin and children treated with placebo. Relative risk 13, 95% CI 0.83, 203.83. Children had a mean age of 13.5 years and had 2 weeks of treatment.

• One study showed no statistically significant difference in the number of children having nausea and vertigo between children treated with desmopressin and children treated with placebo. Relative risk 3, 95% CI 0.14, 65.9. Children had a mean age of 13.5 years and had 2 weeks of treatment.

Imipramine compared to tolterodine for children treatment resistant to enuresis alarms and desmopressin

Neveus (2008)¹⁵⁸

• One randomised controlled trial showed there was no statistically significant difference in the number of children with slight mood change between children treated with imipramine and children treated with tolterodine. Relative risk 3, 95% CI 0.33, 27.06. Children had a mean age of 9.4 years and had 6 weeks of treatment.

• One randomised controlled trial showed there was no statistically significant difference in the number of children with insomnia between children treated with imipramine and children treated with tolterodine. Relative risk 5, 95% CI 0.25, 99.51. Children had a mean age of 9.4 years and had 6 weeks of treatment.

• One randomised controlled trial showed there was no statistically significant difference in the number of children with palpitations between children treated with imipramine and children treated with tolterodine. Relative risk 3, 95% CI 0.13, 70.53. Children had a mean age of 9.4 years and had 6 weeks of treatment.

• One randomised controlled trial showed there was no statistically significant difference in the number of children with slight nausea between children treated with imipramine and children treated with tolterodine. Relative risk 5, 95% CI 0.25, 99.51. Children had a mean age of 9.4 years and had 6 weeks of treatment.

Tolterodine compared to imipramine for children treatment resistant to enuresis alarms and desmopressin

Neveus (2008)¹⁵⁸

• One randomised controlled trial showed there was no statistically significant difference in the number of children with slight mood change between children treated with tolterodine and children treated with imipramine. Relative risk 0.33, 95% CI 0.04, 3.01. Children had a mean age of 9.4 years and had 6 weeks of treatment.

17.2.4. Health economic evidence statements

NCGC economic evaluation (see appendix G)

• Switching to treatment with combined alarm and desmopressin following a non- or partial response to initial treatment with alarm alone is cost-effective in the treatment of children with bedwetting. This evidence has potentially serious limitations and direct applicability.

• Switching to desmopressin treatment following a non- or partial response to second line treatment with combined alarm and desmopressin is cost-effective in the treatment of children with bedwetting. This evidence has potentially serious limitations and direct applicability.

• The addition of an anticholinergic to desmopressin when desmopressin alone has only produced a partial response is likely to be cost-effective in the treatment of children with bedwetting. This evidence has potentially serious limitations and direct applicability.

• Switching to alarm treatment following a non- or partial response to initial treatment with despmoressin may be a cost-effective step in the treatment of children with bedwetting. This evidence has potentially serious limitations and direct applicability.

• Switching to treatment with combined alarm and desmopressin following a non- or partial response to initial treatment with desmopressin alone is not cost-effective in the treatment of children with bedwetting. This evidence has potentially serious limitations and direct applicability.

• Use of repeated courses of desmopressin in children who experience a recurrence of bedwetting whenever it is withdrawn is cost-effective as a long term management of bedwetting. This evidence has potentially serious limitations and direct applicability.

• Use of repeated courses of combined desmopressin and anticholinergic in children who experience a recurrence of bedwetting whenever treatment is withdrawn is likely to be cost-effective as a long term management of bedwetting. This evidence has potentially serious limitations and direct applicability.

17.2.5. Evidence to recommendations

Relative values of different outcomes

In the evidence review of direct combination the outcomes indicating success of treatment and follow up were examined. The GDG considered that mean reduction in wet nights might be a useful outcome from clinical perspective. The GDG considered that although sustained dryness is what both children nd young people and parents or carers wish for when engaging in treatment, when children and young people do not respond to initial treatments, reduction in wet nights may indicate a useful improvement in symptoms even if dryness is not achieved.

Trade off between clinical benefit and harms

The harms related to individual pharmacological choices are outlined in the relevant chapters.

Economic considerations

Original modelling undertaken for this guideline showed that the combination of alarm and desmopressin was a likely cost-effective option following a non- or partial response to alarm alone. The addition of desmopressin represents an increase in cost, but one that is reasonable given the associated health gain. The analysis also indicates that if these patients do not achieve a full or sustained response, offering desmopressin alone is a cost-effective next step.

Original modelling undertaken for this guideline showed that when treatment with desmopressin does not produce a response, offering alarm alone may be a cost-effective next step. Clinical evidence indicated that combined alarm and desmopressin treatment following a non-response to desmopressin alone is unlikely to be any more effective than switching to alarm alone. Because combined treatment is more expensive than alarm treatment on its own and no more effective, it would not represent a good use of NHS resources.

Original modelling undertaken for this guideline showed that offering combined anticholinergic with desmopressin where desmopressin alone produced only a partial response, is likely to provide additional health gain and for a reasonable cost to the NHS.

The analysis from which these conclusions are derived showed that there was considerable uncertainty about which sequence of interventions was the most cost-effective, and this was likely caused by the uncertainty around estimates of treatment effectiveness observed in the pair-wise and network meta-analyses.

Quality of evidence (this includes clinical and economic)

The quality of evidence for outcomes in direct combinations was low or very low.

Other considerations

The GDG used evidence from direct comparisons and health economic analyses to develop the recommendations. The findings of the health economic analysis were important in considering the sequencing of treatments to use following non-response or partial response to initial treatment.

The experience of the GDG was that although alarm and desmopressin in combination following alarm treatment were shown to be clinically and cost effective, some children, young people and parents or carers will not be willing to continue alarm unless they have experienced some benefit from it and may prefer desmopressin alone as the next management option.

The GDG considered that where possible alarm is the first line treatment of choice. When children and young people do not respond to desmopressin considering again whether alarm is a suitable treatment might be appropriate. The child and young person may be older than when they had tried desmopressin or alarm may not have been suitable because of the child or young person's age or maturity or for family reasons.

Response rate for alarm in second line treatment is comparable to first line treatment for both full response (90% reduction in the number of wet nights), and partial response (50% reduction in the number of wet nights) and the mean number of wet nights when children and young people were treated with enuresis alarms following lack of response to desmopressin.

For children and young people who are resistant to desmopressin there is no advantage in continuing desmopressin with an enuresis alarm.

The GDG discussed how the combination of alarm and desmopressin should be used. In the studies of this combination, desmopressin was added in exactly the same way as when using desmopressin on its own, i.e. start with lower dose and then increased dose 1–2 weeks later if no response.

Evidence for the association between certain clinical and/or social or emotional factors and likelihood of response was reviewed as part of the initial assessment chapter, and was regarded as very poor quality. Therefore, the recommendation to refer patients who have not responded to repeated courses of treatment for further assessment was informed by the professional opinion of the GDG, based on their clinical knowledge, understanding of pathophysiology of bedwetting and the patient and carer member's personal experiences.

The direct evidence review failed to find benefit for the addition of tolterodine to desmopressin for children and young people who had not responded to desmopressin. The GDG considered the study inadequately powered to show difference and indicated that this combination may be useful in their clinical experience. The health economic analysis supported the clinical consensus of the GDG indicating possible gain at acceptable cost. The GDG however also considered the evidence that the effect of desmopressin and of desmopressin and anti-cholinergic may continue to improve up to 6 months (see Evidence review – Lee (2005) ²⁵). They considered it acceptable to continue treatment for 6 months on desmopressin alone before adding an anti-cholinergic but that the choice between these strategies would need to be individualized to the child, young person and parent or carer.

17.2.6. Recommendations

17.2.6.1.

If bedwetting does not respond to initial alarm treatment, offer:

• combination treatment with an alarm and desmopressin or

• desmopressin alone if continued use of alarm is no longer acceptable to the child or young person or their parents and carers. [1.9.1]

17.2.6.2.

Offer desmopressin alone to children and young people with bedwetting if there has been a partial response to a combination of an alarm and desmopressin following initial treatment with an alarm.[1.9.2]

17.2.6.3.

Consider advising that desmopressin should be taken 1–2 hours before bedtime in children and young people with bedwetting that has either partially responded or not responded to desmopressin taken at bedtime. Ensure that the child or young person can comply with fluid restriction starting from 1 hour before drug is taken.[1.10.10]

17.2.6.4.

Consider continuing treatment with desmopressin for children and young people with bedwetting that has partially responded, as bedwetting may improve for up to 6 months after starting treatment.[1.10.11]

17.2.6.5.

Consider using repeated courses of desmopressin combined with an anticholinergic in children and young people who have responded to this combination but experience repeated recurrences of bedwetting following previous response to treatment.[1.13.5]

17.2.6.6.

Refer children and young people with bedwetting that has not responded to courses of treatment with an alarm and/or desmopressin for further review and assessment of factors that may be associated with a poor response, such as an overactive bladder, an underlying disease or social and emotional factors.[1.12.1]

17.2.6.7.

Consider an anticholinergic combined with desmopressin for children and young people who have been assessed by a healthcare professional with expertise in the management of bedwetting that has not responded to an alarm and/or desmopressin and have any of the following:

• bedwetting that has partially responded to desmopressin alone

• bedwetting that has not responded to desmopressin alone

• bedwetting that has not responded to combination of alarm and desmopressin. [1.13.3]

17.2.6.8.

Consider continuing treatment for children and young people with bedwetting that has partially responded to desmopressin combined with an anticholinergic as bedwetting may continue to improve for up to 6 months after starting treatment.[1.13.4]

What to Do if Desmopressin Doesn T Work

Source: https://www.ncbi.nlm.nih.gov/books/NBK62714/

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