Enuresis is one of the most common functional developmental disorders affecting children. Current treatment strategies of primary nocturnal enuresis are facing two major weaknesses:  moderate success rate and very high relapse rate.
Desmopressin, a synthetic analog of arginine vasopressin (ADH), released by the posterior pituitary gland reduces urine production by increasing water reabsorption by the collecting tubules, is currently considered the first line therapy for monosymptomatic enuresis.[1] Relapse rate after discontinuation of desmopressin is as high as 70%[2]

The objective was to  introduce a new protocol to patients with primary nocturnal enuresis to increase efficacy of treatment and decrease relapse rate.

A prospective study was done on 185 children diagnosed with nocturnal enuresis between the year 2007 and 2014. Patients were either referred by pediatricians or presented directly to our clinic. Inclusion criteria consisted of: age> 5 years, monosymptomatic enuresis or non-monosymptomatic enuresis, strict abidance by the protocol; follow up lasting at least 24 months. Of these 185 children, 122 were included in the study and 63 were eliminated. The mean follow up time was 62 months and 24 months at least. 
All participants were started on a combination therapy of desmopressin 120 microgram (MELT formula) once per day and propiverine 7.5 milligram twice per day, which were then escalated or structurally withdrawn as per their response to therapy and our designed protocol.

Outcome was defined as per the International Children Continence Society (ICCS) latest definitions of complete success, relapse and failure of therapy. Initial success indicates reduction of episodes in less than 50%. Partial response denotes a reduction of symptoms from 50 to 99%. Complete response designates 100% reduction.
Concerning the Long-term success, it is divided into 3 phases. Relapse phase: more than one symptom recurrence per month. Continued success phase: no relapse in 6 months after interruption of treatment. Complete success phase: no relapse in two years after interruption of treatment. [3]

Statistical analysis was performed by SPSS, version 22. Chi-Square, Anova and t-test, were used to identify the correlation between variables. Statistical significance was represented by a p value of <0.05.

Our results have shown that 100% of the patients who did not abide by our protocol and stopped their treatment abruptly after a dry period, relapsed compared to a 13% relapse rate for those who abided by the protocol. 66% needed only the minimum time required by our protocol and demonstrated complete success whereas 21% needed higher dosage or more time to reach the full success phase. Our overall complete success after follow up on all the patients included was as high as 87% with only 13% failures and relapse over the whole period of our study. 

Age, gender and type of primary nocturnal enuresis had no effect over success (p>0.05).

Using a combination therapy of desmopressin and anticholinergic in a structured withdrawal protocol being both time and dose dependent has shown high success rates along with a relatively low relapse rate of 13%, irrespective of the enuresis type, gender or age of the patient. Parents of enuretic children are solely bothered by the enuresis and its impact on the social and psychological status of the child, and hence neglect or fail to report the daytime symptoms. Enuresis has a complex pathophysiology with multiple systems involved which led us to use a combination therapy on monosymptomatic and non-monosymptomatic enuresis. Gradually withdrawing the medications once clinical response was demonstrated increased the lasting effect of therapy.
Age, gender and type of primary nocturnal enuresis had no effect over the outcome which adds to the complexity of enuresis and renders our protocol more convenient to different patients.

A structured withdrawal program may impose a prolongation of treatment in children who already had a response to therapy, and this may affect the compliance of the patient and parents to treatment.With the high relapse rates that abrupt desmopressin stoppage is demonstrating, it is crucial though to insist on a plan and to rely on a protocol to gradually withdraw the medications for the patient to continue demonstrating the effect of therapy. Our protocol showed promising results, but the greater number and the presence of a placebo group would increase the strength of our results.

Vande Walle J, Rittig S, Bauer S, Eggert P, Marschall-Kehrel D, Tekgul S. Practical consensus guidelines for the management of enuresis. Eur J Pediatr. 2012;171(6):971-983. doi:10.1007/s00431-012-1687-7.
Wille S. Comparison of desmopressin and enuresis alarm for nocturnal enuresis. Arch Dis Child. 1986;61(1):30-33. doi:10.1136/adc.61.1.30.
Austin P, Bauer S, Bower W, et al. The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children's Continence Society. Neurourol Urodyn. 2015;35(4):471-481. doi:10.1002/nau.22751.http://dx.doi.org/10.1002/nau.22751