[Results of a therapeutic strategy against monosymptomatic nocturnal enuresis]. Efficacy of desmopressin combined with alarm therapy for monosymptomatic nocturnal enuresis. Combined therapy of enuresis alarm and desmopressin in the treatment of nocturnal enuresis. Evidence against a synergistic effect of desmopressin with conditioning in the treatment of nocturnal enuresis. Comparing alarms, desmopressin, and combined treatment in Chinese enuretic children. Comparison of desmopressin and enuresis alarm for nocturnal enuresis. [Treatment of isolated nocturnal enuresis: alarm or desmopressin?]. Tolterodine and imipramine in refractory enuresis; a placebo-controlled crossover study. Comparison of effects of treatment of primary nocturnal enuresis with oxybutynin plus desmopressin, desmopressin alone or imipramine alone: a randomized controlled clinical trial. Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis. Desmopressin in nocturnal enuresis.
There are many therapeutic options against enuresis.
                To evaluate several therapies introduced progressively to treat monosymptomatic nocturnal enuresis.
                Eighty-four patients, aged 6 to 14 years old, were studied. The 67 year olds were treated with desmopressin and oxybutynin was added in nonresponders. If enuresis persisted, Alarm was given. Children over 7 years of age were randomly divided and treated with Alarm or Alarm plus desmopressin. Nonresponders were treated with desmopressin alone.
                In children aged 6-7 years the cumulative response was 72%. Those who wetted themselves less responded to desmopressin. In children over 7 years of age, response to Alarm was 73.3% and response to Alarm plus desmopressin was 58.6%. In nonresponders the cumulative response after desmopressin treatment increased to 80% and 62% respectively.
                In the group of 6 to 7 year-olds desmopressin was indicated as first line therapy. Treatment efficacy was increased by adding oxybutynin especially in the children who wetted themselves the most. In children over 7 years of age Alarm was the most effective treatment and relapses were fewer. No advantages were observed with the combination of Alarm and desmopressin in our protocol. We evaluated the combination of alarm and desmopressin versus alarm monotherapy for the treatment of nocturnal enuresis.
                A double-blind, placebo controlled study of alarm therapy combined with desmopressin for children with nocturnal enuresis is described. Of 93 patients 47 were randomized to receive alarm therapy and 40 microg. intranasal desmopressin for 3 weeks followed by 20 microg. desmopressin for 3 weeks (group 1) and 46 received alarm therapy and placebo (group 2). After 6 weeks on alarm therapy and medication or placebo, both groups received an additional 3 weeks of alarm monotherapy. A specialized nurse practitioner advised patients and families of the treatment to be given at home and in the outpatient department. Bed-wetting frequency was evaluated before during and 2 weeks and 6 months after treatment.
                A significantly greater reduction in the number of wet nights was observed after the first 3 weeks of treatment in group 1. However, after long-term followup no significant differences in bed-wetting frequency were noted.
                There is a temporary, positive effect on enuresis using desmopressin combined with alarm therapy. However, both treatment modalities have a low long-term success rate of 36% to 37%. Twenty-eight children with primary nocturnal enuresis were blindly allocated at random to a combination of enuresis alarm and 20 micrograms intranasal desmopressin or alarm and placebo for 2 weeks. Patients received the other therapy after a 2-week treatment-free period. The combined treatment of desmopressin and alarm showed 5.1 +/- 0.4 (mean +/- SEM) dry nights per week and resulted in significantly more dry nights per week during the 2 weeks of observation than placebo and alarm (4.1 +/- 0.4, P less than 0.05). To test the hypothesis that desmopressin facilitates acquisition of continence, we aimed to establish whether, in children with nocturnal enuresis who are desmopressin nonresponders, adjunct desmopressin increases the rate of sustained continence after treatment with a conditioning alarm. Study design Patients with nocturnal enuresis (n=358; age range, 6-16 years) completed a 4-week "run-in" course of intranasal desmopressin (20-40 microg). Of these, 207 defined as nonresponders (<50% reduction in wet nights) were randomly assigned to receive either desmopressin (n=101) or placebo (n=106) nasal spray, together with conditioning alarm therapy for 8 weeks. Principal outcome measures were remission (28 continuous dry nights) and relapse (>2 wet nights in 2 weeks after having achieved remission).
                Remission rates were similar in both groups (51.5% desmopressin, 48.1% placebo; 95% CI on difference, -10%, 17%; P=.63), and relapse rates were not significantly different (13.5% vs 5.9%; 95% CI on difference, -3.7%, 19%; P=.19). Although remission rates were similar, children treated with desmopressin had significantly more dry nights during treatment than those in the placebo group.
                Desmopressin did not act synergistically with alarm treatment to achieve remission. Therefore, we infer that in partial or nonresponders, desmopressin does not enhance learning. The objective of this multicenter randomized controlled trial was to compare the efficacy of enuresis alarms, oral desmopressin, and combined treatment in Chinese children with monosymptomatic primary nocturnal enuresis. We assigned 105 children aged 7-15 years to receive alarms (group 1, 35 patients), oral desmopressin 400 mug (group 2, 38 patients), or combined therapy (group 3, 32 patients) for 12 weeks; patients were then followed for 12 weeks after treatment. The wetting frequency decreased during treatment by 46%, 52%, and 73% in groups 1, 2, and 3, respectively. In groups 2 and 3, but not in group 1, there was rebound post treatment, but significant improvements persisted at 12 weeks. The complete and partial response rates were 22.9% and 20%, respectively in group 1, 42% and 10.5% in group 2, and 62.5% and 15.6% in group 3. By Kaplan-Meier analysis, group 1 had a significantly poorer response than groups 2 and 3. Of the responders, 20%, 60%, and 40% in groups 1, 2, and 3, respectively, relapsed after stopping treatment. In conclusion, enuresis alarms and/or oral desmopressin were less efficacious in Chinese than in Western societies. Desmopressin produced an immediate effect but relapses were common. Alarms took several weeks to produce a benefit, which was persistent on follow-up. Fifty children with primary nocturnal enuresis were randomised for a study comparing desmopressin (DDAVP) and enuresis alarm. Forty six completed the trial, 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months. Failures were crossed over and relapses were continued on the same treatment for a further three months. The improvement rate was 70% in the group given desmopressin and 86% in the group treated with alarm; the difference was not significant. During the first week of treatment the group given desmopressin was significantly dryer, and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm. No serious side effects were observed. This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis. When this fails or when a safe drug with rapid effect is needed, however, desmopressin is a useful alternative. Monosymptomatic nocturnal enuresis is common in healthy school children. Treatment is often required because of social and psychological convenience. We therefore conducted a randomized prospective trial using either desmopressin (D) or alarm (A).
                Patients (n = 135) aged 6 to 16 years were enrolled between January 1992 and December 1994. Desmopressin (Minirin spray, Ferring SA) was given intranasally at a dose of 20 micrograms at bedtime and increased to 40 micrograms after 2 weeks if partial result was obtained. The alarm was a pad-bell device (Wet-stop, Sega) and the sound source was attached to the upper part of the pajamas. Inclusion criteria were: primary monosymptomatic nocturnal enuresis in healthy children, age > or = 6 years, absence of previous treatment using either desmopressin or alarm. The aim of the treatment was to achieve 100% dry nights. Patients were evaluated after 15 days on therapy by phone call and thereafter by attending the outpatient clinic at 2-3 and 4-6 months. At the time of the second evaluation, a switch from alarm to desmopressin (or vice-versa) was proposed to those who did not respond to the initial treatment.
                In group D (n = 62), only 27 children were included since 12 (19%) were switched to alarm and 23 (37%) were excluded because they were either non-compliant or lost to follow-up. In group A (n = 73), only 31 were included since six (8%) were switched to desmopressin and 36 (49%) were excluded for the same reasons as in group D. Prior to inclusion, the percentage of dry nights was 21% in group D and 14% in group A. After 15 days on therapy, patients from group D achieved 80% dry nights compared to 50% in group A (P = 0.001). After 3 months, patients from group D attained 85% dry nights vs 90% in group A. After 6 months, children from group A achieved 94% dry nights vs 78% in group D (P = 0.01).
                Desmopressin offers better short-term results than enuresis alarm but the latter is significantly more efficient in the long term. In France, the alarm device is not reimbursed by the national health service and therefore is poorly accepted, as suggested from the high rate of patients lost to follow-up. The anticholinergic drug tolterodine has been suggested to be useful in therapy-resistant enuresis. Imipramine has a proven efficiency in unselected enuretic patients, but due to its side-effect profile it is only indicated, if at all, in therapy-resistant cases. We therefore compared these two drugs to placebo. Twenty-seven children with enuresis resistant to the alarm and to desmopressin in monotherapy were given placebo, tolterodine 1-2 mg, and imipramine 25-50 mg at bedtime for 5 weeks each in a randomised, double-blind, crossover fashion. The number of wet nights during the last 2 weeks of each treatment period was compared. One patient became spontaneously dry at the start of the study, and one dropped out due to side effects. Among the remaining 25 children, the number of wet nights during placebo, tolterodine and imipramine treatment were 11.0 +/- 3.9, 10.4 +/- 3.9 and 7.8 +/- 5.1, respectively (p < 0.001). Imipramine was significantly better than both placebo (p = 0.001) and tolterodine (p = 0.006). Nine children experienced side effects on imipramine and one on tolterodine (p = 0.001). This is the first study on anticholinergics or imipramine in children with therapy-resistant enuresis. Tolterodine, in monotherapy, had no proven effect. Imipramine was better than placebo, but side effects were common. We prospectively evaluated the efficacy of a combination of desmopressin and oxybutynin for treating children with nocturnal enuresis, compared to the single drugs imipramine and desmopressin.
                We enrolled 158 patients from 2003 to 2004. Children were randomly assigned to 1 of 3 groups and treated with desmopressin, imipramine or a combination of desmopressin plus oxybutynin. Of these patients 145 (100 boys and 45 girls, mean age 7.8 +/- 2.5 years, range 5 to 15) were followed for more than 6 months. Efficacy was measured at 1, 3 and 6 months in terms of average enuretic frequency, 5-scale response based on change in nocturnal enuretic frequency after treatment and posttreatment enuretic frequency as a percentage of pretreatment baseline frequency. The latter efficacy was classified according to daytime voiding symptoms. Statistical evaluation was performed using chi-square tests and ANOVA.
                Of the 145 children followed 48 received combination therapy, 49 received desmopressin and 48 received imipramine. A total of 68 patients (47%) had monosymptomatic enuresis and 77 (53%) had polysymptomatic enuresis. Combination therapy produced the best and most rapid results regardless of whether the children had monosymptomatic or polysymptomatic enuresis.
                Combination therapy with desmopressin plus oxybutynin for the treatment of pediatric nocturnal enuresis was well tolerated, and gave significantly faster and more cost-effective results than single drug therapy using either desmopressin or imipramine. Seventy-one children with nocturnal enuresis were enrolled in a controlled trial. The children were allocated to two matched groups. Children in both groups used an enuresis alarm until the end of treatment. Children in the first group were treated with 40 micrograms of intranasal desmopressin (Desmospray) for up to 6 weeks at the start of treatment with the alarm. During the observation period treatment there were 2.3 dry nights per week in both groups. At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups (6.3 in the alarm and desmopressin group and 4.8 in the alarm group) and also in the number of children becoming reliably dry. The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems. The effect of intranasal desmopressin on primary nocturnal enuresis was investigated in a study divided into 2 parts in which the first part was a randomized, double-blind, placebo-controlled cross-over study of 52 Finnish school children 5 to 13 years old. A variety of approaches had previously been attempted in most children, including water deprivation, night awakenings, enuresis alarm and imipramine, without success. The patients were randomized to 4 periods of 3 weeks each: 2 periods on placebo and 2 periods on 20 micrograms. desmopressin spray. The entire 12-week treatment period was preceded and followed by control periods (without treatment). The number of dry nights, measured as calculated averages per week, increased significantly (p less than 0.01) from 0.6 dry nights during pre-treatment to 4.3 and 4.6 dry nights per week during the 2 desmopressin treatment periods, respectively. The placebo responses were 2.1 and 2.4 dry nights per week, respectively. The second part of the study was an open dose-finding and drug safety study of a further 3 months in duration. The aim was to evaluate the efficacy and tolerance of 20, 30 and 40 micrograms. doses. All 47 patients who relapsed during the post-treatment period in part 1 were included. During this period 53% of the patients responded fully, 19% were intermediate responders and 28% did not respond. As reported in other studies most patients suffered relapse after treatment. During continued treatment for 3 months at doses between 20 and 40 micrograms. desmopressin was well tolerated, had no effect on body weight or blood pressure and did not cause any adverse reactions.
There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials.