Long-term treatment of nocturnal enuresis with desmopressin intranasal spray. 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. Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis. Desmopressin in nocturnal enuresis. Desmopressin acetate in children with severe primary nocturnal enuresis. [Treatment of isolated nocturnal enuresis: alarm or desmopressin?]. [Results of a therapeutic strategy against monosymptomatic nocturnal enuresis]. Desmopressin in nocturnal enuresis.
The purpose of this study was to determine the efficacy and safety of long-term treatment of nocturnal enuresis with desmopressin intranasal spray. Sixty-five children with primary nocturnal enuresis with a mean age of 11.3 years (range 7-17) underwent a 2-week observation period followed by dose titration period of 1 week. Those children completely dry with desmopressin entered a randomized, placebo-controlled, double-blind phase lasting 2 weeks, followed by a 6-month open treatment. The enuretic status of the children was documented for 2 weeks after the treatment was stopped. Eleven children had no change from baseline wetting with desmopressin. Thirty-two children receiving 20 mg and 9 children with 40 mg desmopressin were completely dry. Thirteen children were wet 1-2 nights per week, which was better than in the pretreatment period. During the 6-month open-treatment period, the effect of desmopressin was found to be stable. No side effects or adverse reactions were encountered. Two weeks after the treatment was stopped, 25 children were still completely dry (38% of the initial study population, 50% of the responders). The cure rate appeared to continue beyond 18 months after discontinuation of the treatment. 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. 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. Desmopressin acetate, a synthetic antidiuretic drug, was evaluated in two US multicenter studies involving a total of 176 children with severe primary nocturnal enuresis. Patients who qualified during the screening period, entered a double-blind treatment phase during which they received 20 micrograms or 40 micrograms of desmopressin acetate or placebo at bedtime for four weeks. This phase was followed by a four-week open-label period, during which all patients received 20 or 40 micrograms of desmopressin acetate. In both studies, children given desmopressin acetate had significantly fewer wet nights after two and four weeks of therapy than did children given placebo. During the open-label period, patients crossed over from placebo to desmopressin acetate showed similar reductions in enuresis. Global evaluations by the patients, their parents, or the investigators further confirmed the good results with desmopressin acetate. No serious adverse experiences were reported. Thus the results of these studies corroborate previously published reports of the efficacy and safety of desmopressin acetate in the treatment of primary nocturnal enuresis. 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. 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. The response of desamino-D-arginine vasopressin (DDAVP) was investigated in 32 enuretic children in a double-blind clinical study. The 15 children treated with DDAVP showed a significant reduction in the incidence of bed wetting--from 18.7 +/- 6.5 to 6.5 +/- 9.2 wet nights per 30 days. In 6 children bed wetting stopped entirely, in 6 there was a satisfactory response, and in 3 the response was marginal or there was none. When DDAVP was stopped most children reverted to their earlier bedwetting habits (15.7 +/- 8.9 nights a month). Response to DDAVP was significantly better in children aged more than 10 years (mean age for the entire group). The administration of DDAVP was not associated with any appreciable change in morning urine osmolalities. No adverse effects were noted. It is concluded that DDAVP is effective in nocturnal enuresis, particularly in older children. It is suggested that the cessation of bed wetting may, in part, reflect functional properties of DDAVP rather than antidiuresis.
Although tricyclics and desmopressin are effective in reducing the number of wet nights while taking the drugs, most children relapse after stopping active treatment. In contrast, only half the children relapse after alarm treatment. Parents should be warned of the potentially serious adverse effects of tricyclic overdose when choosing treatment. Further research is needed into comparisons between drug and behavioural or complementary treatments, and should include relapse rates after treatment is finished.