[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. Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial. Primary nocturnal enuresis: a new approach to conditioning treatment. Desmopressin and imipramine in the management of nocturnal enuresis: a multicentre study. Prospective randomized trial using laser acupuncture versus desmopressin in the treatment of nocturnal enuresis. Treatment of nocturnal enuresis with an ultrasound bladder volume controlled alarm device. Desmopressin in the management of nocturnal enuresis in children: a double-blind study. Desmopressin acetate in children with severe primary nocturnal enuresis. Behavioral and self-concept changes after six months of enuresis treatment: a randomized, controlled trial. Desmopressin response of enuretic children. Effects of age and frequency of enuresis. Desmopressin resistant enuresis: pathogenetic and therapeutic considerations. A controlled trial of desmopressin and behavioral therapy for nocturnal enuresis. DDAVP and urine osmolality in refractory enuresis. [Enuresis nocturna in school children in Bodö. A therapeutic trial with a vasopressin analog: desmopressin and imipramine]. A comparison of amitriptyline, vasopressin and amitriptyline with vasopressin in nocturnal enuresis. Combination therapy of imipramine with oxybutynin in children with enuresis nocturna. A controlled comparison of two treatments for nocturnal enuresis. Nocturnal enuresis: a placebo controlled trial of two antidepressant drugs. Desmopressin has an influence on the arousability of children with primary nocturnal enuresis. A comparison of two enuresis alarms. Nocturnal enuresis: correction of renal function by desmopressin and diclofenac. Desmopressin tablets in the treatment of severe nocturnal enuresis in adolescents.
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. Desmopressin is an approved medical therapy for the treatment of monosymptomatic primary nocturnal enuresis. In cases of limited response to desmopressin, we have added anticholinergic therapy to desmopressin (combination therapy). To evaluate this treatment strategy, we examined the efficacy of combination therapy for primary nocturnal enuresis in desmopressin-nonresponders.
                Only patients with primary nocturnal enuresis refractory to the maximal dosage of desmopressin were enrolled. Children with lower urinary tract symptoms or bowel dysfunction were excluded, on the basis of a 3-day, 24-hour, frequency-volume chart and elimination record. Children continued to take desmopressin and were assigned randomly, in a double-blind manner, to receive either extended-release anticholinergic medication or placebo. Patients were reassessed after 1 month of therapy, with a 1-week nocturnal record.
                Forty-one desmopressin-nonresponders were enrolled, and 7 patients were excluded because of noncompliance. The treatment groups were equally matched with respect to age, gender, functional bladder capacity, and number of wet nights per week. After 1 month of treatment, there was a significant reduction in the mean number of wet nights in the combination therapy group, compared with the placebo group. With a generalized estimating equation approach, there was a significant 66% decrease in the risk of a wet episode, compared with the placebo group.
                This study represents the first prospective, placebo-controlled trial examining the effect of desmopressin in combination with long-acting, anticholinergic, bladder-relaxing therapy for monosymptomatic primary nocturnal enuresis. Conditioning treatment is the most effective therapy for nocturnal enuresis, precluding the use of drugs. An ordinary alarm clock can be used as an enuresis alarm. We sought to assess its clinical utility as a new means of conditioning treatment.
                Using the ordinary home alarm clock, 125 enuretic children were enrolled into two treatment groups. Group I included 70 children who set the alarm so as to get up and void in the toilet at a critical time when the bladder was full and they were still dry. Group II included 55 children who used the alarm to be awakened for voiding after 2 to 3 hours of sleep regardless of whether they were dry or wet. All children were motivated to use the alarm clock continuously for 4 months.
                Initial success was achieved in 54 (77.1%) of 70 group I and 34 (61.8%) of 55 group II children. Three months after treatment was stopped, success was still maintained in 46 (65.7%) and 31 (56.4%) children in groups I and II, respectively, but dropped to 41 (58.6%) and 29 (52.7%), respectively, after 6 months. The relapse rate after 3 and 6 months was 14.8% and 24.1% for group I and 8.8% and 14.7% for group II, respectively.
                The ordinary alarm clock performs as well as currently used enuresis alarms. It is an effective, elective, noncontact alarm that does not wait for bedwetting to initiate a conditioning reflex. It is both reliable and safe. The efficacy and safety of desmopressin (Minirin/DDAVP) treatment compared with imipramine were investigated in a multicentre, open, cross-over design in 57 patients, aged 6-15 years, affected by nocturnal enuresis to establish the best therapeutic approach to this condition. After a two-weeks observation and control period, patients were randomised to one of two groups: intranasal administration of desmopressin, 30 micrograms/day for three weeks, followed by imipramine, 0.9 mg/kg for a further three weeks, or imipramine 0.9 mg/kg for three weeks, followed by desmopressin, 30 micrograms/day for a further three weeks. Following treatment, all patients were observed for a further two weeks. Administration of either treatment protocol resulted in a statistically significant decline in the number of enuretic episodes per week compared to the control. The greater antidiuretic effect observed in the group receiving imipramine followed by desmopressin suggests the two compounds have different profiles. Also, when the treatment period was compared with the follow-up, the antidiuretic effect had a longer duration in the group initially given imipramine. No further improvement was seen when desmopressin was administered first, with a mild worsening of the effect sometimes occurring, suggesting a different carry-over effect between the two treatments. This suggests that desmopressin offers a better approach to the management of nocturnal enuresis. Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available, but desmopressin is a well-established option. On the other hand, alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents. To our knowledge, there is no prospective randomized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin.
                Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production. Then the children were randomized into two groups: group A children were treated with desmopressin alone, and group B children underwent laser acupuncture. All children were investigated after a minimum follow-up period of 6 month to evaluate the duration of the response.
                The children of both groups had an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up period of 6 months reevaluation revealed a complete success rate of 75% in the desmopressin-treated group. Additional 10% of the children had a reduction of their wet nights of more than 50%. On the other hand, 6 months after laser acupuncture, 65% of the randomized children were completely dry. Another 10% had a reduction of the enuresis frequency of more than 50% per week. 20% of the children in the desmopressin-treated group did not respond at all as compared with 15% in the acupuncture-treated group. Statistical evaluation revealed no significant differences among the response rates in both groups.
                Im comparison with pharmacological therapy using desmopressin, our study shows that laser acupuncture should be taken into account as an alternative, noninvasive, painless, cost-effective, and short-term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production. Success rates indicated no statistically significant differences between the well-established desmopressin therapy and the alternative laser acupuncture. Current treatment regimens for nocturnal enuresis are suboptimal. Medications such as desmopressin are efficacious for preventing the enuretic event but they offer little potential for a permanent cure and have side effects. Although the moisture alarm has good potential for a permanent cure, the child is mostly wet during treatment. Furthermore, the moisture alarm requires that the child make the somewhat remote association between the alarm event and a full bladder after the bladder has emptied. In this exploratory study bladder volume alarming, a new approach to treating nocturnal enuresis, was investigated.
                A total of 40 sequential children 6 to 16 years old with nonorganic nocturnal enuresis who had had at least 1 wetting episode weekly for greater than a year were divided into 2 groups. Each child wore a modified PCI 5000 miniature bladder volume measurement instrument during sleep. An alarm sounded when bladder volume reached 80% of the typical daytime voided volume in group 1 and at 80% of the typical enuretic volume in group 2. Group 2 patients also performed daytime bladder retention exercises in regard to instrument measured bladder volume versus a progressing target volume.
                In groups 1 and 2 the mean dryness rate before study initiation versus during the study was 32.9 and 9.3 versus 88.7 and 82.1%, respectively. Nighttime bladder capacity increased 69% in group 1 and 78% in group 2, while the cure rate was 55% (mean treatment period 10.5 months) and 60% (mean treatment period 7.2 months), respectively.
                Bladder volume tracking seems to approach the goals of ideal treatment for nocturnal enuresis in that it prevents the enuretic event, appears to facilitate a permanent cure and is noninvasive. Desmopressin (1-desamino-[8-D-Arg]-vasopressin) (DDAVP) was given by nose drops to 22 children with persistent nocturnal enuresis (mean age, 6.6 +/- 2.9 years; range, 4 to 12 years) the evening before sleep. With saline alone as placebo and with comparison to enuretic frequency before the onset of the trial, fortnightly periods were compared under double-blind conditions with the children at home. Pretreatment and placebo fortnights showed wetting frequencies (nights per fortnight) of 10.6 +/- 4.9 and 11.0 +/- 4.4, respectively. The value of the fortnight during desmopressin therapy was 4.2 +/- 4.5, which was significantly different from either of the previous means (P less than .01). Of the 22 subjects, four failed to react to therapy at all. There was decreased enuretic frequency in the remaining 18, of whom 12 decreased markedly or ceased wetting. One month after the trial, seven of the respondents were dry with desmopressin therapy. There was clear evidence of a large nocturnal volume of dilute urine before treatment in six of the respondents in whom such measurements could be reliably made. These children responded to dehydration with urine concentration, however, so that the suggestion can be made that a failure to develop a normal diurnal pattern of urine volume and concentration may underly some cases of enuresis. 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. Previous studies have suggested changes in self-concept with successful treatment of primary nocturnal enuresis (PNE), but behavioral changes have not been reported as a consistent associated finding.
                To determine if self-concept and behavior change after 6 months of treatment of monosymptomatic PNE by conditioning alarm or desmopressin acetate (DDAVP).
                Randomized, controlled trial in an inner-city hospital clinic. Subjects were 182 children referred or recruited through media publicity, randomly assigned both to 1 of 8 pediatricians and 1 of 3 treatment groups (alarm, DDAVP, or placebo). Included were children >7 years old with PNE, no daytime symptoms, bladder capacity >50% expected, and wetting >3 times a week. Excluded were children with central nervous system disorders or developmental delays, and those currently on DDAVP or alarm. Subjects completed the Piers-Harris Children's Self-Concept Scale and Harter's Perceived Competence Scale for Children (PCSC) at initial visit and after 6 months of treatment. Parents completed the Achenbach Child Behavior Checklist (CBCL) at the same times.
                After 6 months of treatment the Piers-Harris total score showed a highly significant treatment by period interaction effect for DDAVP, a significant effect for alarm, and no effect for placebo. For children who achieved 75% dryness the CBCL showed a treatment by improvement interaction effect that was highly significant for DDAVP and placebo with no effect for alarm. For the PCSC there were no treatment or outcome interaction effects. After 6 months of treatment there were significant changes over time unrelated to outcome or treatment in the Piers-Harris Subscales and in the CBCL Internalizing and Externalizing Scores, and the Social Thought and Attention Problems Subscales. The PCSC was more stable with no changes in total score, and positive changes over time in only 2 Subscales, Scholastic and Social.
                Children's self-concept improved with the type of treatment and amount of success. Parents' perceptions of behavior improve with type of treatment and amount of success. Children rate their self-concept and some physical attributes better after treatment with any of DDAVP, alarm, or placebo regardless of outcome. Frequent follow-up with emotional support and encouragement appear to be important components of an efficacious intervention for children with nocturnal enuresis. To characterize the children with enuresis likely to respond to desmopressin acetate, we performed a double-blind crossover study that included the use of a placebo. During the two weeks of desmopressin administration, six children (12%) had 13 or 14 dry nights, and 15 children (29%) had eight to 12 dry nights. Among the 17 children aged 9 years or older, with four to seven dry nights during the two-week baseline period, 12 children (71%) responded to desmopressin (eight to 14 dry nights). In contrast, none of the 15 children younger than 9 years of age with fewer than three dry nights before therapy responded. During the posttreatment period, only four of the 21 drug responders reported a persistent effect. Desmopressin may be effective in reducing the frequency of enuresis, especially in children older than 9 years of age without nightly enuresis. We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication.
                We gave 33 children with monosymptomatic nocturnal enuresis resistant to the standard 0.4 mg. oral dose of desmopressin 0.4 and 0.8 mg. desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion. The time of enuresis or nocturia was documented. All 9 children who had at least 1 dry treatment period during the randomized portion of the study then received open label treatment with 0.8 mg. desmopressin. Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment.
                Average time between bedtime and voiding was 5.0, 5.6 and 5.0 hours during the nights with placebo, and 0.4 and 0.8 mg. desmopressin, respectively (p = 0.12). Of the 9 children subsequently treated with 0.8 mg. desmopressin 5 became completely dry. Of the remaining 28 children given anticholinergic treatment 20 responded.
                Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis. This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability. A subgroup of enuretic children responds to high but not normal doses of desmopressin. The combination of desmopressin (DDAVP) and behavioral therapy for treatment of nocturnal enuresis was compared with use of each of these modes alone. We randomly assigned 226 enuretic children being treated in primary care clinics of a major medical center in the largest health maintenance organization in Israel into 3 groups: Group A) DDAVP plus behavioral therapy (double-blind); Group B) behavioral therapy plus placebo (double-blind); and Group C) DDAVP alone (open group). DDAVP (20 micrograms/naris) and placebo were administered by intranasal spray. Both pharmacologic and behavioral therapy were initiated after a 2-week observation period and continued for 8 weeks. All patients were followed for 2 months after completion of treatment. A significant reduction in the number of wet nights/week was registered for all 3 groups: 49% in Group A, 45% in Group B, and 19% in Group C. After controlling for confounding factors, no significant difference in effect was noted among the 3 types of treatment during the trial period. However, on follow-up the results for the DDAVP patients were significantly less stable compared with the other 2 groups (p = 0.015). Minor side effects were registered, but none of the participants withdrew from the trial. To our knowledge, this is the largest randomized trial of nocturnal enuresis conducted to date. Our findings suggest that simply discussing the problem with the patient and family leads to improvement, and that behavioral therapy is also beneficial. DDAVP can help, but the relapse rate on discontinuation is high. A double blind crossover trial of 20 micrograms intranasal 1-deamino-8-d-arginine vasopressin (DDAVP) versus placebo was carried out in 17 children with intractable enuresis aged between 6 and 13 years who had failed to respond to drugs and an enuresis alarm. Fluid intake was not restricted. There was a significant reduction in the number of wet nights. Seven children (41%) were cured or showed considerable improvement, with strong evidence against any placebo effect. The best response was seen in children aged 10 years or over and if urine osmolality after DDAVP reached beyond 1000 mmol/kg or was already at this concentration. The degree of overnight rise in urine osmolality after treatment with DDAVP was not predictable but correlated well with the clinical improvement in nocturnal diuresis present in eight of the children. A further 12 children with equally refractory enuresis were given 20 micrograms of the active drug to take during their school journeys or holidays. Six of them had previously normal overnight urine osmolalities with only two successes, but of the six who had nocturnal diuresis before treatment, five became dry, suggesting that DDAVP acts largely by anti-diuresis and might be most useful in children with nocturnal polyuria. nan Forty-five children aged 6-14 years with primary nocturnal enuresis were randomised to determine whether desmopressin is more effective than amitriptyline and whether the combination of amitriptyline/desmopressin is more effective than amitriptyline or desmopressin alone. Amitriptyline dosage was 25 mg for children 6-10 years and 50 mg for children aged 10-14 years. Desmopressin (20 micrograms) was given in the same dosage for all age groups. After a run-in period of 2 weeks, children were treated for 16 weeks and then observed for 12 weeks. In the amitriptyline group mean wet nights per week decreased from 5.8 +/- 0.9 to 3.3 +/- 1.9 (P < 0.0005); in the desmopressin group mean wet nights per week decreased from 6.0 +/- 0.9 to 4.7 +/- 1.7 (P < 0.02); in the amitriptyline/desmopressin group mean wet nights per week decreased from 6.3 +/- 0.9 to 3.3 +/- 2.5 (P < 0.0006). When comparing the groups, amitriptyline/desmopressin and amitriptyline were statistically more effective than desmopressin in week 6 (P < 0.009), week 8 (P < 0.03) and week 10 (P < 0.04). No significant side effects occurred. At this dose amitriptyline was more effective than desmopressin and the combination of desmopressin and amitriptyline did not confer any additional benefit. The treatment approach for enuresis is controversial due to the lack of consensus as to the exact causes of nocturnal enuresis. Despite various treatment modalities, pharmacotherapy still appears to be the common choice. The aim of this prospective study was the evaluation of the efficacy of combination therapy (imipramine and oxybutynin) in patients with enuresis nocturna.
                This prospective study was done with 77 monosymptomatic nocturnal enuretics between July 1996 and December 1998.
                Even though there is no statistically significant difference between combination therapy (imipramine plus oxybutynin) and monotherapy, clinical data showed that combination therapy is more effective.
                We conclude that combination of imipramine with oxybutynin is a safe and new choice in the treatment of nocturnal enuresis.
                Copyright 2000 S. Karger AG, Basel This study assessed change in the frequency of primary nocturnal enuresis as produced by either behavioral conditioning with a urine alarm, pharmacotherapy with imipramine hydrochloride, or assignment to a clinical waiting list. The study also investigated the effect of treatment method and outcome on subjects' level of emotional and behavioral adjustment. An attempt was made to identify pretreatment predictors of treatment outcome and premature withdrawal from the treatment program. The results indicated a significantly more effective outcome for the conditioning approach. Comparison of pre- and post-treatment measures of adjustment provided insufficient evidence to support the hypotheses that either change in the frequency of nighttime wetting or the method of treatment received would influence the subject's level of emotional and behavioral adjustment. The enuresis tolerance scale was found to be a highly significant predictor of early termination from conditioning treatment. A multicentre, randomised, double blind treatment trial was set up comparing imipramine (a tricyclic antidepressant with anticholinergic action), mianserin (a quadricyclic antidepressant without anticholinergic activity), and placebo, (a) possibly to identify an effective alternative drug and (b) to elucidate the action of imipramine in enuretic children. Eighty children (65 boys, 15 girls) aged 5-13 years, wet three or more nights a week, were studied. Exclusions were a urinary tract infection or abnormality, other organic illness, or severe emotional disorders. After a four week assessment, 25 children were randomised to eight weeks' treatment with imipramine 25 mg, 26 to mianserin 10 mg and 29 to placebo, followed by four weeks without treatment. Dry nights and a wetness score were recorded throughout. During treatment, imipramine was superior to both placebo and mianserin (p < 0.001) in achieving dry nights and reducing wetness scores. It led to a definite improvement in 72% of children. Mianserin produced a mildly beneficial effect that was not superior to placebo. No side effects were recorded. Mianserin would not be a satisfactory alternative treatment for nocturnal enuresis. The efficacy of imipramine is unlikely to be the result of its antidepressant activity. Several studies provide evidence regarding the effect of desmopressin (DDAVP) on the sleep of adults. Therefore, we investigate whether this effect has a role in children with primary nocturnal enuresis treated intranasally with DDAVP.
                A prospective, randomized, placebo controlled, double-blind, crossover study was performed. Patients were assigned to 2 groups by lottery. Arousability was determined by a special bell apparatus with an adjustable sound pressure level. The wet nights per week and the results of the arousal tests were compared using the signed rank test.
                A total of 20 children with primary nocturnal enuresis 6 to 15 years old were enrolled in the study, 2 of whom had to be excluded. There were no marked differences in age or weight between the groups. The number of wet nights per week decreased significantly with DDAVP treatment. Moreover 14 patients slept more soundly with DDAVP and only 4 were more difficult to awake after the medication. This difference was significant.
                This study revealed an effect of DDAVP on arousability of enuretic children as well as its previously known action for the treatment of primary nocturnal enuresis. This result is consistent with the known action of DDAVP on sleep of elderly adults. It suggests that the cause of primary nocturnal enuresis lies in the structure of sleep of the affected patients. This randomized experiment was undertaken to determine if any difference in success occurred between an audio versus a vibration alarm for nocturnal enuresis. Similar rates of success were achieved for 47 children, aged 6 to 12 years, who partially or totally completed the 3-month period of alarm use. Sixty-two children with nocturnal enuresis (43 boys, 19 girls aged 6-15 years) were treated with either desmopressin (Adiuretin-SD) (n = 32) or sodium diclofenac (n = 30). Desmopressin was effective in 85% of children and diclofenac in 33%. In children with primary nocturnal enuresis, the glomerular filtration rate was normal, whereas diuresis and solute excretion during the night were increased. Compared with healthy children, the nightly excretion of sodium was elevated by 43.7% and magnesium by 58.4%. A high correlation was found between the free water reabsorption and solute clearance (P < 0.001) in children with nocturnal enuresis. Changes in kidney function in nocturnal enuresis appear to be due to a decrease in the water and ion reabsorption in the thick ascending limb of Henle's loop because of a changed regulation of ion transport in this part of the nephron. Administration of desmopressin or a decrease in prostaglandin production after diclofenac administration restores the ion and water transport in the kidney, which results in the disappearance of nocturnal enuresis. The results indicate a role of changes in regulation of ion transport in renal tubules in the pathogenesis of one of the forms of primary nocturnal enuresis. In recent years the treatment of primary nocturnal enuresis (PNE) with desmopressin (DDAVP) has been promising. The route of administration until now had been intranasal, but because the tablets were introduced for the treatment of diabetes insipidus they have also become available for the treatment of PNE.
                To find the optimal dosage of desmopressin tablets and to compare desmopressin's efficacy with placebo in a group of adolescents with severe monosymptomatic enuresis. The long-term safety of desmopressin was also studied in the same group of patients.
                The effect of oral desmopressin (1-deamino-8-D-arginine-vasopressin) (DDAVP tablets, Minirin) was investigated in 25 adolescents (ages 11 to 21 years) with severe monosymptomatic nocturnal enuresis. The first part of the dose-ranging study comprised a single-blind dose titration period, followed by a double-blind, crossover efficacy period comparing desmopressin with placebo. The final part was an open long-term study consisting of two 12-week treatment periods. The efficacy of the drug was measured in reductions of the number of wet nights per week.
                During the first dose-titration period, the majority of the patients were given desmopressin 400 micrograms, and the number of wet nights decreased from a mean of 4.9 to 2.8. During the double-blind period, a significant reduction of wet nights was observed (1.8 vs 4.1 for placebo). During the two long-term periods, 48% and 53% of the patients could be classified as responders (0 to 1 wet night per week) and 22% and 23.5% as intermediate responders (2 to 3 wet nights per week). No weight gain was observed due to water retention. After cessation of the drug, 44% of the patients had a significant decrease in the number of wet nights.
                Oral desmopressin has a clinically significant effect on patients with PNE, and therapy is safe when administered as long-term treatment.
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.