Oral desmopressin: a randomized double-blind placebo controlled study of effectiveness in children with primary nocturnal enuresis. The efficacy and safety of oral desmopressin in children with primary nocturnal enuresis. Desmopressin in the management of nocturnal enuresis in children: a double-blind study. Long-term treatment of nocturnal enuresis with desmopressin intranasal spray. Desmopressin in nocturnal enuresis. Desmopressin tablets in the treatment of severe nocturnal enuresis in adolescents. Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis. Desmopressin in nocturnal enuresis. A comparison of amitriptyline, vasopressin and amitriptyline with vasopressin in nocturnal enuresis.
Desmopressin nasal spray has proved to be efficacious treatment of primary nocturnal enuresis. Oral desmopressin tablets would be a more easily used, convenient vehicle for our patients and their parents. We evaluated the effectiveness of oral desmopressin in decreasing the number of wet nights in patients with primary nocturnal enuresis.
                We performed a double-blind, placebo controlled, parallel group trial of oral desmopressin in 141 children 5 to 17 years old with documented primary nocturnal enuresis at 14 sites. Patients were screened for number of wet nights for 2 weeks before study entry. A minimum of 3 wet nights weekly for 2 consecutive weeks was required for study entry. Patients were randomized to receive 200, 400 or 600 mcg. desmopressin or placebo before bedtime. Fluids were restricted 2 hours before bedtime based on body weight. The primary efficacy variable was mean decrease in the number of wet nights recorded during the last 2-week treatment period. The percentage of responding patients and mean decrease from baseline in number of wet nights at 2, 4 and 6 weeks were also assessed.
                The decrease in wet nights was 9, 20, 30 and 36% for placebo, and 200, 400, and 600 mcg. desmopressin orally per day, respectively. The 600 mcg. dose of oral desmopressin daily was statistically significantly different (p < 0.05) from placebo in decreasing wet nights. A complete or near complete response (0 to 2 wet nights) was noted in 3, 18, 33 and 24% of the patients who received placebo, and 200, 400 and 600 mcg. oral desmopressin daily, respectively. The 400 and 600 mcg. treatment groups were statistically significantly different (p < 0.05) from placebo. A less than 50% decrease in wet nights was noted in 83, 79, 64 and 61% of the patients who received placebo, and 200, 400 and 600 mcg. oral desmopressin daily, respectively. Oral desmopressin exhibited a dose response in the treatment of primary nocturnal enuresis. The linear trend for the decrease in wet nights was statistically significant (p < 0.05).
                A dose of 600 mcg. oral desmopressin daily significantly decreased the mean number of wet nights when administered for 6 weeks. A higher dose may be necessary for an improved response. We confirmed findings that oral desmopressin safely decreases the number of wet nights in children with enuresis and identified doses at which acceptable responses can be obtained.
                We evaluated the safety and efficacy of oral desmopressin in a double-blind, placebo controlled, parallel group, randomized, multicenter trial of 193 children 6 to 16 years old with documented primary nocturnal enuresis. The study was conducted in 2 phases: 1) a 2-week dose ranging phase in which children received desmopressin (0.2, 0.4 or 0.6 mg.) or placebo at bedtime and 2) an 8-week dose titration phase that followed a 2-week placebo washout. Patients received 0.2 mg. desmopressin or placebo for the first 2 weeks and then the dose was increased in 0.2 mg. increments at 2-week intervals until the patient was completely dry or was receiving 0.6 mg. Patients were instructed to limit fluid intake. Mean decrease from baseline in the number of wet nights, percentage of responding patients and safety were assessed at 2-week intervals.
                There was a statistically significant linear response to oral desmopressin at doses from 0.2 to 0.6 mg. during the dose ranging phase (p < or =0.05). The decrease in wet nights after 2 weeks of treatment with desmopressin was 27%, 30% and 40% at 0.2, 0.4 and 0.6 mg. doses, respectively, compared to 10% with placebo. All doses were statistically significantly different from placebo (p < or =0.05). During the dose titration phase all placebo treated and 87% of desmopressin treated patients were receiving the maximum dose of 3 tablets nightly because they had not been completely dry in the previous 2 weeks. Nevertheless, 44% of desmopressin treated patients had achieved at least a 50% reduction from baseline in the number of wet nights per 2 weeks at the lower doses of 0.2 and 0.4 mg. Most adverse events (rhinitis, pharyngitis, headache and increased cough) were mild to moderate in severity, unrelated to treatment and resolved before the study was completed.
                Oral desmopressin administered at bedtime to children with primary nocturnal enuresis was significantly better than placebo for decreasing episodes of bed-wetting (p <0.05). A linear dose-response relationship was observed (p <0.05). An acceptable response to treatment (50% or greater reduction from baseline in wet nights per 2 weeks) was seen at all doses of desmopressin. Oral desmopressin, up to 0.6 mg. for 8 weeks, was well tolerated. 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. 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. 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. 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. 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 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. 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.
Desmopressin rapidly reduced the number of wet nights per week experienced by children, but the limited evidence available suggested that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects during treatment, but that alarms may produce more sustained benefits. However, based on the available limited evidence, these conclusions are only tentative. Children should be advised not to drink more than 240 ml (8 ounces) of fluid during the evening before desmopressin treatment in order to avoid the possible risk of water intoxication.