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At least 19 recordsLinked to original sources

PubMed2000

Desmopressin for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. OBJECTIVES: To assess the effects of desmopressin on nocturnal enuresis in children, and to compare desmopressin with other interventions. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials of desmopressin for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive desmopressin compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were reported. Trials focused solely on daytime wetting were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: Twenty one randomised trials involving 948 children treated with desmopressin, met the inclusion criteria. The quality of many of the trials was poor. Desmopressin was compared with a tricyclic drug in two trials, and with alarms in one. Desmopressin was effective in reducing bedwetting in a variety of doses and forms. Each dose of desmopressin reduced bedwetting by at least one night per week during treatment (eg 20microg: 1.56 fewer wet nights per week, 95% CI -1.94 to -1.19). Participants on desmopressin were 4.6 times more likely to achieve 14 consecutive dry nights (95% CI 1.38 to 15.02) compared with placebo. However, there was no difference after treatment was finished. There was no apparent dose-related effect of desmopressin, but the evidence was limited. Data which compared oral and nasal administration were too few to be conclusive. Desmopressin and imipramine (a tricyclic drug) were equally effective in one small trial. Amitriptyline (another tricyclic) was not consistently better than desmopressin either alone or when used as a supplement. In a single trial, desmopressin was initially superior to using an alarm in reducing the number of wet nights per week: WMD -1.7 (95% CI: -2.96 to -0.45), but this result was not sustained; after three months of treatment, patients using the alarm had 1.4 fewer wet nights per week than with desmopressin: (95% CI: 0.14 to 2.65). Participants receiving the alarm intervention were also nine times less likely to relapse than those given desmopressin: RR 9.2 (95% CI: 1.28 to 65.9). Combining alarm and drug therapy was found to be superior to alarm treatment alone. The addition of desmopressin to an alarm schedule resulted in one less wet night per week: (95% CI: -1.55 to -0.45). REVIEWER'S CONCLUSIONS: Desmopressin rapidly reduced the number of wet nights per week, but there was some evidence that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects, but that alarms produced more sustained benefits. However, based on the available evidence, these conclusions can only be tentative. There was some evidence of minor side effects of desmopressin in the included trials, such as nasal irritation and nose bleeds. However, the risk of water intoxication associated with over-drinking before bedtime has been reported. Patients and their families need to be warned of potential adverse effects and advise

Child↗

PubMed2005

The pharmacokinetics of 400 microg of oral desmopressin in elderly patients with nocturia, and the correlation between the absorption of desmopressin and clinical effect.

OBJECTIVE: To investigate the pharmacokinetic profile of oral desmopressin in elderly patients with nocturia, and to analyse any possible correlation between the absorption and clinical effect. PATIENTS AND METHODS: In all, 32 patients were screened to determine the baseline number of nocturnal voids and the nocturia index; of these, 24 fulfilled the inclusion criteria and were enrolled for a pharmacokinetic evaluation of oral desmopressin 400 microg. A double-blind, randomized, placebo-controlled, crossover-effect evaluation period was then used to test the association between the absorption of desmopressin and pharmacodynamic effect. Serial plasma samples were collected for 8 h for a pharmacokinetic analysis of desmopressin. The pharmacodynamics after an equivalent oral dose before bedtime were assessed by measuring changes in the number of nocturnal voids, time to first nocturnal void and nocturnal diuresis, from placebo to active treatment. RESULTS: There was a linear relationship between plasma desmopressin at 2 h after dosing and the area under the plasma concentration curve from 0 to infinity (Pearson's rho 0.923, P < 0.001). Women had a significantly higher plasma desmopressin concentration than men (P = 0.0012) and more adverse events. There was no correlation between plasma desmopressin at 2 h after dosing and the within-patient response in any of the effect variables. Generally, the number of nocturnal voids and nocturnal diuresis were half that with placebo. The time to the first nocturnal void was almost doubled compared with placebo. CONCLUSIONS: There seems to be a relationship between gender, plasma level of desmopressin and the incidence of adverse events. Plasma desmopressin at 2 h after dosing cannot be used to predict the pharmacodynamic response, although desmopressin lowers the nocturnal diuresis and the number of nocturnal voids.

Absorption↗

PubMed2000

Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics).

BACKGROUND: Enuresis (bedwetting) is a socially unacceptable and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. OBJECTIVES: To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children, and to compare them with other interventions. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials of drugs (excluding desmopressin or tricyclics) for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive drugs compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were provided. Trials focused solely on daytime wetting were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: None of the drugs (phenmetrazine, amphetamine sulphate/ephedrine + atropine, furosemide (sic) or chlorprotixine) were better than placebo during treatment. The numbers were too small to draw reliable conclusions, and none are used in current practice in the UK. Imipramine (a tricyclic) was better than each of the three drugs with which it was compared (meprobamate, ephedrine sulphate and furosemide) even though the numbers were small. Alarm treatment was better than drugs in one small trial. REVIEWER'S CONCLUSIONS: There was not enough evidence to suggest that the included drugs reduced bedwetting. There was limited evidence to suggest that imipramine and alarms were better, and in other reviews, desmopressin, tricyclics and alarm interventions have tentatively been shown to be effective.

Child↗

PubMed2002

The desmopressin and combined CRH-desmopressin tests in the differential diagnosis of ACTH-dependent Cushing's syndrome: constraints imposed by the expression of V2 vasopressin receptors in tumors with ectopic ACTH secretion.

The role of desmopressin, alone or in combination with CRH, in the differential diagnosis between Cushing's disease (CD) and ectopic ACTH secretion (EAS) still remains uncertain. Based on existing data, the desmopressin test is regarded as an alternative to the CRH stimulation test and, when given in combination with CRH, it has been suggested to completely discriminate between patients with CD and EAS. However, assessment of these tests has been limited in only a small number of patients with EAS. Desmopressin is a relatively specific V2 vasopressin receptor (V2R) agonist. Although expression of V3 vasopressin receptor (V3R) is common in tumors with EAS, the expression of V2R has not been extensively investigated. In the present study, we report our findings of the desmopressin and the combined CRH-desmopressin test in a series of patients with CD and EAS; also, the expression of V2R and V3R was investigated in tumors with EAS by a RT-PCR method. We assessed a cohort of 31 patients with ACTH-dependent Cushing's syndrome, including 26 patients with CD and five cases with histologically confirmed EAS. To avoid bias of predetermined criteria, univariate curves of the receiver operating characteristics (ROC) were constructed by plotting the sensitivity against 1-specificity at each level of the percent cortisol (F) and ACTH responses to these tests. Following desmopressin administration there was an overlap of the percent F and ACTH responses among patients with CD and EAS, and the area under the ROC curve for both these responses was not significantly different than that occurring by chance. This was also true for the percent F response following the combined CRH-desmopressin test. However, the area under the ROC curve for the percent ACTH rise following the combined test was significantly different; the point of the ROC curve closest to 1 corresponded to a percent ACTH rise of 218% (88% sensitivity and 80% specificity). Expression of V2R and V3R mRNA was investigated in four of the five excised tumors with EAS and revealed the presence of the V2R in all, whereas the V3R mRNA was expressed in three of these cases. In conclusion, in this series the desmopressin test produced a significant overlap of responses between CD and patients with EAS and, therefore, is of limited value in the differential diagnosis of the ACTH-dependent Cushing's syndrome. This is most probably due to the expression of the V2R in tumors with EAS. Moreover, following the combined CRH-desmopressin test only the ACTH but not the F responses were diagnostically useful, but still far from completely discriminating patients with CD and EAS.

ACTH Syndrome, Ectopic↗

PubMed2005

Comparison of effects of treatment of primary nocturnal enuresis with oxybutynin plus desmopressin, desmopressin alone or imipramine alone: a randomized controlled clinical trial.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

PubMed2001

The limited value of the desmopressin test in the diagnostic approach to Cushing's syndrome.

OBJECTIVE: The desmopressin test is generally regarded as an alternative to the CRH test but it is unclear whether desmopressin is as effective as CRH in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, a precise assessment of the operating characteristics of the desmopressin test in comparison with the CRH test has not been reported. The aim of the present study was to make a comparative evaluation of desmopressin and CRH tests in a consecutive cohort of patients with ACTH-dependent Cushing's syndrome and in a group of healthy subjects. DESIGN AND SUBJECTS: We studied 34 patients with Cushing's disease (CD) and nine patients with ectopic ACTH syndrome (EAS). The control group included 30 healthy subjects. Estimates of sensitivity and specificity were determined for a value of ACTH percent increment (Delta%) > 35% and for a Delta % > 50%, following either desmopressin or CRH, to differentiate CD from EAS. The sensitivity and specificity of a composite rule requiring an ACTH net increment (Delta) > 4.5 pmol/l at both values of Delta % was also calculated. When evaluating cortisol responses, the criteria were Delta % > 20% and Delta > 193 nmol/l. Moreover, to allow comparison of individual end points of the desmopressin and CRH tests at multiple levels of Delta % or Delta either for ACTH or cortisol without the bias of predetermined criteria, univariate curves of the receiver operating characteristics (ROC) were constructed by plotting the sensitivity against 1 - specificity at each level. RESULTS: In the patients with CD, the frequency of ACTH response was of 90% after both tests while the figures for cortisol were 73% after CRH and 77% after desmopressin, respectively. In the 15 patients who underwent both tests the magnitude of ACTH and cortisol responses induced by the 2 stimuli were fully comparable. In the patients with EAS a (false) positive ACTH response was found in 2/9 cases (22%) after the CRH test and in 2/5 patients (40%) after the desmopressin test. In the healthy subjects the CRH test was performed in 25 cases and the desmopressin test in 15 cases. The frequency of ACTH response was 52% following CRH and 13% following desmopressin. In the 10 healthy subjects who underwent both tests the ACTH response was significantly greater after CRH than desmopressin. The area under the ROC curve for the ACTH Delta % was significantly different than that occurring by chance following CRH but not desmopressin. The point on the ROC curve closest to 1 corresponded to an ACTH Delta % of 47% (sensitivity 87% and specificity 89%). However, a criterion of 100 % specificity would require an increase in the threshold for the ACTH Delta % to 259%. ROC analysis validated also the use of the ACTH Delta as a method to assess the response to CRH, but not after desmopressin. However, the diagnostic performance of this parameter was reduced in comparison to that of the ACTH Delta %, since the best cut-off for the Delta (6.2 pmol/l) had inferior specificity (79%). The operating characteristics of CRH and desmopressin were worse when considering cortisol responses. CONCLUSIONS: The present data suggest that the CRH test is more reliable than the desmopressin test in determining the aetiology of Cushing's syndrome. The desmopressin test resulted in a high frequency of false positive results in patients with ectopic ACTH secondary to carcinoid tumours. This finding may be due to the capability of these tumours to express the V3 vasopressin receptor through which desmopressin acts. However, the clinical endocrinologist may be confronted with some disturbing cases which are misdiagnosed because it is almost impossible to set a diagnostic criterion providing complete specificity in the differentiation of (occult) ectopic Cushing's syndrome using either CRH or desmopressin tests.

ACTH Syndrome, Ectopic↗

PubMed2001

Desmopressin stimulation test before and after pituitary surgery in patients with Cushing's disease.

OBJECTIVE: The desmopressin test has been proposed as a useful tool for the differential diagnosis of Cushing's disease. The aim of our study was to investigate, in a large series of patients with Cushing's disease, the incidence of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated the test soon after surgery to verify its usefulness in the assessment of early and late surgical results. PATIENTS AND METHODS: One hundred and seven consecutive patients with Cushing's disease, 89 female and 18 male patients, with a mean age of 37.2 +/- 1.3 years, were studied. All patients, except three, repeated the test 5-6 days after surgery. Desmopressin (10 microg) was injected i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma ACTH and serum cortisol were measured in duplicate by commercially available immunoassays. A positive response to desmopressin was considered to be a plasma ACTH and serum cortisol increment of at least 30% and 20% above baseline, respectively. RESULTS: Mean basal plasma ACTH level was 17.3 +/- 1.7 pmol/l and rose to a peak level of 42.7 +/- 4.9 pmol/l at 15 minutes Mean basal serum cortisol level was 574 +/- 19 nmol/l and rose to a peak level of 814 +/- 28 nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely correlated with their respective basal levels. Ninety patients (84.1%) had an ACTH and 84 patients (78.5%) had a cortisol response to desmopressin. Several clinical and demographic characteristics were not significantly different among desmopressin responders and non responders, except that basal ACTH and cortisol levels were significantly higher in desmopressin non responders (27.2 +/- 8.3 pmol/l, 781 +/- 86 nmol/l) than in desmopressin responders (15.4 +/- 1.2 pmol/l, 535 +/- 14 nmol/l). Disappearance of the ACTH and cortisol response to desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57 of 81 (70.4%) cortisol responders, respectively. However, concordance between the desmopressin test and surgical outcome was not complete. Indeed, 18 patients considered in remission still showed an ACTH increase after desmopressin and, on the contrary, four patients with disappearance of the ACTH response had persistence of hypercortisolism. During follow-up monitoring, three patients, who had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54 months after surgery. CONCLUSIONS: Desmopressin administration elicits a significant rise in ACTH and cortisol levels in the majority but not all patients with Cushing's disease. There is a good, but not complete, concordance between the response to the desmopressin test and the surgical outcome. Our preliminary data show that persistence of the ACTH response to desmopressin in the early postoperative period might be associated with a higher risk of late relapse.

Adolescent↗

PubMed1998

Effect of food intake on the pharmacokinetics and antidiuretic activity of oral desmopressin (DDAVP) in hydrated normal subjects.

OBJECTIVE: The effect of food ingestion on the gastrointestinal absorption and antidiuretic action of oral desmopressin. An oral preparation of desmopressin, a synthetic analogue of vasopressin, has recently become available for clinical use. DESIGN: A randomized, single-blind, crossover study with four treatment arms. Day A, no meal + placebo; B, no meal + 400 micrograms oral desmopressin; C, standard meal + 400 micrograms oral desmopressin; D, standard meal + 400 micrograms oral desmopressin after 1.5 hours. Plasma desmopressin was measured every 15-30 minutes for 6 hours after drug intake. An intravenous hydration regimen was employed on each study day. SUBJECTS: Sixteen healthy, non-smoking, mean aged 20-35 years (mean 27.8 years). MEASUREMENTS: Plasma desmopressin concentrations were measured throughout each study day to calculate the area under the desmopressin plasma-concentration-time curve to infinity (AUCinf), the maximum plasma desmopressin concentration (Cmax), the time at which Cmax was reached (Tmax) and the time at which plasma desmopressin was first detected (Tlag). Urine volume, urine osmolality and plasma sodium concentrations were also measured at specified times on each study day. RESULTS: The total absorption of oral desmopressin, reflected by the AUCinf, was significantly higher when taken during the fasting state (day B) compared with its administration with or 1.5 hours after a standard meal (days C and D). In addition, Cmax was higher and both Tmax and Tlag were shorter on day B compared with days C and D. No effect of food ingestion was observed on the pharmacodynamics of oral desmopressin: urine volume was decreased and urine osmolality was increased to similar extents on all active treatment days (B, C and D). No significant reductions in plasma sodium concentrations (a safety parameter) was observed during the trial. CONCLUSIONS: The gastrointestinal absorption of desmopressin is reduced and delayed if administered with or 1.5 hours after a meal. This decreased absorption of desmopressin did not have an impact on the antidiuretic action of the drug since all treatment regimens elicted a maximal response. It is possible that administration of desmopressin in the fasting state may prolong its duration of action.

Administration, Oral↗

PubMed2003

Stability of desmopressin loaded in liposomes.

Desmopressin-containing liposome formulations have been developed for intranasal administration previously. Positively charged liposomes were found to be an efficient delivery system for desmopressin. In this study, stability of the loaded desmopressin in positively charged liposomes was further investigated. Comparison of the stability of desmopressin in solution and liposomes was made. Degradation of desmopressin was shown to follow a pseudo-first-order reaction. Degradation of desmopressin in both solution and liposomes demonstrated the same kinetic behavior and exhibited no significant difference in half-lives. Similar v-shape pH-rate profile was found for desmopressin degradation in solution and liposomes. At pH 4.0, the inflection point of the v-shape pH-rate curve, the reaction rate of desmopressin was lowest and the stability was greatest. The stability of lipid ingredients of dioleoylphosphatidylcholine (DOPC), cholesterol (C), and stearylamine (S) in the liposome dispersion at pH 4.0 was studied. Results demonstrated that DOPC, C, and S were relatively stable in the liposome structure when formulated with desmopressin. The degradation of desmopressin in solution and liposomes in the presence of alpha-chymotrypsin was investigated. A longer half-life for desmopressin in liposomes than in solution was observed. It was suggested that desmopressin was protected by the liposomes against alpha-chymotrypsin digestion.

Amines↗

PubMed1997

Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess.

OBJECTIVE: To assess the ability of desmopressin administration to stimulate ACTH/cortisol secretion in patients with Cushing's disease, either before or after surgery, and in patients with other states characterized by ACTH hypersecretion, and to compare the results with those obtained after CRH testing. DESIGN AND SUBJECTS: Plasma ACTH and serum cortisol levels were evaluated after the administration of desmopressin (10 micrograms i.v.), CRH (1 microgram/kg i.v.) and saline on different days in 17 patients with Cushing's disease, 1 with occult ectopic ACTH syndrome, 5 with Addison's disease, 3 who had been bilaterally adrenalectomized for Cushing's syndrome and 4 normal subjects. After pituitary adenomectomy desmopressin and CRH were administered again to 13 of the patients who had undergone pituitary surgery for their Cushing's disease. RESULTS: In 16 patients with Cushing's disease with microadenoma a positive ACTH/cortisol rise occurred in 11 patients after both desmopressin and CRH, 2 other patients were responsive only to desmopressin and 2 only to CRH, while in 1 patient equivocal responses to both tests were found. The persistence of a hormonal response to desmopressin after pituitary adenomectomy for Cushing's disease correlated with unsuccessful surgery, while, contrary to CRH, absent ACTH/cortisol rises were found in cured patients 1 and 12 months after operation. In 1 patient suspected for ectopic ACTH hypersecretion, desmopressin and CRH administration did not cause any ACTH/cortisol rise. Significant ACTH rises occurred after both desmopressin and CRH testing in patients with Addison's disease. All the 3 patients adrenalectomized for Cushing's syndrome showed a rise of ACTH levels after CRH, while a similar response after desmopressin occurred in only one of them. CONCLUSIONS: Desmopressin is able to stimulate ACTH and hence cortisol release in Cushing's disease. It may be a useful test in patients with doubtful responses to CRH test, in those exhibiting responses to CRH indistinguishable from those of normal subjects and in the postoperative follow-up of Cushing's disease. In some patients with abolished or reduced cortisol feed-back at hypothalamic-pituitary level the sensitivity of normal corticotrophs to desmopressin is enhanced.

ACTH Syndrome, Ectopic↗

PubMed2001

The efficacy and safety of oral desmopressin in children with primary nocturnal enuresis.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Administration, Oral↗

PubMed1997

Oral desmopressin: a randomized double-blind placebo controlled study of effectiveness in children with primary nocturnal enuresis.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Administration, Oral↗

PubMed1998

Administration of desmopressin in brain-dead donors and renal function in kidney recipients.

BACKGROUND: Diabetes insipidus is common among brain-dead donors and may lead to decreased graft function. The use of desmopressin to limit the consequences of diabetes insipidus is controversial. We assessed the effects of desmopressin administered to brain-dead donors on early and long-term graft function in kidney recipients. METHODS: In a randomised controlled study, 97 brain-dead donors received desmopressin as 1 microg bolus every 2 h when diuresis was more than 300 mL/h (desmopressin group n=49) or no desmopressin (control group n=48). In 175 kidney recipients (controls n=89, desmopressin group n=86) we measured serum concentrations of creatinine and haemodialysis requirements to assess early renal function in the first 15 days after transplantation. We assessed long-term results of transplantation (median time 45 months) for a homogeneous subgroup of 95 recipients (48 in the desmopressin group). FINDINGS: We found no significant differences between the two groups of brain-dead donors, except for final diuresis, which was lower in the desmopressin group than among controls. Haemodialysis requirement in controls and the desmopressin group (20 vs 23%, p=0.63) and serum creatinine concentrations (decrease from 903 micromol/L to 206 micromol/L vs 814 micromol/L to 193 micromol/L, p=0.14) did not differ significantly in the first 15 days after transplantation. Long-term graft survival was similar in the two groups (88 vs 87%). INTERPRETATION: Desmopressin can be given to brain-dead donors to limit the harmful effects of diabetes insipidus without any substantial effects to graft function in recipients.

Adult↗

PubMed2002

Effects of desmopressin on thrombogenesis in aspirin-induced platelet dysfunction.

Aspirin causes a coagulation disorder. Desmopressin has haemostatic effects by increasing the plasma levels of coagulation factor VIII and von Willebrand factor. The precise effects of desmopressin on thrombogenesis are not known. In an in vivo model, we investigated the effect of the drug on thrombus formation and platelet function after aspirin use. Male Lewis rats weighing 250-300 g were used. Four groups with 10 animals each were formed: control, aspirin, desmopressin and aspirin + desmopressin. In each animal, the femoral artery was dissected. A thrombogenic vessel injury was created by inverting a full thickness portion of the proximal edge of the incised artery into the lumen. The following parameters were measured: maximum thrombus size, time period until maximum thrombus size was reached and overall platelet function. In addition, the thrombi generated were investigated histologically. Thrombus formation time was significantly shorter with desmopressin compared with the animals treated with aspirin (P < 0.0001) and controls (P = 0.008). Maximum thrombus size was larger in the desmopressin and desmopressin + aspirin groups when compared with the group treated with aspirin only. Overall platelet function was significantly enhanced with desmopressin compared with controls (P = 0.025) and with aspirin (P < 0.0001). The differences were confirmed histologically. In conclusion, desmopressin significantly accelerates thrombus formation in aspirin-treated animals. It can also re-establish thrombus size after the use of aspirin. Overall platelet function is significantly increased by desmopressin.

Animals↗

PubMed2002

Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo-controlled study in men.

OBJECTIVE: To investigate the efficacy and safety of oral desmopressin in the treatment of nocturia in men. PATIENTS AND METHODS: Men aged >/=18 years with verified nocturia (>or=two voids/night) and nocturnal urine production greater than their maximum functional bladder capacity were recruited. A 3-week dose-titration phase established the optimum desmopressin dose (0.1, 0.2 or 0.4 mg). After a 1-week 'washout' period, patients who responded in the dose-titration period were randomized to receive the optimal dose of desmopressin or placebo in a double-blind design for 3 weeks. RESULTS: In all, 151 patients entered the double-blind period (86 treated with desmopressin, 65 with placebo). In the desmopressin group 28 (34%) patients and in the placebo group two (3%) patients (P<0.001) had fewer than half the number of nocturnal voids relative to baseline; the mean number of nocturnal voids decreased from 3.0 to 1.7 and from 3.2 to 2.7, respectively, reflecting a mean decrease of 43% and 12% (P<0.001). The mean duration of the first sleep period increased by 59% (from 2.7 to 4.5 h) in the desmopressin group, compared with an increase of 21% (from 2.5 to 2.9 h) in the placebo group (P<0.001). The mean nocturnal diuresis decreased by 36% (from 1.5 to 0.9 mL/min) in the desmopressin group and by 6% (from 1.7 to 1.5 mL/min) in the placebo group (P<0.001). The mean ratio of night/24-h urine volume decreased by 23% and 1% (P<0.001), and the mean ratio of night/day urine volume decreased by 27% and increased by 3% (P<0.001) for the desmopressin and placebo groups, respectively. In the double-blind treatment period, similar numbers of patients had adverse events; 15 (17%) patients in the desmopressin and 16 (25%) patients in the placebo group. Most adverse events were mild. Serum sodium levels were <130 mmol/L in 10 (4%) patients and this occurred during dose-titration. CONCLUSIONS: Orally administered desmopressin is an effective and well-tolerated treatment for nocturia in men.

Administration, Oral↗

PubMed1999

Desmopressin treatment: current status.

Desmopressin has a proven pharmacological effect in most enuretic patients, although a clinical response is not seen in all patients. Numerous questions about the current treatment status of desmopressin include the specific anti-enuretic effect of desmopressin, the effect of desmopressin on sleep and the use of desmopressin as a possible cure for enuresis. The Swedish Enuresis Trial has produced some very positive results on the long-term use of desmopressin, showing a 61% response rate (> 50% reduction in wet nights). Desmopressin has proven to be highly effective when used in combination with other treatments, including the alarm and oxybutinin, and after urotherapy. It is suggested that imipramine should not be used to treat enuresis unless the patient has attention deficit hyperactivity disorder. Bladder instability is also an important factor to consider when selecting treatment for enuresis. Bladder dysfunction (detrusor overactivity) can be the cause of lack of clinical response to either desmopressin or alarm treatment; in such cases, following a cystometrogram, patients should be treated with detrusor-relaxing drugs, and urotherapy should be considered as the first treatment option. The most effective treatment for enuresis is the treatment chosen by the patient and their families. Desmopressin and urotherapy have had promising results, with desmopressin acting as a bridge until spontaneous or treatment-induced remission occurs.

Child↗

PubMed2000

Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing's disease.

OBJECTIVE: To evaluate the plasma ACTH and serum cortisol responses to desmopressin in patients with Cushing's disease either before or after pituitary adenomectomy during long-term follow-up, and to compare the results with those obtained after corticotrophin-releasing hormone (CRH) testing. DESIGN: Plasma ACTH and serum cortisol concentrations were evaluated after the administration of desmopressin (10 microg i.v.) or CRH (1 microg/kg i. v.) in 34 patients with Cushing's disease. Twenty-four patients with active Cushing's disease were evaluated both before and after transsphenoidal pituitary surgery (TSS); these patients were followed up for 1-36 months. Ten patients were studied only after a long-term period (1-19 years, median 4 years) after TSS (six patients), TSS plus external pituitary irradiation (three patients) and TSS plus radiosurgery (one patient). RESULTS: In 24 patients with active Cushing's disease a significant ACTH/cortisol response (P<0.001) was induced by either desmopressin (ACTH from a baseline of 15.3+/-2.7 pmol/l to a peak of 40.9+/-7.3 pmol/l; cortisol from 673+/-59 nmol/l to 1171+/-90 nmol/l) or CRH (ACTH from a basal of 14. 2+/-2.5 pmol/l to a peak of 47.2+/-7.7 pmol/l; cortisol from 672+/-50 nmol/l to 1192+/- 80 nmol/l). In all patients a positive cortisol response to desmopressin was found. After pituitary adenomectomy the 14 'cured' patients were followed up for 1-36 months; desmopressin administration never induced ACTH or cortisol responsiveness in any patient. In contrast, a progressive recovery of ACTH and cortisol responses after CRH was observed at different intervals of time in all patients but one. Five patients, in whom the cortisol concentration only normalized after surgery, showed a persistent responsiveness to desmopressin, and two of them relapsed 12 and 24 months later. In five patients who were not cured, the hormonal responsiveness to either CRH or desmopressin was similar before and after operation. Of 10 patients studied only after long-term follow-up, six were cured and a normal response to CRH was present, whereas no changes in ACTH/cortisol concentrations were induced by desmopressin. The other four unsuccessfully operated patients underwent pituitary irradiation and showed different and equivocal hormonal responses to desmopressin and to CRH. CONCLUSIONS: During the postoperative follow-up of patients with Cushing's disease, the maintenance or the disappearance of the hormonal response may be related to the persistence or the complete removal of adenomatous corticotrophs, respectively. It is suggested that desmopressin test should be performed in the preoperative evaluation and follow-up of patients with ACTH-dependent Cushing's syndrome.

Adolescent↗

PubMed2006

Plasma pharmacokinetics of desmopressin following sublingual administration: an exploratory dose-escalation study in healthy male volunteers.

OBJECTIVE: Desmopressin is usually administered intranasally in the treatment of central diabetes insipidus or nocturnal enuresis. The sublingual administration of desmopressin is expected to be an alternative to the intranasal route with advantages to children and to patients with allergic rhinitis or chronic rhinosinusitis. Therefore, the present study was carried out to explore the time-versus-concentration profile of desmopressin in plasma after sublingual administration to healthy volunteers. SUBJECTS AND METHODS: A total of 16 healthy male volunteers were enrolled in this open, exploratory, 1-period, randomized, dose-escalation study. Volunteers received a single sublingual dose of either 20, 40, 80, 160, 240 or 320 microg of desmopressin acetate. Desmopressin plasma concentrations were measured over a 12-hour period using a validated radioimmunoassay method. Safety and tolerability were assessed simultaneously. RESULTS: Plasma concentrations of desmopressin were below the lower limit of quantification (LLOQ) of 5 pg/ml for doses lower than 80 microg. For the doses of 160 - 320 microg the time-versus-concentration profiles were higher than the LLOQ. The area under the curve from 0 - 12 h (AUC0-12h) was 54.66 +/- 25.92 pg x h/ml after the 160 microg dose, 104.38 +/- 79.10 pg x h/ml following the 240 microg dose and 133.18 +/- 181.84 pg x h/ml following the 320 microg dose. Given the data from previous experiments, the time-versus-concentration profile of desmopressin in plasma after a sublingual dose of 240 microg appeared to be in the range of previously published data on an intranasal dose of 20 microg. Sublingual administration of desmopressin proved to be safe and was well tolerated by all volunteers. CONCLUSION: A very high inter-individual variability in desmopressin plasma concentrations was detected after sublingual administration. A sublingual dose of 240 microg of desmopressin appeared to result in a pharmacokinetic profile comparable to 20 microg administered intranasally. These data, however, need to be verified in a separate well-designed prospective clinical study.

Administration, Oral↗