Effect of desmopressin on water and solute circadian rhythms in treatment-naïve children with monosymptomatic enuresis and nocturnal polyuria.

Background: Enuresis has a complex pathophysiology involving nocturnal polyuria, reduced bladder capacity at nighttime, and impaired arousability. Desmopressin has long been used as a treatment. However, approximately 30% of children do not fully respond to it, suggesting the involvement of other factors.

First uninterrupted sleep period in children and adolescents with nocturnal enuresis: Added value in diagnosis and follow-up during therapy.

Background: The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies.

Aim: Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis.

Desmopressin oral lyophilisate in young children: new insights in pharmacokinetics and pharmacodynamics.

Objective: To study the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of desmopressin (dDAVP) oral lyophilisate in children below the age of 8 years with special emphasis on age-related and size-related differences in bioavailability.

Design: Open label, non-randomised, interventional PK and PD trial.

Setting: Single-centre study.

An Integrated Paediatric Population PK/PD Analysis of dDAVP: How do PK Differences Translate to Clinical Outcomes?

Introduction: The bioequivalence of two formulations of desmopressin (dDAVP), a vasopressin analogue prescribed for nocturnal enuresis treatment in children, has been previously confirmed in adults but not in children. In this study, we aimed to study the pharmacokinetics (PK) and pharmacodynamics (PD) of these two formulations, in both fasted and fed children, including patients younger than 6 years of age.

Methods: Previously published data from one PK study and one PK/PD study in children aged between 6 and 16 years were combined with a new PK/PD study in children aged between 6 months and 8 years, and analysed using population PK/PD modelling.

Claiming desmopressin therapeutic equivalence in children requires pediatric data: a population PKPD analysis.

Purpose: For a new formulation of a drug, only pharmacokinetic bioequivalence with the original formulation has to be demonstrated in healthy, young adults. However, "children are not small adults," and to guarantee a safe and effective treatment, age-adapted drug development is required. Desmopressin, a vasopressin analogue prescribed for nocturnal enuresis in children, was studied as an example formulation first developed in adults and then extrapolated to a pediatric indication.

Recent advances in managing and understanding enuresis.

Enuresis, particularly in children during sleep, can be a debilitating condition, affecting the quality of life of the child and his or her family. The pathophysiology of nocturnal enuresis, though not clear, revolves around the inter-related mechanisms of overactive bladder, excessive nocturnal urine production, and sleep fragmentation. The first mechanism is more related to isolated nocturnal voiding, whereas the latter two are more related to nocturnal enuresis, in which circadian variations in arginine vasopressin hormone play a key role.

Optimizing response to desmopressin in patients with monosymptomatic nocturnal enuresis.

Most patients with monosymptomatic nocturnal enuresis can be effectively treated with an enuresis alarm or antidiuretic therapy (desmopressin), depending on the pathophysiology of the condition in the individual patient. Desmopressin is first-line therapy for enuresis caused by nocturnal polyuria, an excessive urine output during the night. However, in a recent study, around one-third of patients thought to be resistant to desmopressin were subsequently treated effectively with desmopressin monotherapy in a specialist centre.

Desmopressin (melt) therapy in children with monosymptomatic nocturnal enuresis and nocturnal polyuria results in improved neuropsychological functioning and sleep.

Background: There is a high comorbidity between nocturnal enuresis, sleep disorders and psychological problems. The aim of this study was to investigate whether a decrease in nocturnal diuresis volume not only improves enuresis but also ameliorates disrupted sleep and (neuro)psychological dysfunction, the major comorbidities of this disorder.

Methods: In this open-label, prospective phase IV study, 30 children with monosymptomatic nocturnal enuresis (MNE) underwent standardized video-polysomnographic testing and multi-informant (neuro)psychological testing at baseline and 6 months after the start of desmopressin treatment in the University Hospital Ghent, Belgium.

Incontinence and psychological problems in children: a common central nervous pathway?

Nocturnal enuresis is caused by a mismatch between the nocturnal bladder capacity and the nocturnal diuresis rate, in the presence of a deficient arousability in the majority of patients, according to the pediatric and urologic literature. Psychiatric and psychologic literature are still concentrating on the potential role of psychological factors and central nervous mechanisms in the pathogenesis, as is reflected in the DMS-5 criteria. However, research has clearly shown several important comorbidities between neuropsychological dysfunctions and nocturnal enuresis.

Challenging factors for enuresis treatment: Psychological problems and non-adherence.

The evidence for organic pathogenetic factors in enuresis and the discovery of effective therapies targeting the bladder and/or nocturnal diuresis have overwhelmed every potential role of psychological factors in pathogenesis and treatment. However, psychopathology is still important in enuresis because according to the document of the International Children's Continence Society (ICCS) 20-30% of the children with enuresis have at least one psychological/psychiatric disorder at rates two times higher than non-wetting children. The most common comorbid disorder with enuresis is attention deficit hyperactivity disorder.

Predictive parameters of response to desmopressin in primary nocturnal enuresis.

Introduction/background: Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart.

Objective: The aim of this study was to identify any possible predictive factors to desmopressin response.

Sleep fragmentation and periodic limb movements in children with monosymptomatic nocturnal enuresis and polyuria.

Background: Children with nocturnal enuresis (NE) have been found to have sleep fragmentation and a high incidence of periodic limb movements in sleep (PLMS). This study explored the association of monosymptomatic NE and polyuria in relation to fluid intake, bladder volume, number of wet nights, and number of nights with polyuria to the frequency of PLMS and cortical arousals during sleep.

Materials And Methods: Thirty children with monosymptomatic NE and polyuria were enrolled in the study.

Periodic limb movements during sleep are associated with a lower quality of life in children with monosymptomatic nocturnal enuresis.

Unlabelled: The study investigates whether cortical arousals and periodic limb movements during sleep are related to daytime psychological functioning in children with monosymptomatic nocturnal enuresis with associated nocturnal polyuria. Psychological functioning is evaluated on five domains: attention deficit hyperactivity disorder-inattentive problems, quality of life, internalizing problems, externalizing problems, and executive functioning. This multi-informant (parents, teachers, and children) and multi-method study included overnight video-polysomnography, questionnaires, and neuropsychological testing.

Safety profile of desmopressin tablet for enuresis in a prospective study.

Introduction: This pre-specified sub-study of the desmopressin response in primary nocturnal enuresis study (DRIP study) evaluates the safety profile of the oral desmopressin tablet in children with primary nocturnal enuresis. Endpoints are adverse events and change in body mass index.

Methods: The DRIP study was an open-label, intention-to-treat, phase IV, multi-national study.

Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis.

Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration.

Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis.

Unlabelled: Primary nocturnal enuresis is a prevalent childhood condition that can persist into adulthood. Desmopressin is an antidiuretic available as orally disintegrating lyophilisate (melt) or solid tablet. Recent findings suggesting different food interactions and clinical characteristics, including compliance, between desmopressin melt and tablet motivated a post hoc analysis of a previously reported randomised, crossover study.

Is there still a role for desmopressin in children with primary monosymptomatic nocturnal enuresis?: a focus on safety issues.

It has recently became apparent that severe primary monosymptomatic nocturnal enuresis (MNE) has a worse prognosis than generally believed, and may have major consequences on the well-being of the child, thus making treatment mandatory. Desmopressin is one of the most widely prescribed medications for MNE, and in this current opinion article we discuss the safety of desmopressin in children with this condition. Following a US FDA request in December 2007 that the prescribing information for desmopressin nasal spray be updated, desmopressin spray is no longer indicated for the treatment of MNE or for use in patients at risk for hyponatraemia.

Poor compliance with primary nocturnal enuresis therapy may contribute to insufficient desmopressin response.

Purpose: Studies of desmopressin in children with primary nocturnal enuresis show a greater than 90% decrease in wet nights in 20% to 30%, a 50% to less than 90% decrease in 20% to 40% and less than a 50% decrease in up to 60%. Insufficient response to desmopressin is attributable to various factors, including differences in the primary nocturnal enuresis definition, underlying bladder dysfunction and/or desmopressin pharmacokinetic characteristics. However, little attention has been given to poor compliance with therapy as a possible explanatory factor.

Abnormal sleep architecture and refractory nocturnal enuresis.

Purpose: The relation between sleep and nocturnal enuresis has been an area of discussion for many years. Children with enuresis are generally believed to have sleep that is too deep with decreased arousability. We investigated sleep characteristics in children with refractory nocturnal enuresis.