Of enuresis

Five to seven million children and adolescents in the United States suffer from nocturnal enuresis. Primary enuresis is twice as common as secondary enuresis. Enuresis is twice as common in boys as compared to girls. The incidence of enuresis varies as a function of age24,25 ... 

The etiology of enuresis is poorly understood, but there is a clear genetic link. The incidence in children from families in whom there are no members with enuresis, where one parent had enuresis as a child, and where both parents had enuresis as children are 14%, 44%, and 77%, respectively. Loci for enuresis have been located on chromosomes 12,13, and 22. Sleep disorders are not considered major contributors with the exception of sleep apnea. Enuresis occurs in all sleep stages in proportion to the time spent in each stage. However, a small proportion of individuals are not aroused from sleep by bladder distention and have uninhibited bladder contractions preceding enuresis. 

TABLE 50-5. Major Potentially Treatable Organic Causes of Enuresis... 

The causes of enuresis and what things the patient and/or caregiver(s) can do to reduce its frequency... 

It should be noted that TCA dosages for the treatment of enuresis are often lower than those seen with the treatment of other disorders. It has been presumed that this level of dosing is efficacious because the TCAs are acting directly in the CNS, and the benefits seen not due to a peripheral anticholinergic side effect seen only at higher doses. 

The pharmacologic treatment of enuresis in children and adults with MR is a subject that has been more extensively studied than most other diagnoses. Enuresis causes significant anxiety for those experiencing it as well as for those who care for them. Approximately 20% of 5-year-old children wet the bed at least monthly, while by age 6 only 10% wet the bed. There is a 15% remission rate each year after age 6. 

A review of 18 controlled studies in otherwise typically developing children (Moffatt et ah, 1993) demonstrated that only about 24% of children were completely dry while on medication and that 94% relapsed after medication was discontinued. In the Swedish Enuresis Trial (SWEET), 399 children aged 6-12 years with primary enuresis participated in an open, multicenter trial of DDAVP (Tullus et ah, 1999). Subjects were observed for 4 weeks and had their DDAVP dose titrated over 6 weeks (20 0 pg), followed by a 1-year long-term treatment period. A total of 245 children (61%) experienced a 50% or more reduction in the number of wet nights, with resolution of enuresis in 77 children. The greatest therapeutic effect was observed in children 6-7 years of age. There were no studies on the effectiveness of DDAVP in children with MR. 

Administration of an AVP analog, such as desmopressin acetate (DDAVP), can produce a 30% to 60% reduction in wet nights in general, and about a 50% resolution of enuresis while on the medication (Norgaard et ah, 1985 Klauber, 1989 Norgaard et al.. 

Longstaffe, S., Moffatt, M.E. and Whalen, J.C. (2000) Behavioral and self-concept changes after six months of enuresis treatment a randomized, controlled trial. Pediatrics 105 935-940. 

Del Gado R, Del Gaizo D, Cennamo M, Auriemma R, Del Gado G, Verni M. Desmopressin is a safe drug for the treatment of enuresis. Scand J Urol Nephrol 2005 39 308-12. 

Ephedrine, given im/iv/sc, is indicated for the treatment of acute hypotensive states, treatment of Adams-Stokes syndrome with complete heart block, stimulation of the central nervous system (CNS) to combat narcolepsy and depressive states, treatment of acute bronchospasm, treatment of enuresis, and treatment of myasthenia gravis. When given in nasal form, ephedrine is used in the treatment of nasal congestion, promotion of nasal or sinus drainage, or relief of eustachian tube congestion. 

Preference of some prescribers for imipramine over other TCAs for the treatment of enuresis is based more upon art and anecdote and empiric clinical experience than comparative clinical trials with other TCAs... 

Tricyclic antidepressants are used to treat depression. They are also used for treatment of enuresis in children, chronic pain syndromes, neuropathic pain, the fibromyalgia syndrome, and chronic headaches. 

The essential feature of enuresis is repeated involuntary or intentional voiding of urine by day or night that is not caused by a general medical condition (Table 61-7). Medical causes of inappropriate voiding (e.g., diabetes mellitus, diabetes insipidus, seizure disorders, or urinary tract infections) should be ruled out. Enuresis may be primary or secondary. Primary enuresis, the most common type, is diagnosed if the child has never established urinary continence. Secondary enuresis follows an established period (3 to 6 months) of urinary continence. 

At age 5, prevalence is 15% to 20% at age 10 it is 5% for adolescents it is 1%, and 0.5% of adults wet the bed at least once a month. There is a 15% annual rate of spontaneous remission. The ratio of males to females with enuresis is 3 2. Factors that predispose a child to either type of enuresis include a positive family history. 

Although several antidepressants are EDA-approved for use in children, only one, fluoxetine, is currently approved for childhood depression. Imipramine is approved for the treatment of enuresis, clomipramine for obsessive-compulsive disorder in children 12 years and older, and fluvoxamine along with fluoxetine is approved for obsessive-compulsive disorder in children. The treatment of depression in children remains challenging, as depression can be difficult to diagnose and treat once identified. The studies involving imipramine, sertraline, and fluoxetine found that the dose range and titration as well as adverse effects were similar to those in adults. " ... 

OTHER THERAPEUTIC USES OE THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologicaUy to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nortriptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy. 

An 11-year-old boy with ADHD was given methylphenidate and after the daily dosage had been titrated to 20 mg enuresis started to occur. After 2 months, the medication was withdrawn and the enuresis stopped immediately. About 1 month later, methylphenidate was restarted and the enuresis reoccurred when the dose reached 20 mg/day. It continued for about 3 months but immediately stopped when the medication was withdrawn. Another rechallenge after 2 months, followed by withdrawal of methylphenidate, replicated the response. Other causes of enuresis were excluded and the patient never had daytime urinary incontinence. 

The causes of enuresis are always functional the causes of incontinence may be organic or functional, but are mostly functional (Kelleher 1997). Functional causes can be divided as mentioned above in this chapter into overactive bladder (unstable bladder) and dysfunctional voiding in particular. 

Any attempt to make the important distinction between monosymptomatic nocturnal enuresis and incontinence based on the patient s history and clinical symptoms alone may fail and occult underlying functional disorders of the lower urinary tract may be overlooked. This may contribute to the different rates of success for a heterogeneous spectrum of therapeutic measures in different studies and may contribute to different statements regarding prognosis and associated disorders of enuresis. 

Lee SD, Sohn DW, Lee JZ et al (2000) An epidemiological study of enuresis in Korean children. BJU Int 85 869-873 Leung VY, Metreweli C, Yeung CK (2002a) Immature ureteric jet Doppler patterns and urinary tract infection and vesicoureteric reflux in children. Ultrasound Med Biol 28 873-878... 

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