Enuresis with

Tullus, K., Bergstron, R., Fosdal, I., Winnergard, I., and Hjalmas, K. (1999) Efficacy and safety during long-term treatment of primary monosymptomatic nocturnal enuresis with desmopressin. Acta Paediatr. 88 1274-1278. 

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. 

Non-REM parasomnias have variable prevalence rates depending on patient age and different diagnoses. Sleep talking, brux-ism, sleepwalking, sleep terrors, and enuresis occur more frequently in childhood than in adulthood. Nightmares appear to occur with similar frequency in adults and children. REM behavior disorder (RBD), an REM-sleep parasomnia, has a reported prevalence of 0.5% and frequently is associated with concomitant neurologic conditions.16 Chronic RBD is more common in elderly men and may have a familial disposition. 

List the treatment goals for a patient with urinary incontinence or pediatric enuresis. 

Urinary frequency (greater than 8 micturitions/day), urgency with or without urge incontinence nocturia (greater than or equal to 2 micturitions/night) and enuresis may be present as well. 

Five to ten percent of children with enuresis will suffer the condition as adults. It may also predispose to UUI in adults. In the enuretic population, 80% to 85% are monosymptomatic, 5% to 10% are polysymptomatic, and under 5% have an organic cause. The spontaneous annual cure rate (i.e., restoration of continence) ranges from 14% to 16% (exception at about 4 or 5 years of age, it may be as high as 30%). 

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. 

The vast majority of children with enuresis have normal uro-dynamics, including nocturnal bladder capacity. Functional bladder capacity can be estimated using this formula age in years + 2 = ounces of capacity. In some children, there appears to be a relationship between developmental immaturity (motor and language milestones) and enuresis, but the mechanism is unknown. Drugs like lithium, clozapine, risperidone,... 

Proper assessment of the child or adolescent with enuresis should explore every aspect of urinary incontinence, especially the genitourinary and nervous systems. The minimum assessment should include24 25 ... 

The two primary agents used to treat enuresis are desmopressin and imipramine (Table 50-7). Desmopressin is the drug of choice in pediatric enuresis. Anticholinergics have a limited role (Table 50-7). Other agents have been studied with inconclusive results.28... 

Fritz G, Rockney R, Bernet W, et al. Practice parameter for the assessment and treatment of children and adolescents with enuresis. J Am Acad Child Adolesc Psychiatry 2004 43 1540-1550. 

Amphetamine (Benzedrine). Amphetamine was synthesized in 1887. It was quickly found to be a potent stimulant with effects similar to cocaine, which had been discovered over 100 years before. In the subsequent years, amphetamine found a variety of uses. It was used to treat narcolepsy, Parkinson s disease, barbiturate overdose, bed wetting (enuresis), and obesity. It was also used to counteract the sedating effects of other drugs and medications including antiseizure medications and alcohol. 

Because it is stable, desmopressin is preferred for treatments especially if pressor effects are not desired. The primary indication for therapy is central diabetes insipidus, a disorder that results when ADH secretion is reduced and that is characterized by polydipsia, polyuria, and dehydration. Desmopressin is also used to reduce primary nocturnal enuresis, or bedwetting, in children. It is useful in people with mild hemophilia A or with some types of von Willebrand s disease, in which von Willebrand s factor is present at low levels. In these cases, desmopressin is given when excessive bleeding occurs or before surgery to help reduce bleeding indirectly by increasing the amounts of coagulation factors. 

Unlabeled Uses Relief of neuropathic pain, such as that experienced by patients with diabetic neuropathy or postherpetic neuralgia treatment of anxiety, bulimia nervosa, migraine, nocturnal enuresis, panic disorder, peptic ulcer, phantom limb pain... 

Mechanism of Action Atricyclicantidepressant, antineuralgic, andantineuriticagent that blocks the reuptake of neurotransmitters, such as norepinephrine and serotonin, at presynaptic membranes, increasing their concentration at postsynaptic receptor sites. Therapeutic Effect Relieves depression and controls nocturnal enuresis. Pharmacokinetics Rapidly, well absorbed following PO administration. Protein binding more than 90%. Metabolized in liver, with first-pass effect. Excreted in urine as metabolites. Half-life 6-18 hr. 

Approximately three-quarters of children with OCD have comorbid diagnoses. These include tic disorders (24%-30%) and mood disorders, especially major depression (26%-29%). Riddle and colleagues (1990) found that 38% of children with OCD have other anxiety disorders, while Swedo (1989) more specifically identified increased rates of simple phobias (17%), overanxious disorder (16%), and separation anxiety disorder (7%). Other reported comorbidities include specific developmental disabilities, adjustment disorder with depressed mood, oppositional defiant disorder, attention-deficit hyperactivity disorder (ADHD), conduct disorder, and enuresis/encopresis (Swedo et ah, 1989b Riddle et ah, 1990). 

Multiple studies have been done of TCAs in the treatment of nocturnal enuresis, and all consistently show effect over placebo. Most notably, Rapoport et al. (1978) found a significant relationship between IMI plasma level and response to medication. Imipramine is the only medication with FDA approval for treatment of this condition. 

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. 

A fourth and final part. Other Areas of Clinical Concern, addresses the pharmacological management of aggressive or agitated children, and those with the elimination disorders enuresis or encopresis. 

Tricyclic antidepressants have been used for decades to treat depression and anxiety in the general population, and clomipramine has been used to treat OCD. Clomipramine has been studied with respect to treating school phobia or school refusal (Berney et ah, 1981). Gittleman-Klein and Klein (1971) found imipramine to be superior to placebo in treating school refusal. As the TCAs may improve other disorders such as nocturnal enuresis, ADHD, and sleep disorders, they may be attractive for children with any of these comorbid conditions and anxiety disorder. 

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. 

Behavioral therapies are the treatment of choice for enuresis in both typically developing children and children with MR. No medical intervention should be undertaken before considering behavioral interventions, such as a star chart for dry nights, evening fluid restriction, bladder-stretching exercises (where children are asked to hold their urine for as long as they can, past the initial bladder spasm), and/or the buzzer-and-pad. However, some MR/DD patients will be unable to cooperate with such strategies and may need medical... 

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. 

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