Nocturnal 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 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,... 

In the absence of an identified cause and comorbidities, monosymptomatic nocturnal enuresis is present which can be amenable to nonpharmacologic and pharmacologic therapies. Nonpharmacologic therapy should be utilized initially, provided that the patient and family are sufficiently motivated. Use of one nonpharmacologic method at a time is reasonable, provided that each is given an adequate trial period. If response is suboptimal after 6 months, a different method should be substituted or added. There is some evidence to... 

Oxybutynin has no significant effect in monosymptomatic nocturnal enuresis. Oxybutynin and related agents (see adult UI section of this chapter) should be used only if the patient has concurrent daytime urgency or frequency. 

Hjalmas K, Arnold T, Bower W, et al. Nocturnal enuresis an international evidence based management strategy. ] Urol 2004 171(6 Pt 2) 2545-2561. 

Desmopressin is used for the therapy of diabetes insipidus (ADH deficiency), nocturnal enuresis, thrombasthe-mia (p. 148), and chronic hypotension (p. 314) it is given by injection or via the nasal mucosa (as snuff ). 

Children Not recommended for patients younger than 12 years of age. Safety and efficacy are not established for amoxapine in children younger than 16 years of age or trazodone or clomipramine in children younger than 10 years of age. The safety and efficacy of imipramine as temporary adjunctive therapy for nocturnal enuresis in pediatric patients younger than 6 years of age have not been established. The safety of the drug for long-term, chronic use as adjunctive therapy for nocturnal enuresis in pediatric patients 6 years of age and older has not been established. Safety and efficacy are not established in the pediatric age group for trimipramine, nortriptyline, protriptyline, and desipramine. 

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. 

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. 

St. John s wort has been used to treat a wide range of ailments for more than 2000 years, and is said to have been prescribed by Hippocrates himself. Apart from depression, St. John s wort is being promoted or used as a treatment for attention-deficit hyperactivity disorder (ADHD), anxiety, stress, obsessive-compulsive disorder, sleep problems, nocturnal enuresis, bacterial and viral infections such as HIV-AIDS, respiratory conditions, peptic ulceration, inflammatory arthritis, cancer, and skin wounds (Rey and Walter, 1998 Walter et ah, 2000). It is also said to increase libido, an application dating from the Middle Ages (Fletcher, 1996). No empirical evidence is currently available to support any of these uses. 

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. 

Blackwell, B. and Currah, J. (1973) The psychopharmacology of nocturnal enuresis. In Kolvin, L, McKeith, R., and Meadow, S., eds. Bladder Control and Enuresis. London Hineman, pp. 231-257. 

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. 

FIGURE 51.3 Paradigm for pure nocturnal enuresis intervention. TCAs, tricyclic antidepressants. 

Behrle, R.C. (1956) Evaluation of a conditioning device in the treatment of nocturnal enuresis. Pediatrics 17 849. 

Glazener, C.M. and Evans, J.H. (2000) Desmopressin for nocturnal enuresis in children. Cochrane Database Syst Rev 2 ... 

Hogg, R.J. and Husmann, D. (1993) The role of family history in predicting response to desmopressin in nocturnal enuresis. / Urol 150 444-445. 

Hours, A.C. (1991) Nocturnal enuresis as a biobehavioral problem. Behav Ther 22 133-151. 

Klackenberg, G. (1981) Nocturnal enuresis in a longitudinal perspective. A primary problem of maturity and/or a secondary environmental reaction Acta Paediatr Scand 70 453-457. 

Klauber, G.T. (1989) Clinical efficacy and safety of desmopressin in the treatment of nocturnal enuresis. / Pediatr 114 719-722. 

Norgaard, J.P., Rittig, S., and Djurhuus, J.C. (1989) Nocturnal enuresis an approach to treatment based on pathogenesis./ Pediatr 114 705-710. 

Ornitz, E.M., Russell, A.T., Gabikian, R, Gehricke, J.G., and Guthrie, D. (2000) Prepulse inhibition of startle, intelligence and familial primary nocturnal enuresis. Acta Paediatr 89 475-481. 

G. (1999) Molecular genetics of nocturnal enuresis linkage to a locus on chromosome 22. Scand J Urol Nephrol Suppl 202 76-... 

In 1995, Bramble published a study on the prescription frequency of antidepressants by British child psychiatrists (Bramble, 1995). A brief postal questionnaire was circulated to 350 members of the British Royal College of Psychiatrists, Child and Adolescent Psychiatry Specialist Sections. There was a 71% response rate, and 85% of the 238 respondents had employed antidepressants, the most popular of these being amitriptyline and imipramine. Nearly one-third of the psychiatrists at that time used neuroagents occasionally, and the SSRIs were used only very rarely. The antidepressant medication was used for a wide range of child and adolescent disorders beyond those of depression and nocturnal enuresis. Approximately 20% of the prescriptions were given for ADHD (hyperkinetic disorder), conduct disorder, and a few cases of autistic disorder. Clomipramine was apparently given for OCD. On the basis of these 1994 data. Bramble concluded that British child psychiatrists tend to use antidepressant medication far less often than American psychiatrists. 

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