DDAVP and Nocturnal Enuresis: Expensive and Not a Cure
ABSTRACT & COMMENTARY
Synopsis: According to the author, the explanation for nocturnal enuresis is multifactorial. Therefore, failure of any single treatment modality, such as the use of desmopressin, to successfully cure enuresis is not surprising.
Source: Koff SA. Cure of nocturnal enuresis: Why isn’t desmopressin very effective? Pediatr Nephrol 1996;10:667-670.
The use of desmopressin (ddavp) to treat nocturnal enuresis has had mixed success. Response rates, that is, improvement in number of dry nights, has been good (~70%), but cure rates have been disappointing (< 25%). The proposed rationale for the use of DDAVP is that some children with nocturnal enuresis have an absence of the circadian increase in vasopressin secretion that normally occurs at night. In the absence of the subsequent physiological decrease in urine production, DDAVP exerts its similar effect and should be successful in children with this defect. The disturbance in circadian vasopressin secretion occurs in only about 25% of enuretic children, and other explanations for nocturnal enuresis have been postulated. These include: 1) high rates of urine production as seen in diabetes mellitus or a renal concentrating defect as in sickle cell anemia; 2) alterations in vasopressin release independent of circadian rhythm; 3) urodynamic factors, including bladder capacity and/or instability associated with filling or position change; and 4) CNS responses, including altered sleep states and EEG responsiveness.
In his review, Koff, a pediatric urologist at Ohio State, proposes dual, coexisting mechanisms in the central nervous system (CNS) that normally mature by about 5 years of age to be largely responsible for many cases of childhood enuresis. The first, "afferent developmental delay," is characterized by failure of the CNS to recognize or respond to bladder distention or contractions, that is, a failure to arouse the child from sleep. In the second, "efferent developmental delay," the CNS does not recognize or suppress the micturition reflex, resulting in bladder contraction. The role of DDAVP effectiveness using this hypothesis is to decrease urine production and hence delay bladder filling and make uncontrolled bladder contractions less likely, thus explaining the partial success of a single therapeutic agent in a multifactorial problem.
COMMENT BY THOMAS KENNEDY, MD, FAAP
Enuresis remains a significant and bothersome problem for the child and his or her family, as well as a frustrating complaint for the pediatrician. Once we establish that a child over the age of 5 has primary nocturnal enuresis, we need not worry about serious physical or emotional etiology, but we would desperately like to provide effective therapy. Prevention of the secondary emotional trauma and stigma of this common problem through counseling and advice is helpful, and most any genuine interest, attention, and encouragement we can direct at the child and the family may yield substantial improvement. The use of behavior modification and alarm (pad and bell) systems have been helpful in some studies, although it is important to remember that there is a significant annual spontaneous resolution rate, so any intervention may appear to be effective. Still, there is no medication that provides impressive, safe, and long-term relief. Although imipramine is effective in the majority of children while it is used, it poses a danger in the household for toxic ingestion, and its chronic use may be associated with adverse effects. DDAVP, although reasonably safe, is only partially effective and extremely expensive.
Our frustration with nocturnal enuresis goes beyond our inability to effectively treat it. The etiology is likewise elusive and makes us uncomfortable in trying to explain to a family that the problem their child has, which is so disruptive to the household, is not only not serious and is not the child’s fault, but it is also unexplainable, untreatable, and destined to resolve at some unknown time in the future. Koff’s hypothesis brings some semblance of a rationale for the causes of nocturnal enuresis and the limitations for therapeutic interventions.
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