Enuresis in Children: Combination Therapy Effective

Lara C. Pullen, PhD

February 10, 2012

February 10, 2012 — Combination therapy with desmopressin and the anticholinergic agent oxybutynin is effective in the treatment of monosymptomatic nocturnal enuresis (MNE; 45% success compared with 17% success in placebo group: odds ratio [OR], 0.24; 95% confidence interval [CI], 0.10 - 0.56; P < .01).

The randomized, double-blinded, placebo-controlled trial, performed by Paolo Montaldo, MD, from the Second University of Naples in Italy, and colleagues, was published online February 7 in the British Journal of Urology International. The authors found that the combined therapy was especially effective for children with enuresis who have a restricted bladder capacity and thickened bladder wall.

The study included 206 patients between the ages of 6 and 13 years (mean age, 10.6 ± 2.9 years) who had MNE with a median of 6.6 wet nights per week. Patients were randomly assigned to receive either 120 μg desmopressin or 240 μg desmopressin for 2 weeks. The 120-μg and the 240-μg desmopressin initial dose both gave the same degree of response (OR, 1.44; 95% CI, 0.83 - 2.48; P = .19).

Patients who experienced treatment failure with desmopressin alone were randomly assigned to receive desmopressin plus 5 mg oxybutynin or desmopressin plus placebo for 4 weeks.

Ultrasonography-measured bladder variables were predictive for a diagnosis of MNE, as well as predictive of response to combination therapy or treatment with desmopressin alone. The results were consistent with previous studies indicating that a normal bladder volume and wall thickness index of from 70 to 130 is highly predictive of a good response to desmopressin.

Full responders to combination therapy demonstrated both detrusor overactivity and nocturnal polyuria, whereas desmopressin full responders had greater nocturnal urine production than the partial and nonresponders (P < .01). Thirty-three patients did not respond to either treatment strategy, and they demonstrated neither detrusor overactivity nor polyuria as their predominant pathogenic factor.

Desmopressin is an analog to the antidiuretic vasopressin and is used as an evidence-based therapy for enuresis. Previous studies have had conflicting results as to whether a lower or higher initial dose of desmopressin is more effective.

The current study included patients who failed to respond to 120-μg desmopressin therapy, but responded to 240 μg desmopressin. This is consistent with pharmacodynamic data indicating a clear dose–response relationship for the duration of urinary-concentrating action. The dose of 120 μg would likely last through the early hours of the morning, when enuretic episodes are most likely to occur in children.

The authors write, "We suggest starting with the dose of 120 μg desmopressin and then, if the patient is therapy resistant or only a partial responder, the dose can be doubled, but only if the reappearance of diluting capacity and increased dieresis in the morning is documented."

The authors have disclosed no relevant financial relationships.

BJUI. Published online February 7, 2012. Abstract

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