Reboxetine in therapy-resistant enuresis: A randomized placebo-controlled study.
INTRODUCTION
A significant minority of children with enuresis do not respond to either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use.


AIM
The aim was to determine whether there is a role for the noradrenergic antidepressant reboxetine, as monotherapy or combined with desmopressin, in the treatment of enuresis in children who have not responded to standard therapy, and whether there are side effects involved. We also sought prognostic factors in anamnestic data and in the voiding chart.


PATIENTS AND METHODS
The study was a randomized placebo-controlled study with a double-blind cross-over design, in which all patients underwent treatment during three 4-week periods, one with reboxetine 4 mg and placebo, one with reboxetine 4 mg and desmopressin, and one with double placebo treatment. The proportion of wet nights out of 14 was compared before treatment and during the last 2 weeks of each treatment period.


RESULTS
Eighteen patients were included. The reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p = 0.002) (Figure). However, only one patient achieved complete dryness, this during monotherapy. There were three intermediate responders to monotherapy and five to combination treatment. With reboxetine in monotherapy, six children experienced negative side effects compared with three with combination therapy, and two with placebo. All of these side effects were mild and reversible. Only one patient chose to cease treatment because of side effects. No prognostic factors were found in either the case history or in voiding chart data.


DISCUSSION
The present study, the first placebo-controlled trial, confirms that reboxetine is an evidence-based alternative to cardiotoxic antidepressant treatment in therapy-resistant enuresis. The fact that few patients achieved complete dryness may be due to the low dosage used. In our clinical practice we increase the dose to 8 mg when dryness is not achieved with the lower dose. Our experience is that this leaves more children with full response, but the evidence of this has yet to be shown.


CONCLUSION
Reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment.