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Nocturnal polyuria, nocturnal detrusor overactivity and high arousal thresholds are central in the pathogenesis of enuresis. An underlying mechanism on the brainstem level is probably common to these mechanisms. Enuretic children have an increased risk for psychosocial comorbidity. The primary evaluation of the enuretic child is usually straightforward, with no radiology or invasive procedures required, and can be carried out by any adequately educated nurse or physician. The first-line treatment, once the few cases with underlying disorders, such as diabetes, kidney disease or urogenital malformations, have been ruled out, is the enuresis alarm, which has a definite curative potential but requires much work and motivation. For families not able to comply with the alarm, desmopressin should be the treatment of choice. In therapy-resistant cases, occult constipation needs to be ruled out, and then anticholinergic treatment-often combined with desmopressin-can be tried. In situations when all other treatments have failed, imipramine treatment is warranted, provided the cardiac risks are taken into account.

The anticholinergic drug tolterodine has been suggested to be useful in therapy-resistant enuresis. Imipramine has a proven efficiency in unselected enuretic patients, but due to its side-effect profile it is only indicated, if at all, in therapy-resistant cases. We therefore compared these two drugs to placebo. Twenty-seven children with enuresis resistant to the alarm and to desmopressin in monotherapy were given placebo, tolterodine 1-2 mg, and imipramine 25-50 mg at bedtime for 5 weeks each in a randomised, double-blind, crossover fashion. The number of wet nights during the last 2 weeks of each treatment period was compared. One patient became spontaneously dry at the start of the study, and one dropped out due to side effects. Among the remaining 25 children, the number of wet nights during placebo, tolterodine and imipramine treatment were 11.0 +/- 3.9, 10.4 +/- 3.9 and 7.8 +/- 5.1, respectively (p < 0.001). Imipramine was significantly better than both placebo (p = 0.001) and tolterodine (p = 0.006). Nine children experienced side effects on imipramine and one on tolterodine (p = 0.001). This is the first study on anticholinergics or imipramine in children with therapy-resistant enuresis. Tolterodine, in monotherapy, had no proven effect. Imipramine was better than placebo, but side effects were common.