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Clonidine may have a beneficial effect on refractory nocturnal enuresis. BACKGROUND: Although the evidence-based treatment for nocturnal enuresis is established, nearly one-third of patients are still enuretic with desmopressin, anti-cholinergic treatment and alarm. The fourth option, imipramine, is limited because of the risk of cardiotoxicity on overdose. Clonidine, an α2 -adrenoceptor agonist that also has noradrenergic effects like imipramine, is a new option for refractory enuresis. METHODS: A total of 148 patients (6-14 years of age; mean, 9.1 years) with refractory enuresis under desmopressin, anti-cholinergic treatment and alarm were enrolled. The patients consisted of 100 boys and 48 girls, of whom 23 had monosymptomatic nocturnal enuresis and 125 had non-monosymptomatic nocturnal enuresis. Clonidine 4 μg/kg/day (maximum, 75 μg/day) orally 30 min before bedtime was added and its effects were evaluated after 4 weeks of treatment. RESULTS: A total of 83 patients (56.1%) achieved partial or complete response with the additional clonidine. No significant adverse reactions were noted. CONCLUSIONS: Clonidine could be an aid for refractory enuresis, although further randomized controlled trials are needed.