Desmopressin Acetate and Nocturnal Enuresis: How Much Do We Know?

Objectives. Desmopress in acetate (DDAVP) is promoted to treat nocturnal enuresis but indications for its use are unclear. We reviewed all randomized controlled trials to determine (1) short- and long-term efficacy, (2) responders, (3) dose-response curve, (4) side effects, and (5) comparative efficacy with other treatments. Methods. A Medline search of the English language literature from January 1966 to August 1992, supplemented by contact with the drug companies, yielded 18 articles which were true randomized controlled trials (11 cross-over and 7 parallel studies). Results. The 18 randomized controlled trials included 689 subjects for most of whom some other type of treatment had failed. All studies found decreased mean frequency of wetting ranging from 10% to 91%, but only 24.5% of subjects achieved short-term dryness. One study of DDAVP responders directly tested long-term dryness and 21% stayed dry. In three studies that incidentally reported on long-term effects 5.7% stayed dry after stopping DDAVP. There was wide variation in the type of patient included. Seven studies addressed prognostic factors. Children more than 9 years old and with fewer initial wet nights do better. Four studies seem to include almost exclusively monosymptomatic children with nocturnal enuresis (ie, primary nocturnal enuresis, positive family history, and no urinary symptoms). Results were no better than those which included mixed symptoms. Five studies attempted to address the dose-response issue. Despite some methodological issues, there is probably some dose-response effect. Side effects were infrequent in the 589 subjects who received DDAVP as opposed to placebo. No cases of water intoxication and no significant shifts in electrolytes were reported in the four studies which measured them. Nasal stuffiness, headache, epistaxis, and mild abdominal pain seem to be the only side effects noted, and these were uncommon. Only one study compared DDAVP with conditioning alarms. Alarm patients had 10% fewer wet nights and a better long-term result. Conclusions. DDAVP reduces wet nights in children for whom other treatments have failed but it produces complete dryness in a minority, and this is often a temporary effect. The literature focuses on short-term efficacy. The true role of DDAVP will be known when samples are carefully selected, prognostic factors are examined, and more comparisons with other treatments are conducted focusing on long-term outcomes. On the basis of current knowledge, DDAVP is inferior to conditioning alarms as a primary therapy.