Nocturnal enuresis: a placebo controlled trial of two antidepressant drugs.

Abstract

A multicentre, randomised, double blind treatment trial was set up comparing imipramine (a tricyclic antidepressant with anticholinergic action), mianserin (a quadricyclic antidepressant without anticholinergic activity), and placebo, (a) possibly to identify an effective alternative drug and (b) to elucidate the action of imipramine in enuretic children. Eighty children (65 boys, 15 girls) aged 5-13 years, wet three or more nights a week, were studied. Exclusions were a urinary tract infection or abnormality, other organic illness, or severe emotional disorders. After a four week assessment, 25 children were randomised to eight weeks' treatment with imipramine 25 mg, 26 to mianserin 10 mg and 29 to placebo, followed by four weeks without treatment. Dry nights and a wetness score were recorded throughout.During treatment, imipramine was superior to both placebo and mianserin (p < 0.001) in achieving dry nights and reducing wetness scores. It led to a definite improvement in 72% of children. Mianserin produced a mildly beneficial effect that was not superior to placebo. No side effects were recorded.Mianserin would not be a satisfactory alternative treatment for nocturnal enuresis. The efficacy of imipramine is unlikely to be the result of its antidepressant activity. (Arch Dis Child 1996;75:62-66) Keywords: nocturnal enuresis, mianserin, imipramine. Imipramine has been used effectively,"4 although it may cause side effects when the dosage is increased and a relapse may follow cessation of treatment. It also carries a risk of accidental poisoning if swallowed by younger siblings, 5 although this is now infrequent. The mechanism of action of imipramine is uncertain and has been attributed variously to a central antidepressant effect, or anticholinergic action, or to a direct effect on the bladder trigone. 4 In view of the need for a safe and effective alternative to imipramine, an international multicentre, randomised, double blind therapeutic trial was set up involving centres in Finland, the Netherlands and Britain, comparing the effects of the tricyclic antidepressant imipramine, a quadricyclic antidepressant mianserin, and placebo. The dual objective was to search for a possible alternative drug treatment with a sustained response and to explore the mechanism of action of imipramine by comparing two effective antidepressant drugs, only one of which, imipramine, has additional anticholinergic activity. The results are presented in 80 children studied in the British centres: Southampton, Leeds, and Aberdeen. Southampton and MethodsThe protocol of the study is outlined in fig 1 and was approved by each ethical committee. RECRUITMENTChildren aged 5-13 years with nocturnal enuresis, bed wetting at least three nights a week, were recruited. (One child was included who had an earlier very wet record but who had an average of only 2.5 wet nights a week in the preceding four weeks.) The history was taken, a full clinical examination including height, weight, and blood pressure was carried out and a Rutter A ...

Placebo-Controlled Study of the Effects of Atomoxetine on Bladder Control in Children With Nocturnal Enuresis

“…Another theory is that the anticholinergic effect of the drug might decrease bladder contractility, leading to increased bladder filling and improved functional bladder capacity (Thiedke 2003). But it also has been suggested that the therapeutic benefit of imipramine is not due to the antidepressant or anticholinergic actions, but rather a direct noradrenergic effect on the bladder or a central effect other than antidepression (Smellie et al 1996). Early studies demonstrated that depression of the vesicosympathetic pathway to the urinary bladder could be produced by L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of norepinephrine, by paramethoxyphenylethylamine, an agent thought to release norepinephrine from nerve terminals (De Groat and Lalley 1972) and by clonidine, an adrenergic ␣ 2 agonist (De Groat and Douglas 1975).…”

“…The generally accepted prevalence of nocturnal enuresis is 15% at 5 years of age, with a spontaneous resolution rate of approximately 15% per year (Smellie et al 1996;Cendron 1999). Although a number of studies report that nocturnal enuresis is more common in boys than girls, this finding is disputed in other reports.…”

Tolterodine and imipramine in refractory enuresis; a placebo-controlled crossover study

“…The old tricyclic antidepressant imipramine has in numerous studies proven to be superior to placebo in the treatment of unselected children with nocturnal enuresis [12][13][14][15]. For several decades, it was more or less the drug of choice and was widely prescribed all over the world.…”

The Evaluation and Treatment of Therapy-Resistant Enuresis: A Review

“…The tricyclic antidepressant imipramine has in several placebo-controlled studies shown better effect than placebo against nocturnal enuresis (18)(19)(20). This drug was widely used for this indication during the 60s and 70s and is still so in some parts of the world, but its use has been steeply diminishing since the alarm and desmopressin became established.…”