A controlled study of imipramine (Tofranil) in the treatment of childhood enuresis

Poussaint, Alvin F.; Ditman, Keith S.

doi:10.1016/s0022-3476(65)80252-9

Cited by 105 publications

(13 citation statements)

References 21 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Nevéus

Tullus

2007

Pediatr Nephrol

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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.

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Section: Introductionmentioning

confidence: 99%

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

Nevéus

Tullus

2007

Pediatr Nephrol

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“…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.…”

Section: Imipraminementioning

confidence: 99%

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

Nevéus

2006

Upsala Journal of Medical Sciences

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Children with enuresis that neither responds to the alarm or to desmopressin medication usually have nocturnal detrusor over-activity combined with high arousal thresholds as a cause for their bedwetting.The evaluation of these children is focused on 1) excluding underlying pathology such as kidney disease, urinary tract infection or neurogenic bladder, 2) looking for concomitant day-time bladder problems or constipation, and 3) detecting possible reasons for failure of alarm treatment. A bladder diary is essential, but blood tests, radiological examinations or invasive procedures are seldom informative.The non-pharmacologic treatment of these children consists of eradication of constipation, if present, and the provision of advice regarding sound drinking and toilet habits. Such treatment is essential but not uniformly sufficient by itself.The first-line pharmacologic treatment of therapy-resistant enuresis is anticholinergic medication, although this is, as yet, not evidence-based. Anticholinergics can be combined with desmopressin for better efficiency. For children failing all these measures there is still a place for tricyclic antidepressant therapy, provided that adequate safety precautions are strictly observed. BACKGROUND

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“…Besides demonstrating a drug effect, several studies also found that enuresis frequency is influenced by many factors, with generally pronounced interindividual differences in the relative contribution of such factors to the problem. A clear placebo effect, usually occurring during the first week of treatment, has been observed in several studies (Kardash et aI., 1968;Poussaint and Ditman, 1965). Both hospitalisation and cold weather have been shown to influence the enuresis frequency (Drew, 1966).…”

mentioning

confidence: 89%

“…Drew. 1966;Kardash et ai., 1968;Maxwell and Seldrup, 1971;Poussaint and Ditman, 1965). Besides demonstrating a drug effect, several studies also found that enuresis frequency is influenced by many factors, with generally pronounced interindividual differences in the relative contribution of such factors to the problem.…”

mentioning

confidence: 99%

“…such milieu factors have not fully explained the interindividual variations in response to imipramine. The demonstration of a beneficial effect of increased imipramine doses in poor responders (Poussaint and Ditman, 1965) indicates that individual differences in drug kinetics may be of importance. The administration of standardised doses of imipramine to adults results in marked interindividual variations in the steady-state plasma concentration of imipramine and the formed metabolite desipramine (Gram et aI., 1977).…”

mentioning

confidence: 99%

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Plasma Concentration and Clinical Effect in Imipramine Treatment of Childhood Enuresis

Jørgensen

Lober

Christiansen

et al. 1980

Clinical Pharmacokinetics

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The relationship between steady-state plasma concentraton and clinical effect of imipramine in the treatment of nocturnal enuresis was studied in 22 hospitalised children. After 1 week on placebo the children were given imipramine in a fixed dose of about 1 mg/kg for 3 weeks. The enuresis frequency decreased significantly from the placebo to the first week on imipramine, but then no further improvement was observed. There was a significant correlation between steady-state plasma concentration of desipramine or imipramine + desipramine and the reduction in enuresis frequency during imipramine treatment. The optimum effect was obtained when steady-state levels of imipramine + desipramine were above 60 microgram/L; i.e. the effective concentration in enuresis is 3 to 4 times lower than in antidepressive therapy. Dose- and weight-corrected, steady-state plasma concentration of imipramine and desipramine were not significantly different from those previously observed in younger adults. In 1 child, a transient rise in imipramine and desipramine concentration was seen during a period with fever and bacterial infection.

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A controlled study of imipramine (Tofranil) in the treatment of childhood enuresis

Cited by 105 publications

References 21 publications

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

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

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

Plasma Concentration and Clinical Effect in Imipramine Treatment of Childhood Enuresis

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