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Reboxetine in therapy-resistant enuresis: a retrospective evaluation
Uppsala Univ, Childrens Hosp, Nephrol Unit.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.ORCID iD: 0000-0002-4590-4957
2009 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 5, p. 365-368Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Imipramine is the only evidence-based treatment available for enuretic children resistant to standard therapy. The drug's antienuretic effect is probably due to noradrenergic facilitation. The drug is, however, potentially cardiotoxic. In this study, the non-cardiotoxic noradrenergic antidepressant reboxetine was tested as an alternative to imipramine. PATIENTS AND METHODS: 61 patients, aged 7-19 years, with enuresis-resistant to desmopressin, the alarm, urotherapy and anticholinergics, were given 4-8 mg reboxetine at bedtime, if necessary combined with desmopressin. RESULTS: 32 patients became dry on reboxetine treatment, although 21 of them required combination treatment with desmopressin to achieve this. Eighteen children did not respond and eight children discontinued because of side-effects before treatment could be evaluated. No serious adverse events occurred. CONCLUSIONS: These results need to be confirmed with randomized controlled studies, but indicate that reboxetine will become a safe and efficient treatment alternative for enuretic children resistant to standard therapy.

Place, publisher, year, edition, pages
2009. Vol. 43, no 5, p. 365-368
Keywords [en]
Antidepressants, enuresis, reboxetine
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-113343DOI: 10.3109/00365590903099959ISI: 000272144300004PubMedID: 19921980OAI: oai:DiVA.org:uu-113343DiVA, id: diva2:290534
Available from: 2010-01-27 Created: 2010-01-27 Last updated: 2019-07-29
In thesis
1. Therapy-resistant enuresis: In search of new therapies and prognostic markers
Open this publication in new window or tab >>Therapy-resistant enuresis: In search of new therapies and prognostic markers
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A large minority of children with enuresis do not respond to treatment with either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment of enuresis, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. Since the long-term consequences of enuresis are potentially grave it is important that effective treatments of therapy-resistant enuresis are found.

When investigating the enuretic child a full voiding-chart - in addition to the case history - is the method of choice. However, there is no robust evidence that daytime voiding chart data actually do predict nocturnal detrusor function.

The aim of this thesis was to determine whether there is a role for the noradrenergic antidepressant reboxetine in the treatment of therapy-resistant enuresis, and whether anamnestic data and the voiding chart provides prognostic information regarding response to treatment with anticholinergics and antidepressants respectively in therapy-resistant patients.

In a retrospective evaluation of 61 children who for humanitarian purposes had been treated with reboxetine 32(52%) responded to this treatment, 21 of them after desmopressin had been added. We then proceeded with a randomized placebo-controlled study with 18 patients, in which the reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p=0.002). However, no patient achieved complete dryness. No prognostic markers for therapy-response were found in either of these studies.

In the randomized study we also sought to investigate whether reboxetine had any statistically significant effect on voiding-chart data. No such effect was found, but in respect to this secondary aim the sample size was too small. Nonetheless , this led to the speculation whether reboxetine exerts its antienuretic effect via modulation of arousal mechanisms.

Prognostic markers were sought in a retrospective evaluation of 154 patients treated with anticholinergics or antidepressants, but few and inconsistent differences were found between the groups responding or not responding to the various treatment regimens, and this was true both for anamnestic and voiding chart data.

In conclusion reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment, but further trials with higher doses and larger study populations are needed. The internationally recommended assessment of children with therapy-resistant enuresis does not seem to give the prognostic information intended.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1584
Keywords
Nocturnal enuresis, Reboxetine, Antidepressants, Desmopressin, Voiding chart
National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-389838 (URN)978-91-513-0701-5 (ISBN)
Public defence
2019-10-04, Enghoff-salen, Akademiska Sjukhuset, Ing 50 bv, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2019-09-12 Created: 2019-07-29 Last updated: 2019-10-15

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