Medline ® Abstracts for References 55-59
of 'Nocturnal enuresis in children: Management'
Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial.
Austin PF, Ferguson G, Yan Y, Campigotto MJ, Royer ME, Coplen DE
OBJECTIVE: Desmopressin is an approved medical therapy for the treatment of monosymptomatic primary nocturnal enuresis. In cases of limited response to desmopressin, we have added anticholinergic therapy to desmopressin (combination therapy). To evaluate this treatment strategy, we examined the efficacy of combination therapy for primary nocturnal enuresis in desmopressin-nonresponders.
METHODS: Only patients with primary nocturnal enuresis refractory to the maximal dosage of desmopressin were enrolled. Children with lower urinary tract symptoms or bowel dysfunction were excluded, on the basis of a 3-day, 24-hour, frequency-volume chart and elimination record. Children continued to take desmopressin and were assigned randomly, in a double-blind manner, to receive either extended-release anticholinergic medication or placebo. Patients were reassessed after 1 month of therapy, with a 1-week nocturnal record.
RESULTS: Forty-one desmopressin-nonresponders were enrolled, and 7 patients were excluded because of noncompliance. The treatment groups were equally matched with respect to age, gender, functional bladder capacity, and number of wet nights per week. After 1 month of treatment, there was a significant reduction in the mean number of wet nights in the combination therapy group, compared with the placebo group. With a generalized estimating equation approach, there was a significant 66% decrease in the risk of a wet episode, compared with the placebo group.
CONCLUSIONS: This study represents the first prospective, placebo-controlled trial examining the effect of desmopressin in combination with long-acting, anticholinergic, bladder-relaxing therapy for monosymptomatic primary nocturnal enuresis.
Division of Urology, Washington University School of Medicine, St Louis Children's Hospital, St Louis, Missouri, USA. firstname.lastname@example.org
Combination therapy in the treatment of persistent nocturnal enuresis.
Cendron M, Klauber G
Br J Urol. 1998;81 Suppl 3:26.
OBJECTIVE: To evaluate, in a retrospective study, the response rate of older children to combination therapy using a sustained-release anticholinergic agent, hyoscyamine, and a synthetic analogue of antidiuretic hormone, desmopressin acetate.
PATIENTS AND METHOD: Twenty-eight patients (20 males and eight females, aged 9-18 years) diagnosed with nocturnal enuresis were evaluated using a questionnaire, history and physical examination. None had success with single-agent pharmacological therapy. All were begun on 0.375 mg of hyoscyamine and 20 microg of desmopressin intranasally at bedtime. The response rate was monitored at 2 and 4 weeks, and then every 3 months by recording dry nights on a calendar. To improve efficacy, the dosage of medication was adjusted up to 0.750 mg of hyoscyamine and 60 microg of desmopressin. Upon achieving dryness and spontaneous awakening to void, medication doses were tapered.
RESULTS: Within 6 months 16 (57%) patients were completely dry and six (21%) were dry at least 80% of nights. Nine patients relapsed during dose tapering and therapy was reinstituted. Presently, 17 (60%) patients are off medication (after a mean of 8 months of medication). Eight patients arestill on medication and are dry at least 80% of nights. Combination therapy failed in three patients and they have transferred to a different regimen. None experienced untoward side-effects from the medications.
CONCLUSION: Most older children with nocturnal enuresis responded to combination therapy. These children require long-term follow-up and may need medication for up to 6 months because the relapse rate is fairly high. Combination therapy appears safe and reliable in treating nocturnal enuresis in older children who have had no success with other treatment modalities.
Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Oxybutynin, desmopressin and enuresis.
J Urol. 2001;166(6):2459.
PURPOSE: A review of the scarce literature concerning oxybutynin treatment for nocturnal enuresis reveals that its success is greatest when enuresis is combined with daytime incontinence. The renal and bladder related characteristics of children with monosymptomatic enuresis responsive to oxybutynin were evaluated.
MATERIALS AND METHODS: Renal concentrating capacity and functional bladder capacity were compared between 55 dry children who served as controls, and children with monosymptomatic enuresis who responded to desmopressin only (group 1, 27), oxybutynin only (group 2, 11), combination desmopressin and oxybutynin (group 3, 7) or were resistant to all treatment alternatives (group 4, 23).
RESULTS: Renal concentrating capacity was lowest in groups 1 and 3 (939 +/- 147 mOsm./kg. controls, 856 +/- 158 group 1, 1,073 +/- 71 group 2, 762 +/- 119 group 3 and 970 +/- 146 group 4; p<0.01), whereas they had high urinary output (15.4 +/- 73.4 ml./kg. per hour controls, 22.2 +/- 10.2 group 1, 13.5 +/- 4.3 group 2, 21.5 +/- 11.2 group 3 and 15.0 +/- 6.9 group 4; p<0.01). Forced functional bladder capacity of that expected for age was lowest in groups 2 to 4 (107 +/- 43% controls, 88 +/- 43 group 1, 71 +/- 25 group 2, 68 +/- 22 group 3 and 59 +/- 22 group 4; p<0.01).
CONCLUSIONS: Children responding to oxybutynin have small bladders and probably hyperactive detrusors, whereas those responding to desmopressin or who need both drugs to achieve dryness have polyuria.
Uppsala University Children's Hospital, Uppsala, Sweden.
Desmopressin resistant enuresis: pathogenetic and therapeutic considerations.
Nevéus T, Läckgren G, Tuvemo T, Olsson U, Stenberg A
J Urol. 1999;162(6):2136.
PURPOSE: We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication.
MATERIALS AND METHODS: We gave 33 children with monosymptomatic nocturnal enuresis resistant to the standard 0.4 mg. oral dose of desmopressin 0.4 and 0.8 mg. desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion. The time of enuresis or nocturia was documented. All 9 children who had at least 1 dry treatment period during the randomized portion of the study then received open label treatment with 0.8 mg. desmopressin. Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment.
RESULTS: Average time between bedtime and voiding was 5.0, 5.6 and 5.0 hours during the nights with placebo, and 0.4 and 0.8 mg. desmopressin, respectively (p = 0.12). Of the 9 children subsequently treated with 0.8 mg. desmopressin 5 became completely dry. Of the remaining 28 children given anticholinergic treatment 20 responded.
CONCLUSIONS: Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis. This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability. A subgroup of enuretic children responds to high but not normal doses of desmopressin.
Department of Pediatrics, Uppsala University Children's Hospital, Swedish Agricultural University.
The role of bladder capacity in antidiuretic and anticholinergic treatment for nocturnal enuresis.
Radvanska E, Kovács L, Rittig S
J Urol. 2006;176(2):764.
PURPOSE: We evaluated combination treatment with desmopressin and oxybutynin in patients with enuresis who did not respond to desmopressin monotherapy. Furthermore, we compared 2 methods of estimating bladder capacity and evaluated the ability of these methods to predict the response to desmopressin and oxybutynin.
MATERIALS AND METHODS: A total of 60 children with a mean age +/- SD of 10.6 +/- 3.0 years who had monosymptomatic nocturnal enuresis completed the study. After a 2-week observation period maximal voided volume during free access to fluid intake was determined by a 2-day frequency-volume chart and maximal voided volume after water load was determined on a separate day. Patients then received 20 mug desmopressin intranasally at bedtime during 2 weeks. In nonresponders to desmopressin with less than a 50% decrease in wet nights 5 mg oxybutynin twice daily was added for another 2 weeks.
RESULTS: Of the patients 41 (68%) showed more than 50% decrease in wet nights during the 2-week desmopressin treatment period (4.6 +/- 1.6 to 0.7 +/- 0.8, p<0.001). In desmopressin nonresponders combined treatment with desmopressin and oxybutynin resulted in a further decrease in wet nights (4.0 +/- 1.2 to 1.7 +/- 1.4, p<0.001). Maximal voided volume during free access to fluid intake was significantly higher in desmopressin responders than in nonresponders (244 +/- 111 vs 160 +/- 65 ml, p<0.001). In contrast, maximal voided volume after water load was not significantly different between desmopressin responders and nonresponders.
CONCLUSIONS: The study indicates a role for oxybutynin in combination with desmopressin in children who are not responding to desmopressin monotherapy. Maximal voided volume during free access to fluid intake is a clinically useful predictor of the response to desmopressin but not to oxybutynin.
Department of Pediatrics, Comenius University Medical School, Bratislava, Slovakia.