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Combination therapy (desmopressin plus oxybutynin) improves the response rate compared with desmopressin alone in patients with monosymptomatic nocturnal enuresis and nocturnal polyuria and absence of constipation predict the response to this treatment

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Abstract

Combination therapy (CT) (desmopressin plus oxybutynin) has been considered for the treatment of monosymptomatic nocturnal enuresis (MNE). We designed our study with the aim to evaluate the response rate to CT compared with desmopressin alone (primary outcome) and to identify factors associated with the response to CT (secondary outcome). We prospectively enrolled children with MNE with absent/partial response after 3 months of evening treatment with 240 mcg of desmopressin. We defined the response rate to CT compared with desmopressin alone according to the standardization of terminology document of the International Children’s Continence Society: no-response, < 50% reduction; partial response, 50 to 99% reduction; and complete response, 100% reduction of wet nights. Both partial response and complete response to CT were clustered for the analyses of this manuscript. The enrolled children treated with 240 mcg/evening of desmopressin had also an additional evening administration of 0.3 mg/kg oxybutynin. A follow-up was scheduled at 3 and 6 months after the beginning of CT. At 3 months, oxybutynin dose was augmented to 0.5 mg/kg in case of absent/partial response to CT. Nocturnal diuresis was measured in 5 wet nights prior the beginning of therapy with desmopressin. Nocturnal polyuria (NP) was defined as nocturnal urine production > 130% of the expected bladder capacity. All patients with constipation were treated with macrogol. We enrolled 81 children (35.8% females) with a mean age of 8.4 ± 2.3 years. Seventy-eight patients completed the follow-up. After the CT, 59/78 (75.6%) patients showed an improvement of the response with CT compared with desmopressin alone. At multivariate analysis, both NP in more than 1 night (OR = 8.5; 95% CI, 1.4–51.6; p = 0.02) and absence of constipation (OR = 7.1; 95% CI, 1.6–31.0; p = 0.009) resulted significant after Bonferroni correction.

Conclusions: CT determines an improvement of response compared to therapy with desmopressin alone in 75.6% of patients. Significant predictive factors of response to CT were presence of NP and absence of constipation.

What is Known:

• Combination therapy (CT) (desmopressin plus anticholinergic drug) has been described as a therapeutic option for patients with monosymptomatic nocturnal enuresis (MNE) not responding to desmopressin alone as first-line treatment.

• Variable protocols and variable combination of drugs have been described with a response rate ranging from 44 to 76%.

What is New:

• We found that 59 patients (75.6%) treated with evening administration of 240 mcg of sublingual desmopressin plus 0.3–0.5 mg/kg of oxybutynin had an improvement of response compared to treatment with desmopressin alone.

• We add evidence that presence of frequently recurring nocturnal polyuria and absence of constipation are predictors of response to CT.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on request.

Code availability

N/A.

Abbreviations

BVWI:

Bladder volume and wall thickness index

CT:

Combination therapy

EBC:

Expected bladder capacity

FBC:

Functional bladder capacity

ICCS:

International Children’s Continence Society

LUTS:

Lower urinary tract symptoms

MNE:

Monosymptomatic nocturnal enuresis

MVV:

Maximum voided volume

NE:

Nocturnal enuresis

NMNE:

Non-monosymptomatic nocturnal enuresis

NP:

Nocturnal polyuria

OAB:

Overactive bladder

PVR:

Post-void residual urine

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Authors and Affiliations

  1. Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, Naples, 80138, Italy

    Daniela Capalbo, Stefano Guarino, Anna Di Sessa, Claudia Esposito, Carolina Grella, Alfonso Papparella, Emanuele Miraglia del Giudice & Pierluigi Marzuillo

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  1. Daniela Capalbo
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  2. Stefano Guarino
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  3. Anna Di Sessa
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  5. Carolina Grella
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  7. Emanuele Miraglia del Giudice
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  8. Pierluigi Marzuillo
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Contributions

Study concept and design: Capalbo, Marzuillo, and Guarino. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: Capalbo and Marzuillo. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: Marzuillo and Capalbo. Study supervision: Marzuillo, Di Sessa, Guarino, and Miraglia del Giudice.

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Correspondence to Stefano Guarino.

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Communicated by Peter de Winter.

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Capalbo, D., Guarino, S., Di Sessa, A. et al. Combination therapy (desmopressin plus oxybutynin) improves the response rate compared with desmopressin alone in patients with monosymptomatic nocturnal enuresis and nocturnal polyuria and absence of constipation predict the response to this treatment. Eur J Pediatr 182, 1587–1592 (2023). https://doi.org/10.1007/s00431-023-04824-5

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