Failure of monotherapy in primary monosymptomatic enuresis: a combined desmopressin and propiverine treatment regimen improves efficacy outcomes

Abstract

OBJECTIVE To evaluate, in a prospective study, the combination of the antimuscarinic propiverine and the antidiuretic hormone‐agonist desmopressin in children and adolescents not responsive to previous monotherapy, as in primary monosymptomatic enuresis (PME), combined treatments are considered a second‐line approach after the failure of monotherapy. PATIENTS AND METHODS The study included 122 children and adolescents (mean age 10.8 years, range 5–21) with PME and so far unresponsive to single or multiple monotherapy. Propiverine (body weight <30 kg, 15 mg/day; ≥30 kg, 20 mg/day) and desmopressin (0.4 mg/night) were administered over 3 months, followed by successive structured withdrawal programmes for propiverine and desmopressin, depending on the amount of loss of urine at night before treatment. RESULTS The re‐evaluation of unresponsive patients, incorporating video‐urodynamics, showed neurogenic detrusor overactivity, isolated detrusor sphincter dyssynergia and vesicorenal reflux in 12.3% (15/122) of patients, so far falsely treated as enuresis. In 107 of 122 patients the diagnosis of PME was confirmed. The primary efficacy outcome, continence at night, was achieved in 104 of 107 patients (97.2%). During the individual follow‐up periods (3–12 months), 23 of 107 (21.5%) patients relapsed after withdrawal of both medications. Adverse events of moderate intensity were rare (3.7%). CONCLUSION Re‐evaluation of patients after monotherapy has failed is justified, because other entities can be discovered in patients so far treated unsuccessfully for enuresis. The combination of propiverine and desmopressin is highly effective in children with PME. Our results support the case for further optimizing the inaugurated treatment algorithm of PME for treatment duration, dose‐titration and structured withdrawal programmes, thus possibly further decreasing relapse rates.

Desmopressin treatment regimens in monosymptomatic and nonmonosymptomatic enuresis: A review from a clinical perspective

“…children with neurogenic detrusor overactivity. The assumption of improving the preciseness of the clinical diagnosis by implementing a minor invasive diagnostic assessment is also in conformity with our clinical experience [36]; however, this approach should be restricted to non-responsive children.…”

“…A trend of superior short-and long-term success rates following a minor invasive diagnostic assessment resulted; however, these results are based on limited evidence and [12] 25 44.0% 8 must be interpreted with caution, because long-term success rates for ME [36] and NME [10] are reported in only one study each.…”

“…In ME, especially in cases refractory to desmopressin monotherapy [12,36], efficacy can be further improved by combining DDAVP with antimuscarinics. In NME compared to ME efficacy outcomes are improved to a greater extent with this treatment [54].…”

“…Even more impressive than the superior short-term success rates are the long-term success and relapse rates following antimuscarinics adjunct to desmopressin compared to desmopressin monotherapy (Table 7). These impressive outcomes in ME following adjunct treatment with antimuscarinics as compared to enuresis alarm might have been biased by the diagnostic algorithm: unfortunately, only one study implementing a minor invasive diagnostic assessment was reported for antimuscarinics as add-on treatment to desmopressin [36]. Varying degrees of invasiveness of the diagnostic assessment obviously present a co-variable possibly affecting success rates by introducing a population bias.…”

“…With regard to antimuscarinics in children, oxybutynin [56], propiverine [36,66], and tolterodine [12,67] can be compared. Study results of antimuscarinics administered in enuretics as adjunct to desmopressin are scarce.…”