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

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. 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. 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%). 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.