Treatment guidelines for nocturnal enuresis (NE) in children had been proposed both in Japan and internationally. However, research on how children with NE are being treated in clinical settings is still limited. Therefore, we conducted a retrospective descriptive epidemiological study to examine prescribing patterns and trends of pharmacotherapy in childhood NE using a large-scale medical claims database in Japan.

The data were provided by Japan Medical Data Center, Inc. We selected patients who had at least two medical claims of International Classification of Diseases 10th revision code for unspecified urinary incontinence (ICD10: R32) between January 2005 and March 2019. Based on the Japanese standardized disease name assigned to this code, only patients who were diagnosed with NE or childhood NE were specifically included. For newly diagnosed cohort, we identified the oldest consultation date recorded assigned to each diagnostic claim. Medications were classified into three major categories: antidiuretic hormone (desmopressin acetate alone), anticholinergic drugs (such as oxybutynin and propiverine hydrochloride), and tricyclic antidepressants (such as imipramine and clomipramine hydrochloride). The annual trends were reported for the proportion of non-prescribing and the types of medications. The initial medication choice by class and its initial prescribed age were also analyzed.

During the study period, there were 23,814 registrants under 16 years old. A total of 3,494 children with NE were identified (mean age of 5.1±3.6 years) and a majority were males (66.0%). Comorbidities included neurogenic bladder (11.3%), overactive bladder (10.6%), and constipation (5.8%). The year-by-year transition in the proportions of children not being prescribed with NE medication is shown in Figure 1. Of those who were prescribed, the annual trend of prescribed medications for NE by drug class is summarized in Figure 2. (Please note that we did not plot data for 2019 in both figures as the data obtained for 2019 was until the end of March, not a full year.) Among the newly diagnosed children (n=2,998), the average age at which they were first prescribed with NE medications were desmopressin at 8.3±1.8 years, anticholinergic drugs at 8.1±2.1 years, and tricyclic antidepressants at 8.5±2.4 years. When dosage form alone was examined for desmopressin, the orodispersible tablet (83.5%) was preferred over nasal spray or drop. The most frequently prescribed anticholinergic drug and tricyclic antidepressant were propiverine hydrochloride (45.9%) and imipramine hydrochloride (75.0%), respectively.

Apart from the start year of the database (2005), the proportion of children being not prescribed with NE medications has generally decreased steadily from 93.0% in 2006 to 84.7% in 2018 (Figure 1). With respect to the type of medications prescribed, desmopressin remained the most frequently selected in the last five years (Figure 2), and orodispersible tablet form had been preferred rather than nasal drop or spray. Regardless of the class of medication, the initiation of prescribing pharmacological therapy was most frequently observed at around eight years old.

We revealed that the proportion of children being prescribed with NE medications was generally on the rise each year, and desmopressin was the most common choice. Further studies to estimate the impact of each pharmacotherapy, as well as the non-pharmacological interventions on children’s treatment outcomes, are expected to improve treatment selection.