Comparing Desmopressin Plus Anticholinergics Versus Desmopressin Alone for Monosymptomatic Nocturnal Enuresis: A Systematic Review and Meta-Analysis

Context: Monosymptomatic nocturnal enuresis (MNE) is the most common type of enuresis. Desmopressin is the most widely used pharmacological treatment for MNE, while combination therapy with anticholinergics is recommended for patients who are refractory to monotherapy. Objectives: This meta-analysis aims to evaluate the efficacy and safety of combination therapy (desmopressin with an anticholinergic agent) compared with desmopressin alone in the treatment of MNE. Methods: A comprehensive search was conducted across multiple databases, including Cochrane, Scopus, ScienceDirect, PubMed, and Embase, along with manual searching. Clinical trials were included in this meta-analysis, specifically focusing on the comparison between desmopressin combined with an anticholinergic agent and desmopressin alone in pediatric patients with MNE. The primary outcomes assessed were complete remission (90 - 100% reduction in mean wet nights compared to baseline) and partial remission (50 - 90% reduction), with the latter being considered as part of total remission (sum of complete and partial remission). The secondary outcome measured adverse effects. The risk of bias was evaluated using Cochrane tools, and a forest plot was generated using Review Manager 5.4. Results: Eleven studies involving 872 pediatric patients (aged 5 to 17 years) with MNE were included in this meta-analysis. The analysis assessed the efficacy of desmopressin combined with anticholinergics compared to desmopressin as monotherapy in achieving remission of enuresis at one month and three months after initiating therapy. Results demonstrated that combination therapy yielded favorable outcomes for enuresis remission. At one month, the risk ratio (RR) for complete remission favored combination therapy (RR: 1.52, 95% CI 1.14 - 2.02), as did the RR for total remission (RR: 1.15, 95% CI 1.02 - 1.30). However, both outcomes exhibited heterogeneity (I²: 71% and 59%, respectively). At three months, the combination therapy continued to show benefits, with a RR of 1.34 (95% CI 1.11 - 1.63) for complete remission and 1.10 (95% CI 1.00 - 1.21) for total remission, although the statistical significance was weaker (P = 0.003 and P = 0.05, respectively). Both treatment groups reported minor side effects. Conclusions: Combination therapy of desmopressin and anticholinergics showed favorable outcomes for enuresis remission. Further research is required to explore the long-term benefits and potential side effects.