Treatment Outcomes of Combined Solifenacin and Desmopressin Therapy Compared with Desmopressin Monotherapy in Children with Primary Monosymptomatic Nocturnal Enuresis: A Prospective Cohort Study

Primary monosymptomatic nocturnal enuresis (PMNE), defined as intermittent nocturnal urinary incontinence during sleep in children aged five years or older in the absence of daytime lower urinary tract symptoms or bladder dysfunction, is one of the most common pediatric urological disorders. Although the condition demonstrates a spontaneous annual remission rate of approximately 15%, PMNE continues to affect a substantial proportion of school-aged children and adolescents, making it an important public health concern. Beyond the physical symptom of nocturnal bedwetting, PMNE exerts considerable psychosocial consequences, including reduced self-esteem, embarrassment, anxiety, impaired social functioning, and diminished health-related quality of life. These effects frequently extend to parents and caregivers, contributing to emotional stress, disrupted family routines, increased healthcare utilization, and additional financial burden. Given its high prevalence and significant impact on children and their families, timely diagnosis and effective treatment remain essential components of pediatric clinical practice (1,2).

 The pathophysiology of PMNE is multifactorial and reflects the interaction of several physiological mechanisms. The principal contributors include nocturnal polyuria resulting from inadequate nocturnal secretion of arginine vasopressin, reduced functional bladder capacity, nocturnal detrusor overactivity, impaired arousal from sleep despite bladder fullness, and delayed maturation of the central nervous system pathways involved in bladder control. Genetic susceptibility and sleep-related factors have also been implicated in disease development. Consequently, contemporary management emphasizes individualized treatment according to the predominant underlying mechanism. Standard treatment includes education and reassurance, behavioral and lifestyle modification, fluid management, treatment of constipation where appropriate, enuresis alarm therapy, and pharmacological intervention. Among pharmacological options, desmopressin, a synthetic analogue of arginine vasopressin, is recommended as a first-line therapy, particularly for children with nocturnal polyuria. By reducing nocturnal urine production through enhanced renal water reabsorption, desmopressin rapidly decreases the frequency of wet nights and provides symptomatic relief for many patients. However, a considerable proportion of children demonstrate only partial response or fail to achieve complete dryness, and relapse following treatment discontinuation remains a well-recognized limitation of desmopressin monotherapy (1,3,7).

 Recognition of the heterogeneous pathophysiology of PMNE has stimulated increasing interest in combination pharmacotherapy targeting multiple mechanisms simultaneously. Solifenacin, a selective muscarinic M3 receptor antagonist, improves bladder storage by inhibiting involuntary detrusor contractions and increasing functional bladder capacity. Although primarily indicated for overactive bladder, it may also benefit children with PMNE in whom reduced nocturnal bladder capacity contributes to persistent symptoms. The combination of solifenacin with desmopressin is therefore biologically plausible because it simultaneously addresses nocturnal polyuria and impaired bladder storage function. Emerging evidence from randomized clinical trials and systematic reviews suggests that combination therapy may result in higher complete response rates, fewer wet nights, and greater overall treatment success than desmopressin alone without a significant increase in adverse events. Nevertheless, variations in study populations, treatment protocols, outcome definitions, and follow-up periods have resulted in inconsistent findings, and the overall evidence remains insufficient to establish combination therapy as the preferred initial pharmacological approach for all children with PMNE (3–6,10).

 Despite encouraging evidence supporting combined therapy, important gaps remain in the current literature. Many published studies have involved relatively small sample sizes, retrospective designs, or heterogeneous patient populations, limiting the generalizability of their findings. Furthermore, prospective comparative studies evaluating the effectiveness of combined solifenacin and desmopressin therapy against desmopressin monotherapy remain limited, particularly in resource-limited settings where treatment decisions must balance efficacy, safety, and cost. Additional prospective evidence is therefore required to clarify the comparative effectiveness of these treatment strategies, optimize patient selection, and strengthen the evidence base informing clinical practice guidelines. Such evidence may contribute to improved therapeutic outcomes and facilitate more individualized management of children with PMNE.

A total of 100 children diagnosed with primary monosymptomatic nocturnal enuresis were enrolled in this prospective cohort study, with 50 participants receiving desmopressin monotherapy and 50 receiving combined solifenacin and desmopressin therapy. All participants met the eligibility criteria and were included in the final analysis. Follow-up was completed by 96 participants (96.0%), while four participants (4.0%) were lost to follow-up.

 Baseline Characteristics

The baseline demographic and clinical characteristics of the study participants are presented in Table 1. The mean age was comparable between the desmopressin monotherapy and combination therapy groups (9.22 ± 2.83 vs. 9.42 ± 2.88 years, p = 0.727). Although males predominated in both groups, the difference in sex distribution was not statistically significant (64.0% vs. 82.0%, p = 0.072). No statistically significant differences were observed between the groups regarding weight, height, body mass index, duration of enuresis, age at onset, baseline frequency of wet nights, family history of enuresis, previous treatment, constipation, deep sleeping, or snoring (all p > 0.05), indicating that the two cohorts were comparable before treatment initiation.

  Table 1. Baseline Demographic and Clinical Characteristics of Children with Primary Monosymptomatic Nocturnal Enuresis According to Treatment Group.

 Treatment Outcomes

Treatment outcomes following 12 weeks of therapy are summarized in Table 2. Children treated with combined solifenacin and desmopressin therapy demonstrated significantly greater improvement than those receiving desmopressin monotherapy. The mean number of wet nights per week was significantly lower in the combination therapy group at Week 4 (3.46 ± 1.18 vs. 4.58 ± 1.32, p < 0.001), Week 8 (1.64 ± 1.09 vs. 3.22 ± 1.41, p < 0.001), and Week 12 (0.62 ± 0.81 vs. 2.10 ± 1.36, p < 0.001). Similarly, the mean percentage reduction in wet nights was significantly greater among children receiving combination therapy (88.7% ± 18.6%) than among those receiving desmopressin monotherapy (63.4% ± 22.8%, p < 0.001). The combination therapy group also experienced a shorter mean time to clinical improvement (3.9 ± 1.4 weeks vs. 5.8 ± 1.7 weeks, p < 0.001).

Table 2. Comparison of Treatment Outcomes Between Desmopressin Monotherapy and Combined Solifenacin + Desmopressin Therapy

Based on the International Children's Continence Society response criteria, complete response was achieved by 13 (26.0%) children in the combination therapy group compared with 4 (8.0%) in the monotherapy group. Partial response was observed in 35 (70.0%) and 22 (44.0%) participants, respectively, whereas non-response occurred in only 2 (4.0%) children receiving combination therapy compared with 24 (48.0%) children receiving desmopressin monotherapy (p < 0.001).

Treatment Adherence and Safety

Treatment adherence and safety outcomes are presented in Table 3. Children receiving combination therapy demonstrated significantly higher medication adherence than those receiving desmopressin monotherapy (93.8 ± 4.8% vs. 89.4 ± 5.6%, p < 0.001) and reported significantly fewer missed doses (5.2 ± 3.1 vs. 8.6 ± 4.5, p < 0.001). Parent satisfaction scores were also significantly higher in the combination therapy group (4.5 ± 0.7 vs. 3.2 ± 0.9, p < 0.001).

Table 3. Comparison of Treatment Adherence, Safety Profile, and Follow-up Outcomes Between the Two Treatment Groups

Adverse events were uncommon in both treatment groups and did not differ significantly between participants receiving combination therapy and those receiving desmopressin monotherapy (14.0% vs. 8.0%, p = 0.337). Treatment discontinuation was rare, occurring in one participant in each group (2.0%, p = 1.000). Follow-up completion exceeded 90% in both treatment groups, with no statistically significant difference observed between groups (98.0% vs. 94.0%, p = 0.617).

Multivariable Logistic Regression Analysis

The results of the multivariable logistic regression analysis are presented in Table 4. After adjustment for age, sex, duration of enuresis, baseline frequency of wet nights, family history of enuresis, deep sleeping, and treatment adherence, combined solifenacin and desmopressin therapy remained independently associated with a significantly greater likelihood of achieving complete treatment response compared with desmopressin monotherapy (adjusted odds ratio [AOR] = 4.89; 95% confidence interval [CI]: 1.42–16.86; p = 0.012). Higher treatment adherence was also independently associated with complete response (AOR = 1.09; 95% CI: 1.02–1.17; p = 0.014). None of the remaining demographic or clinical variables demonstrated statistically significant independent associations with treatment success.

Table 4. Multivariable Logistic Regression Analysis of Factors Associated with Complete Treatment Response in Children with Primary Monosymptomatic Nocturnal Enuresis (N = 100)

The present prospective cohort study demonstrated that combined solifenacin and desmopressin therapy was associated with superior clinical outcomes compared with desmopressin monotherapy in children with primary monosymptomatic nocturnal enuresis (PMNE). Children receiving combination therapy experienced significantly greater reductions in nocturnal enuretic episodes, higher complete treatment response rates, earlier clinical improvement, and better medication adherence and parent satisfaction. Importantly, these improved outcomes were achieved without a significant increase in adverse events or treatment discontinuation. These findings are clinically relevant because successful management of PMNE extends beyond reducing bedwetting episodes to improving psychological well-being, self-esteem, social functioning, and family quality of life.

 The findings of the present study are consistent with accumulating evidence supporting combination pharmacotherapy for PMNE. Ahmad and Minallah reported significantly higher treatment success and complete response rates among children receiving combined solifenacin and desmopressin therapy compared with desmopressin alone, without a clinically meaningful increase in adverse events (12). Similarly, Ghanavati et al. demonstrated that both solifenacin–desmopressin and tolterodine–desmopressin combinations achieved greater reductions in wet nights and higher response rates than desmopressin monotherapy while maintaining acceptable tolerability (13). The present findings closely parallel these randomized clinical trials, reinforcing the concept that simultaneously targeting multiple pathophysiological mechanisms provides greater therapeutic benefit than treating nocturnal polyuria alone.

 Additional support is provided by the randomized clinical trial conducted by Cho et al., who demonstrated that adding an anticholinergic agent to desmopressin significantly improved treatment outcomes while increasing functional bladder capacity (14). These findings are particularly important because reduced nocturnal bladder capacity has been recognized as a major contributor to persistent symptoms in many children with PMNE. Furthermore, a network meta-analysis by Song et al. concluded that combination therapy involving desmopressin and anticholinergic agents consistently produced superior therapeutic outcomes compared with desmopressin monotherapy, with no substantial increase in adverse effects (15). Unlike randomized controlled trials conducted under highly controlled conditions, the present study reflects routine clinical practice in a tertiary-care pediatric urology center, thereby providing complementary real-world evidence supporting the effectiveness and safety of combination therapy.

The biological plausibility of these findings is supported by the current understanding of PMNE pathophysiology. The International Children's Continence Society (ICCS) recognizes PMNE as a multifactorial disorder resulting from nocturnal polyuria, reduced functional bladder capacity, detrusor overactivity, impaired arousal from sleep, and delayed maturation of bladder control mechanisms (11). Likewise, the European Association of Urology recommends that treatment should be individualized according to the predominant underlying pathophysiological mechanism rather than adopting a uniform therapeutic strategy (17). Desmopressin effectively reduces nocturnal urine production through its antidiuretic action but does not address impaired bladder storage function (11). In contrast, solifenacin selectively blocks muscarinic M3 receptors, suppressing involuntary detrusor contractions and increasing functional bladder capacity. The complementary mechanisms of these two agents provide a logical explanation for the greater reductions in wet nights, higher complete response rates, and earlier symptom improvement observed in the combination therapy group (11,14,17).

The findings of the present study have important implications for contemporary clinical practice. Current international guidelines advocate individualized management of PMNE based on the predominant underlying pathophysiological mechanism rather than a uniform treatment approach for all patients (11,17). The superior clinical outcomes observed with combined solifenacin and desmopressin therapy suggest that children with persistent nocturnal enuresis, particularly those with an inadequate response to desmopressin monotherapy or reduced functional bladder capacity, may benefit from combination treatment. Earlier symptom control may reduce the psychological burden associated with persistent bedwetting, improve medication adherence, and enhance parental confidence in treatment. These findings are particularly relevant for pediatric urologists, pediatric nephrologists, and general pediatricians. In low- and middle-income countries such as Pakistan, where access to specialized behavioral interventions, including enuresis alarm therapy, may be limited, an effective pharmacological strategy capable of producing rapid and sustained symptom improvement may represent a practical alternative (11,17).

 Several strengths enhance the validity of the present study. The prospective cohort design enabled systematic longitudinal assessment of treatment outcomes while minimizing recall bias. Diagnosis was established according to standardized ICCS criteria, ensuring consistency with international recommendations and facilitating comparison with previous studies (11). Both treatment groups were managed within the same tertiary-care center using standardized treatment protocols and follow-up schedules, thereby reducing variation in clinical practice. Furthermore, treatment effectiveness was assessed using multiple clinically relevant outcomes, including reduction in wet nights, ICCS response categories, medication adherence, parent satisfaction, and adverse events, providing a comprehensive evaluation of both efficacy and tolerability. The high follow-up completion rate further strengthened the internal validity of the study.

 Nevertheless, several limitations should be acknowledged. First, the single-center design may limit the generalizability of the findings to other populations and healthcare settings. Second, although the sample size was adequate to detect clinically meaningful differences between treatment groups, larger studies are needed to improve the precision of effect estimates. Third, treatment allocation was based on routine clinical practice rather than randomization, introducing the possibility of selection bias and residual confounding despite multivariable adjustment. In addition, the 12-week follow-up period did not permit evaluation of long-term treatment durability or relapse after treatment discontinuation, which remains an important consideration in PMNE management (11). Finally, objective assessments of functional bladder capacity, nocturnal urine production, sleep quality, and validated quality-of-life measures were not incorporated, limiting further exploration of the mechanisms underlying treatment response.

 Future research should focus on adequately powered multicenter randomized controlled trials comparing combination therapy with desmopressin monotherapy across diverse populations. Longer follow-up is needed to evaluate sustained treatment success, relapse rates, and long-term medication adherence (13,15). Future investigations should also incorporate validated patient-reported outcome measures, standardized bladder diaries, and health-related quality-of-life assessments to provide a more comprehensive evaluation of treatment effectiveness. In addition, cost-effectiveness analyses are warranted, particularly in resource-limited settings, to determine whether the improved clinical outcomes associated with combination therapy justify additional treatment costs. Research exploring clinical predictors and biomarkers of treatment response may also facilitate more personalized therapeutic strategies for children with PMNE (11,17).

 In conclusion, this prospective cohort study demonstrated that combined solifenacin and desmopressin therapy was associated with superior clinical effectiveness compared with desmopressin monotherapy in children with PMNE. Combination therapy resulted in greater reductions in nocturnal enuretic episodes, higher treatment response rates, earlier clinical improvement, better medication adherence, and greater parent satisfaction while maintaining an acceptable safety profile. Although confirmation through larger multicenter randomized trials with longer follow-up is required (13,15), the present findings support consideration of combination therapy as an effective treatment option for appropriately selected children with PMNE, particularly those who fail to achieve satisfactory symptom control with desmopressin monotherapy (11,17).

In this prospective cohort study, combined solifenacin and desmopressin therapy was associated with superior clinical outcomes compared with desmopressin monotherapy in children with primary monosymptomatic nocturnal enuresis. Children receiving combination therapy experienced greater reductions in the frequency of nocturnal enuretic episodes, higher treatment response rates, earlier clinical improvement, better medication adherence, and greater parent satisfaction, while maintaining an acceptable safety profile with no significant increase in adverse events. These findings support the concept that simultaneously targeting nocturnal polyuria and impaired bladder storage capacity may provide greater therapeutic benefit than addressing nocturnal polyuria alone. Although the observational design precludes causal inference and the findings should be interpreted in light of the study limitations, the results suggest that combined solifenacin and desmopressin therapy may be considered a valuable treatment option for appropriately selected children with primary monosymptomatic nocturnal enuresis, particularly those with an inadequate response to desmopressin monotherapy. Further large-scale, multicenter randomized controlled trials with longer follow-up are warranted to confirm these findings, evaluate long-term efficacy and relapse rates, and further define the role of combination therapy in the routine management of primary monosymptomatic nocturnal enuresis.

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5.      Cho SY, Kim SO, Yu HS, Kwon D, Park K, Ryu DS, et al. Effect of desmopressin lyophilisate plus anticholinergic combination on functional bladder capacity and therapeutic outcome as the first-line treatment for primary monosymptomatic nocturnal enuresis: a randomized clinical trial. Investig Clin Urol. 2021;62(3):331-338.

6.      Ahmad T, Minallah N. Comparative analysis of solifenacin plus desmopressin versus desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis. J Pediatr Surg. 2023;58(10):2034-2037.

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10.   Song P, Huang C, Wang J, et al. Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agents in the management of pediatric monosymptomatic nocturnal enuresis: a network meta-analysis. BJU Int. 2019;123(3):388-400.

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12.   Park SJ, Park JM, Pai KS, Ha TS, Lee SD, Baek M, et al. Desmopressin alone versus desmopressin and an anticholinergic in the first-line treatment of primary monosymptomatic nocturnal enuresis: a multicenter study. Pediatr Nephrol. 2014;29(7):1195–1200.

13.   Ahmad T, Minallah N. Comparative analysis of solifenacin plus desmopressin versus desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis. J Pediatr Surg. 2023;58(10):2034–2037.

14.   Ghanavati PM, Khazaeli D, Amjadzadeh M. A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone: a randomized controlled clinical trial. Int Braz J Urol. 2021;47(1):73–81.

15.   Cho SY, Kim SO, Yu HS, Kwon D, Park K, Ryu DS, et al. Effect of desmopressin lyophilisate plus anticholinergic combination on functional bladder capacity and therapeutic outcome as the first-line treatment for primary monosymptomatic nocturnal enuresis: a randomized clinical trial. Investig Clin Urol. 2021;62(3):331–338.

16.   Song P, Huang C, Wang J, et al. Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agents in the management of pediatric monosymptomatic nocturnal enuresis: a network meta-analysis. BJU Int. 2019;123(3):388–400.

17.   Austin PF, Ferguson G, Yan Y, et al. Combination therapy with desmopressin and anticholinergic medication for refractory monosymptomatic nocturnal enuresis in children. (

18.   Lee T, Suh HJ, Lee HJ, et al. Clinical outcomes of anticholinergic combination therapy in children with monosymptomatic nocturnal enuresis refractory to desmopressin.