The Safety and Efficacy of Fluoxetine for the Treatment of Refractory Primary Monosymptomatic Nocturnal Enuresis in Children: A Randomized Placebo-Controlled Trial.

Purpose: We investigated the efficacy and safety of fluoxetine, a selective serotonin reuptake inhibitor, for treating refractory primary monosymptomatic nocturnal enuresis in children.

Materials And Methods: Children 8-18 years old with severe primary monosymptomatic nocturnal enuresis unresponsive to alarm therapy, desmopressin, and anticholinergics were screened for eligibility. After excluding children with daytime urinary symptoms, constipation, underlying urological, neuropsychiatric, endocrinological, or cardiac conditions, patients were randomly and equally assigned to 10 mg fluoxetine once daily or placebo for 12 weeks. The primary outcome was treatment response according to the International Children's Continence Society terminology. Treatment-related adverse effects and nighttime arousal were secondary outcomes.

Results: A total of 150 children were enrolled, of whom 110 (56 in fluoxetine group and 54 in placebo group) with a mean age of 11.8 (SD 2.46) years were finally analyzed. After 4 weeks, 7.1% and 66.1% of the fluoxetine group achieved complete response and partial response (defined as 50%-99% reduction of the number of wet nights), respectively, versus 0% and 16.7% of the placebo group ( < .001). At 12 weeks, complete and partial responses were achieved in 10.7% and 21.4% of the fluoxetine group, respectively (vs 0% and 14.8% of the placebo group, = .023). Fluoxetine-treated patients had fewer wet nights (4.7 [SD 4.2] fortnightly vs 9.7 [SD 3.5] at 4 weeks, < .001; 5.7 [SD 4.4] vs 9.9 [SD 3.4] at 8 weeks, < .001; 7.5 [SD 4.6] vs 9.9 [SD 3.4] at 12 weeks, = .003). Fluoxetine was associated with improved nighttime arousal ( = .017), and minor and rapidly reversible adverse effects in 5 (8.9%) patients.

Conclusions: Fluoxetine is safe treatment for refractory primary monosymptomatic nocturnal enuresis in children with good initial response that declines at 12 weeks.