For a study, researchers looked into how well fluoxetine (a selective serotonin reuptake inhibitor) worked and how safe it was for children with recalcitrant primary monosymptomatic nocturnal enuresis (PMNE). Eligible children ranged in age from 8 to 18, and they all suffered from severe PMNE that did not improve with alarm therapy, desmopressin, or anticholinergics. Subjects were randomly assigned to receive either 10 mg of fluoxetine once a day or a placebo for 12 weeks. Those with daytime urinary symptoms, constipation and underlying urological, neuropsychiatric, endocrinological, or cardiac problems were disqualified. Treatment response, as defined by the International Children’s Continence Society, was the key measure of success. Secondary outcomes included treatment-related side effects and insomnia. A total of 150 kids signed up, but only 110 were studied (56 in the fluoxetine group and 54 in the placebo group), with a mean age of 11.8 (SD 2.46). After 4 weeks, 7.1% of the fluoxetine group and 66.1% of the placebo group had a full response and a 50%-99% reduction in wet nights, respectively (P<.001). Complete and partial responses were attained by 10.7% and 21.4% of the fluoxetine group, respectively, at 12 weeks (vs. 0% and 14.8% of the placebo group, P =.023). Treatment with fluoxetine was associated with a decrease in the number of wet nights experienced by patients (4.7 [SD 4.2] biweekly vs. 9.7 [SD 3.5] at 4 weeks, P <.001; median [SD 4.4] 5.7 [SD 4.4] vs. 9.9 [SD 3.4] at 8 weeks, P <.001; median [SD 4.6] 7.5 [SD 4.6] v.s 9.9 [SD 3.4] at 12 weeks, P=.003). About 5 (8.9%) individuals reported experiencing modest, short-lived side effects from taking fluoxetine; however, the drug was related with better nightly arousal (P =.017). For children who haven’t improved after 12 weeks of treatment for refractory primary monosymptomatic nocturnal enuresis, fluoxetine is an effective and safe option.