Hussiny M, Hashem A, Soltan MA, Helmy TE, El-Kenawy MR, Abdelhalim A. The safety and efficacy of fluoxetine for the treatment of refractory primary monosymptomatic nocturnal enuresis in children: a randomized placebo-controlled trial. J Urol. 2022;208(5):1126-1134.

Study Need and Importance

Therapeutic options for treatment-refractory nocturnal enuresis (NE) are limited. A handful of studies suggested a possible role for selective serotonin reuptake inhibitors. In this randomized controlled trial, we examined fluoxetine (a selective serotonin reuptake inhibitor) as a treatment option for refractory NE.

What We Found

A total of 150 children aged 8-18 years with NE unresponsive to traditional therapies were enrolled after excluding patients with daytime symptoms, untreated constipation, or underlying developmental, neuropsychiatric, endocrinological, or urological comorbidities. Patients were randomly assigned to 10 mg fluoxetine once daily or placebo for 12 weeks. Fluoxetine-treated patients had a significantly lower number of wet nights at 4, 8, and 12 weeks relative to placebo (see Figure). According to the International Children’s Continence Society terminology, 7.1% and 66.1% of fluoxetine-treated patients achieved complete response and partial response (defined as 50%-99% reduction in the number of wet nights), respectively, at 4 weeks, versus 0% and 16.7% for placebo. Treatment response declined at 12 weeks, with complete and partial responses achieved in 10.7% and 21.4% of the fluoxetine group, respectively, versus 0% and 14.8% of the placebo group. Minor and rapidly reversible adverse effects were reported in 8.9% of fluoxetine-treated children.

Limitations

The study is limited by short follow-up. Some patients were lost to follow-up after the study conclusion, and therefore relapse rates after treatment discontinuation were not reported. The study included only patients with monosymptomatic NE without other comorbidities. Further studies should examine fluoxetine efficacy and safety in other patient populations including those with polysymptomatic enuresis and attention-deficit/hyperactivity disorder. It remains unknown if patients unresponsive or partially responsive to fluoxetine would benefit from higher doses of fluoxetine or combination with other anti-enuresis medications.

Interpretation for Patient Care

Fluoxetine could be considered a salvage treatment in children with treatment-refractory NE with good initial response and minimal adverse effects, but the response rate declines gradually over time.