Bumetanide

Because bumetanide is already FDA-approved, it may allow relatively rapid translation into clinical trials for people with Down syndrome. The bumetanide target dose in the trial is 0.02 mg/kg twice daily, administered orally morning and evening, with a half-dose titration period in the first week. Phase III trials of bumetanide 0.5 mg twice daily in ASD failed to demonstrate efficacy. A meta-analysis of six randomised placebo-controlled trials in 496 children with ASD found bumetanide significantly improved social affect and repetitive behaviours but not sensory symptoms. Bumetanide is a known diuretic and high-affinity antagonist of the NKCC1 cotransporter. Hypokalaemia is the most frequently observed adverse effect in bumetanide-treated patients. Bumetanide has been investigated in numerous neurodevelopmental and neurological conditions involving chloride homeostasis dysregulation, including ASD, Rett syndrome, epilepsy, and neonatal seizures.