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Structured cited links
Yuan Dai, Lingli Zhang, Juehua Yu, Xin Zhou, Yiting Ji, Kai Wang, Xiujuan Du, Xin Liu, et al. (2020). Improved symptoms following bumetanide treatment in children aged 3 to 6 years with autism spectrum disorder via GABAergic mechanisms: a randomized, double-blind, placebo-controlled trial. openRxiv.
Abstract
Abstract With the drug therapy for the core symptoms of autism spectrum disorder (ASD) currently limited, here we reported a randomised, double-blind, placebo-controlled trial to investigate the efficacy, safety, and potential neural mechanism of bumetanide in children with ASD aged 3 to 6 years old. In this trial, 120 children with ASD were 1:1 randomly assigned to receive 0.5 mg bumetanide or placebo orally twice daily for 3 months. The primary outcome was the score reduction of Childhood Autism Rating Scale (CARS) and the secondary outcomes were the score of Clinical Global Impressions (CGI) Improvement scale (CGI-I) at 3 months and the change from baseline to 3-month in Autism Diagnostic Observation Schedule (ADOS). Magnetic resonance spectroscopy (MRS) was used to measure γ-aminobutyric acid (GABA) and glutamate neurotransmitter concentrations in the insular cortex (IC) before and after the treatment. As compared with the placebo, bumetanide treatment was significantly better in reducing severity. No patient withdrew from the trial due to adverse events. The superiority of bumetanide to placebo in reducing insular GABA, measured using MRS, was demonstrated. The clinical improvement was associated with the decrease in insular GABA in the bumetanide group. In children with predominantly moderate and severe ASD, the treatment of bumetanide at a dose of 0.5 mg twice daily attenuated the core symptoms, as compared with placebo, with few adverse events. The neuroimaging data demonstrated that bumetanide decreased GABA levels in insular cortex, which was associated with symptom reduction.
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