Journal Article

A randomised controlled trial of bumetanide in the treatment of autism in children

Hadjikhani, N, Ben-Ari, Y, Grandgeorge, M, Josse, F, Degrez, C, Tyzio, R, Lemonnier, E, Phelep, M

2012

Overview

Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study, 1 we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3–11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90−D0; P <0.004 treated vs placebo), Clinical Global Impressions ( P <0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean±s.d.; n =9) were removed (Wilcoxon test: P -value=0.031; Student’s t -test: P -value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0–3.5 mM l −1 K + ) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al. , submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
• Subject: 631/154/436/108 / 692/699/476/1312 / 692/700/1720 / Asperger Syndrome - drug therapy / Autistic Disorder - diagnosis / Autistic Disorder - drug therapy / Autistic Disorder - psychology / Behavioral Sciences / Biological Psychology / Bumetanide - therapeutic use / Child / Child, Preschool / Double-Blind Method / Female / GABA Modulators - therapeutic use / Humans / Male / Medicine / Medicine & Public Health / Neurosciences / Original / original-article / Pharmacotherapy / Psychiatry / Severity of Illness Index / Treatment Outcome