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Bumetanide for Autism Spectrum Disorder: Current Evidence

Autism spectrum disorder (ASD), a lifelong neurodevelopmental disability characterized by persistent defects at social interactions and restricted behaviors and interests, affects 1 in every 59 children while effective treatment options are yet to be identified (1). Novel treatment options including gluten-free diet, vitamin and mineral supplementation have been implemented along with pharmacotherapy with limited success. Bumetanide is a loop diuretic drug that works by inhibiting sodiumpotassium-chloride (Na-K-Cl) cotransporters, namely NKCC1 and NKCC2, while NKCC1 is also present in brain in contrast to kidney-specific NKCC2 (2). Use of bumetanide in ASD patients was first proposed in 2010 in five infants treated with 1 mg/day bumetanide for 3 months (3). Effectiveness of bumetanide treatment has shown in a 3-month placebo-controlled double-blind randomized controlled trial (RCT) involving 60 children with ASD or Asperger syndrome in which autistic traits were evaluated by Childhood Autism Rating Scale (CARS), Clinical Global Impressions, Autism Diagnostic Observation Schedule and video films at day 0 and 90 (4). Further placebocontrolled RCTs revealed that administration of bumetanide treatment along with applied behavior analysis (ABA) is superior treatment option compared to ABA alone (5). Beneficial effects were also reported in few other RCTs involving 88 and 83 subjects with similar autistic behavior evaluation tools and case reports while most commonly observed adverse effects include hypokalemia, dehydration, loss of appetite and asthenia (6-8). Clinical trials investigating effectiveness of bumetanide in other neuropsychiatric disorders including neonatal seizures, schizophrenia and Parkinson diseases have been conducted (9, 10).