Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies.
Bumetanide is ineffective for core ASD symptoms—do not pursue it as a treatment option.
01Research in Context
What this study did
Two teams ran large drug trials with kids and teens who have autism. They gave half the children bumetanide, a water-pill that was hoped to calm brain signals. The other half got plain liquid that looked the same.
Doctors checked every child with the CARS-2 scale and other tests to see if autism signs eased after months of daily doses.
What they found
The pill group scored the same as the placebo group on the CARS-2. No secondary measure moved either.
In short, bumetanide did nothing for core autism traits in these two big trials.
How this fits with other research
Lung et al. (2018) and Boudreau et al. (2015) also report null results. They found that children conceived by assisted reproductive technology do not have higher autism odds or worse symptoms. Together with Fuentes et al. (2023), the pattern is clear: several hoped-for fixes or risk factors simply do not change autism presentation.
Green et al. (2020) show another sobering outcome: school-age autistic children without intellectual disability still fall behind in math. A drug that fails core symptoms (Joaquin) leaves academic gaps untouched (C et al.).
Iadarola et al. (2018) offer a brighter note. Their classroom transition package STAT cut behavior problems even in under-resourced schools. The contrast is stark: a systems-level teaching move helped, while a brain-level pill did not.
Why it matters
You can stop wondering about bumetanide. The evidence is in, and it is negative. Spend your energy on classroom tools like STAT or on skill-building ABA programs that have data behind them. When families ask about new pills, show them this study and pivot to interventions you can deliver today.
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02At a glance
03Original abstract
The efficacy and safety of bumetanide oral solution for the treatment of autism spectrum disorder (ASD) in children and adolescents was evaluated in two international, multi-center, randomized, double-blind, placebo-controlled phase III trials; one enrolled patients aged 7-17 years (SIGN 1 trial) and the other enrolled younger patients aged 2-6 years (SIGN 2). In both studies, patients were randomized to receive bumetanide oral solution twice daily (BID) or placebo BID during a 6-month double-blind treatment period. The primary endpoint was change in Childhood Autism Rating Scale 2 (CARS2) total raw score from baseline to Week 26. Key secondary endpoints included changes in Social Responsiveness Scale-2, Clinical Global Impression Scale, and Vineland Adaptive Behavior Scale. Each study enrolled 211 patients (bumetanide, n = 107; placebo, n = 104). Both studies were terminated early due to absence of any significant difference between bumetanide and placebo in the overall studied populations. In both studies, CARS2 total raw score decreased from baseline to Week 26 in the bumetanide and placebo groups, with no statistically significant difference between groups. No differences were observed between treatment groups for any of the secondary efficacy endpoints in either study. In both studies, treatment-emergent adverse events that occurred more frequently with bumetanide than placebo included thirst, polyuria, hypokalemia, and dry mouth. These large phase III trials failed to demonstrate a benefit of bumetanide for the treatment of pediatric ASD compared with placebo. Consequently, the sponsor has discontinued the development of bumetanide for the treatment of this condition. Trial registration: https://clinicaltrials.gov: SIGN 1: NCT03715166; SIGN 2: NCT03715153.
Autism research : official journal of the International Society for Autism Research, 2023 · doi:10.1002/aur.3005