3. James BJ, Gales MA, Gales BJ. Bumetanide for autism spectrum disorder in children: a review of randomized controlled trials. Ann Pharmacother. 2019;53(5):537-544.
The persistence of excitatory gamma-aminobutyric acid (GABA) signaling has been found in patients with ASD. Bumetanide is a sodium-potassium-chloride cotransporter 1 (NKCC1) antagonist that not only decreases intracellular chloride, but also aberrantly decreases GABA signaling. This potent loop diuretic is a proposed treatment for symptoms of ASD. James et al6 evaluated the safety and efficacy of bumetanide use in children with ASD.
Study design
- Researchers searched the PubMed and Ovid MEDLINE databases for the terms “autism” and “bumetanide” between 1946 and 2018. A total of 26 articles were screened by title, 7 were screened by full text, and 3 articles were included in the study. The remaining articles were excluded due to study design and use of non-human subjects.
- All 3 randomized controlled trials evaluated the effects of low-dose oral bumetanide (most common dose was 0.5 mg twice daily) in a total of 208 patients age 2 to 18 years.
- Measurement scales used in the 3 studies included the Childhood Autism Rating Scale (CARS), Clinical Global Impressions Scale (CGI), Autism Behavioral Checklist (ABC), Social Responsiveness Scale (SRS), and Autism Diagnostic Observation Schedule-Generic (ADOS-G).
Outcomes
- Bumetanide improved scores on multiple autism assessment scales, including CARS, but the degree of improvement was not consistent across the 3 trials.
- There was a statistically significant improvement in ASD symptoms as measured by CGI in all 3 trials, and statistically significant improvements on the ABC and SRS in 2 trials. No improvements were noted on the ADOS-G in any of the trials.
- No dose-effect correlation was identified, but hypokalemia and polyuria were more prevalent with higher doses of bumetanide.
Conclusion
- Low-dose oral bumetanide improved social communication, social interactions, and restricted interests in patients with moderate to severe ASD. However, the 3 trials used different evaluation methods and observed varying degrees of improvement, which makes it difficult to make recommendations for or against the use of bumetanide.
- Streamlined trials with a consensus on evaluation methodology are needed to draw conclusions about the efficacy and safety of bumetanide as a treatment for ASD.
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