Diuretic a Promising Treatment for Autism

Megan Brooks

January 30, 2020

The loop diuretic bumetanide appears to improve some of the core behavioral symptoms of autism by decreasing levels of the neurotransmitters gamma-aminobutyric acid (GABA), new research suggests.

Investigators found young children with autism spectrum disorder (ASD) treated with the diuretic for 3 months scored better on a behavior scale that measures emotional response as well as verbal and nonverbal communication compared with children taking a placebo.

"This study is important and exciting because it means that there is a drug that can improve social learning and reduce ASD symptoms during the time when the brains of these children are still developing," study investigator Barbara Sahakian, DSc, FMedSci, professor of clinical neuropsychology, University of Cambridge, United Kingdom, said in a news release.

The study was published online January 27 in Translational Psychiatry.

Mechanism Revealed

As reported by Medscape Medical News back in 2017, bumetanide has been shown in earlier research to improve ASD symptoms. However, the new study sheds light on the mechanism of the drug, which alters the ratio of GABA to glutamate in the brain.

"This is the first demonstration that bumetanide improves brain function and reduces symptoms by reducing the amount of the brain chemical GABA. Understanding this mechanism is a major step toward developing new and more effective drug treatments," study coinvestigator Ching-Po Lin, PhD, of National Yang-Ming University, Taipei, Taiwan, said in the release.

The study included 83 children aged 3 to 6 years with moderate to severe autism; 42 were treated with 0.5 mg of bumetanide twice a day for 3 months and 41 in the control group received no treatment. At baseline, both groups had similar scores on the Childhood Autism Rating Scale (CARS).

Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score of 3 or higher. The improvement in clinical symptoms was confirmed by the overall impression of a physician who was blinded to the study group.

Particularly noteworthy were decreases in repetitive behavior and decreased interest in objects in children taking bumetanide.

Fei Li, PhD, clinical lead on the study from Jiao Tong University School of Medicine in Shanghai, China, shared one interaction with a parent.

"The mother of a 4-year-old boy living in a rural area outside Shanghai who received the treatment told me that he was now better at making eye contact with family members and relatives and was able to participate more in activities," said Li in the news release. "In the future, we hope to be able to ensure all families, regardless of where they are living, can receive treatment for their child."

Neuroimaging studies showed that 3 months of treatment with bumetanide was associated with a decrease in the ratio of GABA to glutamate in two key brain regions: the insular cortex, which plays a role empathy and self-awareness, and the visual cortex, which is responsible for integrating and processing visual information. This decreased GABA/glutamate ratio was associated with a reduction in symptom severity.

"Not a Cure-All"

"Because social interaction and communication starts so early in life, it is best to use bumetanide as soon as possible after diagnosis," Sahakian told Medscape Medical News. "This gives the best possible chance for children with ASD to develop eye contact, smiling, and other forms of social communication, and to have a good quality of life and well-being," she added.

However, she noted that further studies are needed. If results of a large-scale, double-blind, placebo-controlled clinical trial "replicate the results of our study and find that bumetanide is safe and effective in reducing symptoms in children with moderate and severe ASD, then it will provide a treatment," but that is "probably 3 to 5 years away," she said.

Commenting on the findings for Medscape Medical News, Randi Hagerman, MD, medical director of the UC Davis MIND Institute in Sacramento, California, is not surprised by the positive results, having seen the benefits first-hand.

Hagerman, who was not involved in the research, said she tried bumetanide in a nonverbal patient with ASD who did "marvellously well" and was subsequently able to talk.

"I think it could be very helpful for individuals with autism. I don't think it's a cure-all, but I think this is one of the few medications that will show efficacy and make a difference. Because it's a diuretic, potassium levels must be followed closely," said Hagerman.

Hagerman added that her group at the MIND Institute will soon be starting a study of bumetanide in young children.

The study was supported by the Shanghai Municipal Commission of Health and Family Planning, Shanghai Shenkang Hospital Development Center, Shanghai Municipal Education Commission, National Natural Science Foundation of China, Shanghai Committee of Science and Technology, Xinhua Hospital of Shanghai Jiao Tong University School of Medicine, National Human Genetic Resources Sharing Service Platform, the National Key Research and Development Program of China, 111 Project, the Shanghai Municipal Science and Technology Major Project, Guangdong Key Project, and ZJ Lab. The authors and Hagerman have no relevant disclosures.

Transl Psychiatry. Published online January 27, 2020. Full text

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