The Efficacy and Safety of Bumetanide in Children with Autism Spectrum Disorder: An Updated Meta-analysis

Abstract

Autism spectrum disorder (ASD) is a complex range of neurodevelopmental disorders. The treatment of ASD is challenging since there are no approved drugs except for risperidone and aripiprazole, which have a limited effect on core symptoms and are associated with a wide range of adverse events. Bumetanide is a loop diuretic suggested to play a role in ASD symptoms by modulating the GABAergic system. This meta-analysis aims to evaluate the efficacy and safety of bumetanide on ASD symptom management. We included randomized controlled trials comparing bumetanide with placebo or conventional treatment. Our primary outcomes included the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS-2), Clinical Global Impression- Efficacy Index (CGI-EI), Social interaction (SI), repetitive behavior and restricted interests (RRB), and adverse events. Bumetanide was associated with significant improvement in CARS total score (MD = -2.28; 95% CI = [-4.07, -0.49], p = 0.01) and CGI-EI (MD = 0.27; 95% CI = [0.09, 0.44], p = 0.003) compared to placebo. However, no significant difference was found in the SRS-2 score. Findings for SI and RRB were inconsistent depending on the pooled scales, with significant results observed when pooling SRS-2 but not when pooling ADOS. Bumetanide was generally safe and well-tolerated. Common adverse events include polyurea, hypokalemia, and dehydration. Although statistically significant improvements were observed on some measures, we cannot conclude the superiority of bumetanide in alleviating ASD symptoms. Further large clinical trials should be conducted to determine the effect of bumetanide on different symptoms of ASD and the variation in treatment effect among different patient populations.