Bumetanide 500microgram / Potassium chloride 573mg (potassium 7.7mmol) modified-release tablets

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.

Abstract licence: CC BY

The aim of this study was to establish whether bumetanide can abort an acute attack of weakness in patients with HypoPP. This was a randomised, double-blind, cross-over, placebo-controlled phase II clinical trial. Focal attack of weakness was induced by isometric exercise of ADM followed by rest (McManis protocol). Participants had two study visits and received either placebo or 2 mg bumetanide at attack onset (defined as 40 % decrement in the abductor digiti minimi CMAP amplitude from peak). CMAP measurements assessed attack severity and duration. Nine participants completed both visits. CMAP percentage of peak amplitudes in the bumetanide (40.6 %) versus placebo (34.9 %) group at 1hr following treatment did not differ significantly (estimated effect difference 5.9 % (95 % CI: (-5.7 %; 17.5 %), p = 0.27, primary outcome). CMAP amplitudes assessed by the area under the curve for early (0-2hr post-treatment) and late (2-4 h post-treatment) efficacy were not statistically different between bumetanide and placebo (early effect estimate 0.043, p = 0.3; late effect estimate 0.085, p = 0.1). Two participants recovered from the attack following bumetanide intake; none recovered following placebo. Bumetanide was well tolerated but not efficacious to rescue a focal attack in an immobilised hand in the majority of patients, although data supports further studies of this agent.

Abstract licence: CC BY