Efficacy and Safety of Bumetanide in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by social and behavioural impairments. While behavioural therapies have progressed, pharmacological options for core symptoms remain inadequate. Bumetanide, an NKCC1 antagonist, has shown potential benefits in ASD. This systematic review and meta-analysis evaluated its efficacy and safety in children and adolescents.

We searched PubMed, ScienceDirect, Scopus, and ClinicalTrials.gov until April 2024 for RCTs and observational studies involving patients with ASD aged ≤18 years. Primary outcome measures the CARS, while secondary measures include the SRS, RBS, CGI-E, and safety profiles. We conducted separate analyses for RCTs and observational studies. Risk of bias was assessed using Cochrane RoB 2.0 for RCTs and ROBINS-I for observational studies.

Nine studies (7 RCTs, 2 observational), comprising 952 children and adolescents aged 3-18 years, were included. At 3 months, pooled analysis of randomized trials showed a significant reduction in CARS scores with bumetanide compared with placebo (WMD = -3.11; 95% CI = -6.11 to - 0.11; p = 0.04), though heterogeneity was high (I² = 92%). At 6 months, no significant difference was observed. Bumetanide increased the risks of hypokalaemia, polyuria, diuresis, and dehydration. The overall certainty of evidence was low to very low for most outcomes.

Although bumetanide shows short-term benefits on core ASD symptoms, high heterogeneity, limited durability, and safety issues constrain its clinical applicability.

Bumetanide may offer transient symptom improvement in ASD, but further highquality trials are warranted to establish long-term efficacy, safety, and responder profiles.