Bumetanide for autism spectrum disorders: A systematic review and meta-analysis

ABSTRACT

Background: Autism spectrum disorders (ASD) is diagnosed primarily by the presence of impaired social interaction, social communication, and stereotypical behaviors. Bumetanide, a loop diuretic which acts by inhibiting Na+-K+-2Cl co-transporters (NKCC) NKCC1 and NKCC2 are explored as a pharmacological agent for treatment of ASD. Aim and Objectives: The aim of the study was to analyze safety and efficacy of bumetanide in treatment of ASD. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Autism” AND “Bumetanide.” Randomized or cross-over trials comparing efficacy of bumetanide versus placebo in ASD patients of any age group were included in analysis. Quantity of reduction in total Childhood Autism Rating Scale (CARS) score after 90 days of treatment with bumetanide was the primary outcome measure analyzed. Efficacy outcome measures were estimated by calculating the Mean Difference (MD) values and their 95% Confidence Intervals (CI) by both fixed and random effect models using Revman 5.4.1 software. Results: A total of six trials were found to be eligible and included in quantitative synthesis of efficacy. Small but significant decrease in total CARS score (MD ?1.86, 95% CI ?3.20, ?0.15, n = 352) and total social responsive scale score (MD ?9.38, 95% CI ?16.45, ?2.31, n = 171) on day 91 was evident in bumetanide treated group. Conclusions: Bumetanide appears to provide small but significant benefits in relieving ASD symptoms. These benefits are lesser in Chinese patients compared to European patients.