Objective: To evaluate clinical trials using bumetanide in autism spectrum disorder (ASD) treatment.
Data sources: PubMed and Ovid MEDLINE (1946 to October 2018) were searched using terms bumetanide and autism. Bibliographies were reviewed for other relevant trials.
Study selection and data extraction: English language, randomized, controlled, clinical trials in humans were evaluated. Three trials met all inclusion criteria.
Data synthesis: Oral bumetanide was studied in 208 patients, 2 to 18 years old, with ASD. Trials evaluated bumetanide's impact on core behavioral features using several different autism assessment scales. All trials used the Childhood Autism Rating Scale to assess improvement at 90 days, with one trial finding statistical significance. The Clinical Global Impressions Scale identified statistically significant improvements in 2 of the 3 trials. The Autism Behavioral Checklist and Social Responsiveness Scales identified statistical benefit in the 2 trials utilizing those outcomes. Behaviors most improved by bumetanide included social communication, interactions, and restricted interest. No dose-effect correlation was identified in the dose-ranging trial. Adverse effects, including hypokalemia and polyuria, occurred more often with higher doses and resulted in withdrawal rates of 17% to 43%. Bumetanide 0.5 mg twice daily was the most studied and best tolerated dose. Limitations included unclear clinical success definitions and evaluation methodology variability. Relevance to Patient Care and Clinical Practice: No effective treatment options for core ASD symptoms have been approved. This review presents preliminary safety and efficacy data for bumetanide in ASD.
Conclusions: Low-dose oral bumetanide may be useful in patients with moderate to severe ASD when behavioral therapies are not available.
Keywords: autism; autism spectrum disorder; bumetanide; pediatrics.