Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders.
Transl Psychiatry
; 7(3): e1056, 2017 03 14.
Article
em En
| MEDLINE
| ID: mdl-28291262
ABSTRACT
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl-)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2-18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P 0.0043) and the SRS score by more than 10 points (P 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bumetanida
/
Inibidores de Simportadores de Cloreto de Sódio e Potássio
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Transtorno do Espectro Autista
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França