A randomised controlled trial of bumetanide in the treatment of autism in children.
A randomised controlled trial of bumetanide in the treatment of autism in children.
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DOI：
10.1038/tp.2012.124
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发表时间：
2012-12-11
影响因子：
6.8
通讯作者：
Ben-Ari Y
中科院分区：
文献类型：
--
作者：
Lemonnier E;Degrez C;Phelep M;Tyzio R;Josse F;Grandgeorge M;Hadjikhani N;Ben-Ari Y
在自闭症中，伽马氨基丁酸(GABA)介导的突触及其协调的振荡会发生改变。GABA作用的苯二氮卓类药物在一些自闭症患者中发挥矛盾的作用，增加了GABA像癫痫患者一样，由于细胞内氯浓度升高而兴奋神经元的可能性。在一项成功的先导性研究之后，我们现在进行了一项双盲临床试验，使用利尿剂、氯离子进口拮抗剂布美他尼来减少细胞内氯离子加强GABA能抑制。6 0例自闭症或阿斯伯格综合征患儿(3~11岁)接受3个月的安慰剂或布美他尼(每天1 mg)治疗，然后1个月冲洗。自闭症的严重程度是由盲目的独立评估者在第0天(D0)和第90天用录像片确定的。布美他尼显著降低了儿童自闭症评定量表(CARS)(D90−D0；P<；0.004治疗与安慰剂相比)、临床总体印象(P<；0.017治疗与安慰剂相比)和自闭症诊断观察计划值，当最严重的病例(CARS值高于平均值±S.D.；n=9)被剔除时(Wilcoxon检验：P值=0.031；学生t检验：P值=0.017)。副作用仅限于偶尔出现轻度低钾血症(3.0-3.5 mm L−1 K+)，并辅以补钾治疗。在一项配套研究中，慢性布美塔尼治疗显著提高了面部情绪标记的准确性，并增加了涉及社会和情绪感知的区域的大脑激活(Hadjikhani等人，提交)。因此，布美他尼是一种很有前途的治疗自闭症的新型药物。为了更好地确定最适合这种治疗的人群，有必要进行更大规模的试验。
Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study, we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3–11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90−D0; P<0.004 treated vs placebo), Clinical Global Impressions (P<0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean±s.d.; n=9) were removed (Wilcoxon test: P-value=0.031; Student's t-test: P-value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0–3.5 mM l−1 K+) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al., submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.
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DOI：
10.1152/physiologyonline.2000.15.6.309
发表时间：
2000-12-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Delpire, E
通讯作者：
Delpire, E
影响因子：
--
作者：
Croen, Lisa A.;Grether, Judith K.;Hendrick, Victoria
通讯作者：
Hendrick, Victoria
影响因子：
16.2
作者：
Chubykin, Alexander A.;Atasoy, Deniz;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
82.9
作者：
Dzhala, VI;Talos, DM;Staley, KJ
通讯作者：
Staley, KJ