Old Drug May Find New Use as Autism Treatment

A repurposed old drug known as bumetanide reduced key symptoms in children with an autism spectrum disorder, a group of French researchers reported in a study published online December 11, 2012, in Translational Psychiatry.

Bumetanide is a loop diuretic commonly prescribed for fluid retention caused by heart failure or liver or kidney disease. In the brain, however, it also acts on a transporter protein embedded in cell membrane to allow the outflow of intracellular chloride ion, thus lowering the concentration of chloride inside the cell.

Based on research into pediatric seizures, scientists believe that reducing intracellular chloride is important for GABA neurons’ inhibitory function in the brain. Therefore, bumetanide is being tested for the treatment of neonatal epilepsy as well as autism.

In the French study, Professor Eric Lemonnier, a clinician at CHRU Brest Hospital in Bohars, France, and colleagues carried out a randomized, double-blind, placebo-controlled study in 60 patients aged 3 to 11 who had been diagnosed with autism or Asperger’s syndrome. Half of these children took placebo and half took 1 mg of bumetanide every day for three months. They were evaluated for autism symptoms by clinicians who did not know which treatment each patient had received.

At the end of the three-month treatment period, children who took bumetanide showed an average reduction of 5.6 points on the Childhood Autism Rating Scale (CARS), which was a statistically significant change when compared with an average reduction of 1.8 points among the children who took placebo.

The CARS is a scale used to measure behavioral symptoms in autism spectrum disorders, and the assessments are usually made from a videotaped session of children playing and interacting with their caregiver and from directly questioning the children’s parents.

The participating clinicians also rated their overall impression of the patients’ change in autistic symptoms. Fourteen of the 30 bumetanide-treated patients were rated as having had either significant or small improvement, compared with six of the placebo-treated patients.

After digging more deeply into the data, the researchers concluded that among the five CARS subscales (designated A-E), the mean score in stereotyped behavior and restricted interest (subscale D) showed the largest difference between subjects who took bumetanide and those who took placebo. In addition, study patients with milder autism at baseline had a larger response to bumetanide than did those with more severe symptoms.

The safety of bumetanide is well known, since the drug has been widely used for decades. Because of its risk for causing hypokalemia, the researchers closely monitored the patients’ serum potassium levels and provided potassium supplements to six bumetanide-treated children whose potassium level dropped to or below 3.5 mMol/L. One child was withdrawn from the study early because of hypokalemia.

The researchers emphasized that bumetanide does not cure autism, as the patients’ severity of symptoms, measured by the CARS, went back up within one month after the end of study treatment. They also pointed out that larger clinical trials are needed to determine the right dosage of bumetanide and the types of patients most likely to benefit from this treatment. ■