Low dose anti-anxiety drugs may treat autism

[DocM]

Can't wait to human trials.

http://www.scientificamerican.com/article/antianxiety-drugs-successfully-treat-autism/

Parents trying to help their children manage the constellation of symptoms associated with autism have had few drug options available to treat key aspects of the disorder. Now, encouraging results from a new study suggest that low doses of antianxiety medications already available on the market, such as benzodiazepines, might become the latest drugs parents ask doctors to prescribe, even if the drugs are not an approved treatment for autism.

 

A move to antianxiety medications would mark a dramatic shift in how physicians treat autism spectrum disorder. Currently, treatments for autism are usually prescribed off-label and focus on helping treat aggression or hyperactivity with medications including Ritalin and antipsychotic medications, not social behavioral symptoms. But the new findings, in mice, have already sparked conversations among physicians about how the drugs could be used to help autism patients.

 

Mice bred to have autismlike symptoms were injected with low doses of antianxiety drugs and showed notable behavioral shifts: improved social interaction, decreased repetitive behaviors and better spatial learning. Moreover, the low doses of the drug did not appear to cause lethargy, a common negative side effect of antianxiety medications. ?To me the significance of this is that it uses drugs that are safe, that we already know so much about. It?s a relatively simple?or conceptually simple?way to treat autism that seems to be effective,? says Todd Scheuer, co-author of the study and a research professor of pharmacology at the University of Washington.

 

Exactly how much impact the drugs could have on a given patient remains unknown, and no human clinical trials have yet been performed. Moreover, because autism spectrum disorder encompasses a vast array of symptoms and degrees of severity, it is unclear exactly what part of the spectrum the mice best represent. The findings are published in the March 19 issue of Neuron.

 

Benzodiazepines target certain receptors for the neurotransmitter GABA (gamma-aminobutyric acid), an inhibitory chemical that dampens specific brain-wave activity and is one of the most common neurotransmitters in the brain. Benzodiazepines act on GABA receptors, making them stay open longer and allowing more negative ions into the cell that can inhibit communication between the cells. Hence, GABA would have a bigger effect, boosting inhibition that would make excitatory neurons less active.

 

The findings add weight to the hypothesis that the signature behavioral features of autism are fueled by an imbalance between excitatory and inhibitory neurotransmission in the brain. With autism, the inhibition is believed to be a little less than normal, so the excitatory neurons can become overactive, resulting in autistic behaviors.

 

The findings also suggest there is only a small dosage window for the drugs to have the desired impact. Higher amounts of the drug clonazepam, the benzodiazepine used in the experiment, did not alleviate autism symptoms and carried the risk of leading to lethargy. The researchers are not sure why there was such a narrow range of effective dosing but hope future medications could be developed that would help patients without making them feel dopey. ?At higher doses, most drugs start having less specific effects. My sense is when you get the dose too high, you are flooding the system, and it?s binding to some of the receptors where you don?t want it to bind,? says Linmarie Sikich, director of the Adolescent and School-Age Psychiatric Intervention Research Program (ASPIRE) at the University of North Carolina at Chapel Hill, who was not involved in the research.

 

For this study the researchers targeted very specific types of GABA receptors to improve social behaviors with clonazepam, but the team also found that by using a different drug, they could target other GABA receptors and actually reduce the ability to socially interact in normal mice?underscoring that future medications would need to target very specific receptors so as not to diminish the drug?s impacts.

 

At much higher doses, benzodiazepines treat epilepsy and anxiety in human patients now, including those with autism. Still, Sikich cautions, the drugs may not be a good fit for everyone. Physicians considering prescribing lower doses of clonazepam for autism in the future would also have to weigh how these drugs may impact children and adults differently; benzodiazepines that make adults calmer and less agitated can have the opposite impact in young children, she says. But some clinicians are already eager to give the medication a go. ?I would feel comfortable trying this off-label in children,? says Wendy Moyal, assistant medical director of the New York?Presbyterian Hospital?s Center for Autism and the Developing Brain. ?Right now we have no medications treating the core symptoms of autism. This is a medication that has been around for a long time, and I know the effects and side effects, so I feel comfortable using this medication off-label. These findings are exciting,? she says.

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