Anesthesia Antidote May Help Treat Extreme Sleep Disorder

A disorder that causes extreme sleepiness may be better treated with a drug commonly used to counter the effects of a Valium overdose, researchers said.

Primary hypersomnia is linked to a substance that boosts the effects of gamma-aminobutyric acid, a neurotransmitter that limits excess brain activity and leads to the drowsiness, said David Rye, the lead author of a study published today in the journal Science Translational Medicine. Patients are usually prescribed stimulants, though they don’t work well, he said.

“We thought, maybe that’s not the way to think about it,” Rye, a neurology professor at Emory University School of Medicine in Atlanta, said in an interview. “Maybe the problem isn’t the accelerator needs to be pushed, maybe the problem is the parking brake needs to be disengaged.”

Instead of stimulants, researchers tried flumazenil, an antidote used to counter sedatives such as benzodiazepine, Valium and Ambien. Some of the study’s participants, who suffer from excessive sleepiness even after a full night’s rest, improved their reaction times after being given flumazenil to levels approaching a non-sleepy control group, according to the study. Attention lapses were reduced 85 percent.

“It’s a breakthrough,” said Rochelle Zak, a sleep medicine specialist at the University of California San Francisco Medical Center, in an interview. “It gives a mechanism for doing clinically relevant future studies, both in terms of understanding the mechanism and in terms of developing an effective therapy.”

Peptide Search

The patients, who slept 75 hours a week on average, exhibited reaction times similar to someone who has been awake for 24 hours, or a person with a blood alcohol level higher than the legal limit in many U.S. states, Rye said.

People with the disorder are typically diagnosed with narcolepsy, though they don’t have sleep attacks in the daytime like those with that diagnosis are prone to do, Rye said. The condition is so severe that four of the patients in the study applied for disability and four others had to take leaves of absence from work or school.

What the actual substance is that causes the effect on gamma-aminobutyric acid, or GABA, is unknown, Rye said. It’s likely a peptide, though more work needs to be done studying it. Also unknown is the disorder’s prevalence, according to the Diagnostic and Statistical Manual of Mental Disorders. Rye estimated it affects at least one in every 300 people.

Another problem: flumazenil, an intravenous drug, is hard to obtain in large doses and its effect on hypersomniacs seems to wear off within two hours, Rye said.

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