Medical Mystery: Body's Own 'Valium' Leads to Extreme Sleepiness

PHOTO: Anna Sumner battled a disorder which caused her to experience intense drowsiness.Courtesy Anna Sumner
Anna Sumner battled a disorder which caused her to experience intense drowsiness.

For Anna Sumner, sleep was like a drug.

In 2007, Sumner -- then 32 -- had already battled chronic drowsiness for nearly a decade. What had manifested as bouts of sleepiness beginning in 1998 had gradually worsened over the years.

"I would awaken at 5 o'clock, and be unsure if it was 5 a.m., 5 p.m., or 5 a.m. the following day," Sumner said.

Eventually she sought treatment, but the stimulants doctors prescribed to help her stay awake also made her jumpy and raised her blood pressure. Doctors took her off the medications, and her fatigue returned worse than ever, eventually forcing her to take a leave of absence from work from her high-powered job as a lawyer.

When her condition progressed to the point that she was sleeping 16 to 18 hours per day, she knew she needed help.

"By the time I sought help at Emory, I craved sleep," she recalled. "I would get this feeling that if I didn't sleep right then, I simply wouldn't survive."

Sumner's case had puzzled doctors, who had ruled out common causes of fatigue. She wasn't anemic, and her thyroid was normal. Multiple sleep studies also showed that there was nothing unusual about her breathing at night.

That was before Dr. David Rye, a neurologist and sleep specialist at Emory University in Atlanta, tried a different approach. He performed a spinal tap on her, and he and his team studied the properties of her spinal fluid.

What they found was that Sumner's spinal fluid had similar properties to the sleeping pills such as diazepam -- commonly known as Valium.

The surprising findings of this rare case, and 31 other similar cases documented since, were published Wednesday in the journal Science Translational Medicine.

"Our study shows that a subgroup of sleepy people are making substances that mimic the actions of common sedatives," Rye said.

Medicines such as Valium, Ativan and Xanax belong to a class of medicines called benzodiazepines, which are used to bring on sleep and reduce anxiety, as well as to prepare people for surgery. Patients who overdose on benzodiazepines, or who need their anesthesia rapidly reversed are treated with an antidote medicine called flumazenil.

Testing their theory that Anna's body was making its own Valium-like substance, Rye's team admitted her to the hospital in June of 2007, placed an IV in her arm, and started a drip of the antidote.

"When they gave me flumazenil, I felt as if my eyelids opened up all the way," recounts Sumner. "I thought to myself, 'So this is what normal feels like.'"

The only problem was that flumazenil was only available intravenously. No one outside of a hospital ever needed the medicine before.

"Reformulating a medicine is not a simple process," Rye said, adding that flumazenil still is not available in a form that can be taken by mouth.

Fortunately, Anna had a medical-legal background, and was able obtain a "compassionate use exemption" from the Food and Drug Administration.

"It was as if I was enrolled in a clinical trial of one patient -- me," she said.

Roche Pharmaceuticals, the original makers of flumazenil, donated their remaining supply of the medicine to Anna in 2008. The drug had just gone off of patent, and other companies were about to start manufacturing it generically.

"My parents received the shipment, and took it to an apothecary in Atlanta," Sumner said. "They made it into pills for me."

Holding the pills under her tongue leads to almost immediate relief of her symptoms. "The pills taste terrible," she said. "But it's better than a port in my vein."

Interestingly, Sumner's condition may not be as rare as currently thought. Rye and his colleagues tested flumazenil on seven of the patients in their study, and found that it helped them all to some extent.

"It may be time to reclassify the sleep disorders," Rye said, noting that future study could include an assessment of the fraction of people who have similar sleep-causing substances in their spinal fluid. "The problem is that we do not yet have a rapid, accurate test for it."

Rye's lab continues to study this group of sleeping disorders, and hopes that a method of mass-producing flumazenil pills or creams may be developed. They suspect that these sleeping disorders may be far more common than currently thought.

"Flumazenil pills under the tongue worked for one patient," Rye said. "There is no reason to think that it couldn't help 10,000 needy patients.

"It is a life-changing treatment," Sumner said. "I want everyone with this disorder to feel the way I do."