APSS: Short-Wave Sleep Enhancers May Have Roll in Insomnia

MINNEAPOLIS, Minn., June 12 -- Despite disappointing performance in clinical trials, anti-insomnia drugs that improve short-wave sleep may still have a role in helping people get a good night's rest, a sleep specialist predicted here.

"We haven't heard the last of short-wave sleep," said James Walsh, Ph.D., of St. John's Mercy and St. Luke's Hospital, St. Louis, during an industry-sponsored satellite symposium held in conjunction with the Associated Professional Sleep Societies meeting.

The combination of drugs that increase short-wave sleep, such as tiagabine and gaboxadol, plus cognitive behavioral therapy and perhaps benzodiazepines, might be able to produce the results that help patients sleep, he said.

Dr. Walsh, one of four speakers who discussed treatments to improve sleep in insomnia patients, noted that studies with both the anticonvulsant tiagabine (Gabitril) and the experimental drug gaboxodol proved they could improve short-wave sleep, but failed to provide major relief to patients.

The studies might have been too short to have the needed impact, he said, and predicted that further attempts with these types of drugs would be forthcoming.

Neil Harrison, Ph.D., of Cornell University, opened the symposium with a review of the pharmacology of the key GABA-a receptor, noting the heterogeneity of the 19 distinct receptors and how various pharmaceutical agents involved in the treatment of insomnia fit into those receptors.

New experiments in an animal model of insomnia was the focus for Clifford Saper, M.D., Ph.D., of Harvard. The hope, he said, is that they may pinpoint where and how pharmaceuticals can reduce the arousal functions that prevent insomniacs from getting to sleep.

Creating lesion in the brains of rats -- "something I couldn't get our IRB to approve for humans," he joked -- Dr. Saper and Georgina Cano, Ph.D., determined that a key to insomnia may lie in the brain's amygdala.

The amygdala is important in processing emotion and in the acquisition and expression of fear and anxiety, Dr. Saper noted.

When normal people sleep, the major portions of the brain's cortex quiets but "the entire brain doesn't go to sleep with insomniacs," explained Eric Nofzinger, M.D., of the University of Pittsburgh, demonstrating how positron emission tomography and functional magnetic resonance imaging have enlightened research into how the brain operates in insomniacs compared with those who sleep well.

In insomniacs, the limbic system is activated, said Dr. Nofzinger, and suggested that drugs that could target that system might help sleep patterns of these patients.