The most frequently used drugs for treating chronic insomnia have never been approved for that purpose by the U.S. Food
and Drug Administration (FDA), according to a sleep expert from Wake Forest University Baptist Medical Center.

Vaughn McCall, M.D., M.S., professor and chairman of the Department of Psychiatry and Behavioral Medicine, told a special
consensus panel at the National Institutes of Health (NIH) that he could find no evidence that randomized controlled clinical
trials had ever been conducted for five of the 10 pharmaceuticals prescribed most often for chronic insomnia.

None of the 10 are currently approved for insomnia, though all are FDA-approved as antidepressants, antipsychotics or
sedatives, he said.

The NIH State-of-the-Science Conference on Manifestations and Management of Chronic Insomnia in Adults, sponsored by the
National Institute of Mental Health and Office of Medical Applications Research, will continue through Wednesday, seeking to
build consensus on a series of questions on chronic insomnia.

“There is widespread use of off-label prescribed medications for insomnia,” said McCall, who directs the sleep laboratory at
Wake Forest Baptist. But he said that evidence to support their effectiveness is poor.

He said that during the 1990s, the use of FDA-approved sleep medications called hypnotics declined by 54 percent between 1987
and 1996, “while the use of trazodone (Desyrel) and other sedating antidepressants rose by 146 percent. This trend continued
through 2002, such that trazodone became the most frequently used medication for the treatment of insomnia.”

He said that 78 percent of psychiatrists now make trazodone their first choice.

“In addition to trazodone, a wide variety of antidepressants, antipsychotics and sedatives gained favor for the treatment of
insomnia despite the fact that none of these medications are approved for the treatment of insomnia.”

McCall said the widespread use of these drugs “suggests that there must be substantial evidence supporting this practice.”

So he searched the medical literature for all 10 drugs, looking for randomized controlled trials, especially those in which
the drug being tested was compared to an inert placebo.

He said he found one study that showed that trazodone was superior to placebo in the first week of treatment for insomnia,
but no better than placebo in the second week. For patients already on antidepressants, he found two small short-term trials
that showed use of trazodone was better than placebo.

He found a limited number of small studies to support use of four other drugs.

“Why are they used so often?” he asked.

One possible reason was that many of the approved hypnotic drugs, which are controlled substances, have firm limits on
duration of use, forcing psychiatrists to find something else.

Secondly, “Erroneous beliefs on the part of providers that off-label medications have demonstrated sustained efficacy and are
safer,” he said.

He told the panel, “Full scale, placebo-controlled clinical trials of some off-label medications are warranted in the
treatment of insomnia.”

Media Contacts: Robert Conn, rconnwfubmc.edu, Shannon Koontz, shkoontzwfubmc.edu, or Karen Richardson, krchrdsnwfubmc.edu,
at 336-716-4587.

About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North
Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. The
system comprises 1,298 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of
“America’s Best Hospitals” by U.S. News & World Report.

Contact: Robert Conn
rconnwfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
wfubmc.edu