Popular drugs used in off-label prescriptions for chronic insomnia

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

Vaughn McCall, MD, MS, 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 was held in June in an effort to build consensus on a series of questions regarding chronic insomnia.

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

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

According to McCall, 78% 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,” he said.

Believing the widespread use of these drugs “suggests that there must be substantial evidence supporting this practice,” McCall searched the medical literature for all 10 drugs, looking for randomized controlled trials, particularly 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. And, while McCall uncovered two small short-term trials that showed use of trazodone was better than placebo for patients already on antidepressants, he found only a limited number of small studies to support use of four other drugs.

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

Possibly many of the approved hypnotic drugs, which are controlled substances, have firm limits on duration of use, forcing psychiatrists to find something else. Or, McCall offered, it may be due to “Erroneous beliefs on the part of providers that off-label medications have demonstrated sustained efficacy and are safer.”

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

SOURCE: Wake Forest University Baptist Medical Center Media Advisory, “Many Drugs Prescribed for Chronic Insomnia Are Not Approved for That Purpose,” June 14, 2005.