Is FDA “Waking Up” to Off-Label Use?

The U.S. Food & Drug Administration (FDA) recently denied Cephalon’s bid to use its alertness drug, Nuvigil, to treat jet lag. Nuvigil is a longer-lasting form of the drugmaker Cephalon’s top seller, Provigil, which raked in $1 billion in sales last year.

FDA denies off-label use of drugAccording to the New York Times, Provigil is expected to face generic competition in 2012, so Cephalon is “trying to shift as many patients as possible to the newer drug.” Both drugs are approved to treat the excessive sleepiness associated with narcolepsy, sleep apnea and shift work.

Note that Nuvigil is not designed to actually treat jet lag, in which the body’s internal clock is out of sync with the time in one’s location. It simply helps people stay awake. Of course, that’s not going to help half of the jet lag sufferers out there, who (due to traveling the “wrong” direction) are feeling alert when they should be sleeping. You can bet other pharmaceutical companies that make insomnia medications are working on an off-label jet lag application for their drugs.

On second thought, maybe not. You see, the most frequently used drugs for treating chronic insomnia have never been approved for that purpose by the 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 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 is 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 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. Further, he stated that evidence to support their effectiveness is poor.

McCall said that between 1987 and 1996 the use of FDA-approved sleep medications called “hypnotics” declined by 54 percent. Yet, during the same period, “the use of trazodone (Desyrel) and other sedating antidepressants rose by 146 percent. “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 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.

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

McCall 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. Meanwhile, McCall uncovered two small short-term trials that showed use of trazodone was better than placebo for patients already on antidepressants, but 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.

6 thoughts on “Is FDA “Waking Up” to Off-Label Use?”

  1. I agree that the public needs to be aware of what the drug companies are doing and the policy makers should be more concerned with the public’s welfare!

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