Dalmane

When the U.S. National Institutes of Health convened a State-of-the-Science Conference on insomnia last June, it came down hard on the drugs most people use for this common affliction. The independent panel of experts chosen months before the conference had been given the task of assessing the supporting scientific evidence for the full range of treatments. It concluded that the drugs most often used to treat insomnia--antihistamines and antidepressants--have never been proven effective for this purpose. And though insomnia can persist for decades, the panel found that most prescription drugs approved for this condition have not been carefully evaluated for long-term use. The panel advised greater use of one non-drug approach to sleeplessness, a technique called cognitive-behavioral therapy.

Still, most insomniacs continue to turn to drugs in greater numbers. And the ubiquitous drug advertising campaigns encourage them to do so.

Ambien CR and Lunesta

Eight prescription drugs are approved by the Food and Drug Administration (FDA) for insomnia. Two of them have dominated recently in terms of advertising to the public. Ambien CR is a new extended-release version of Ambien, which has been on the market for 12 years. Ambien is so well known that full-page ads for its new extended-release version are appearing in magazines without mention of what the drug is for. The manufacturer, Sanofi-Aventis, is aggressively selling this new version to hold on to its market share as Ambien is due to go off patent next year. (Ambien was the world's most popular prescription sleep drug in 2004, accounting for $2.1 billion in sales.) The full-page ads announce a "Free 7-Day Trial Offer" for Ambien CR. An accompanying coupon falls out of the magazine that people are encouraged to bring to their doctors for a starter kit of free pills.

It's good to keep in mind when reading such ads that omitting the purpose of the drug allows the manufacturer to avoid identifying the harms associated with the drug and the warning that it is only for short-term use. One would have to read the packet insert, or what the FDA calls the label (for access, see page 3) to learn about adverse effects that include abnormal thinking, behavior changes, anxiety, memory loss, and addiction. Companies that make sleeping pills assert that these reactions can occur in a small number of people who take any drug in this class known as sedative/hypnotics. All drugs in this class are also known to cause what the manufacturers prefer to call "dependency," when taken for more than a few weeks.

Ambien CR purportedly has the advantage of keeping people asleep longer. Although short-term use is never spelled out, the packet insert indicates just how brief the FDA-required trials were. Only two trials were performed to demonstrate efficacy. Both were only three weeks in duration, and assessments were conducted after two weeks of treatment.

Lunesta, which came on the market last April, is the strongest rival to Ambien. So far, it is the only prescription sleep medication approved by the FDA for long-term use. Even so, its manufacturer, Sepracor, is explicit in the fine print of its magazine and newspaper ads, stating, "It [insomnia] usually requires treatment for only a short time, usually 7 to 10 days. If your insomnia does not improve after 7 to 10 days of treatment, see your doctor, because it may be a sign of an underlying condition."

The packet insert for Lunesta has this summary of clinical trial findings without quantifying how much sleep improvement people can expect from this drug: "Lunestra significantly improved sleep latency and improved measures of sleep maintenance (objectively measured as wake time after sleep onset and subjectively measured a total sleep time)." And here's a key warning that might be overlooked "Be aware that you may have more sleeping problems the first night or two after stopping any sleep medication."

Lunesta and Ambien CR pose the risk of a form of memory loss known as "traveler's amnesia." This can occur during an airplane flight when the person wakes up before the effect of the medicine is gone. The drug should be avoided in such a circumstance when it is impossible to get a full night of sleep. Both Lunesta and Ambien CR carry the warning not to drink alcohol. And both drugs should be taken in the smallest effective dose by people over age 65 years.

Short-Term Use of Prescription Sleep Drugs

Suppose you are one of those rare older people who uses sleep medicines appropriately--no more than ten days. What are the benefits and harms of short-term use? A team of Canadian researchers led by Jennifer Glass, PhD, University of Toronto, conducted an analysis of all studies in which people over the age of 60 years had been given one of the standard prescription drugs for insomnia, including Ativan, Xanax, Restoril, Dalmane, Ambien, and Sonata. Altogether, the analysis included 24 studies involving 2,417 participants who had taken either a placebo (sugar pill) or one of the above prescription drugs. To be included, the studies had to assess any of the above drugs taken for at least five consecutive nights for insomnia. Findings were published last month in the British medical journal, BMJ.

--The drugs were associated with harms that are particularly detrimental to older people, such as cognitive effects, falls, and ataxia (inability to coordinate the muscles in voluntary movement);

--adverse cognitive effects were five times more common in people on a drug than in those on the placebo;

--daytime fatigue was nearly three times more common in people taking a drug;

--and the drugs provided only marginal improvements.

Dr. Glass and colleagues concluded that the short-term benefits of these drugs may not justify the increased harm, especially to older people who are already at risk for adverse cognitive reactions.

Other Approaches to Sleeplessness

The panel of experts at the State-of-the-Science Conference identified antihistamines as the most commonly used over-the-counter treatment for insomnia. But there is no systematic evidence to demonstrate effectiveness and there are significant concerns about risks, according to the panel. The adverse effects include "residual daytime sedation, diminished cognitive function, and delirium, the latter being of particular concern to the elderly."

Alcohol does reduce the time it takes to fall asleep, but large amounts will result in poorer quality sleep and awakening during the night. Melatonin, a natural hormone that can be purchased over the counter, is better for jet lag than insomnia. Furthermore, there is no information about the safety of long-term use.

The panel also assessed alternatives to drugs, such as tai chi, yoga, acupuncture, and light therapy. All were deemed potentially useful, but inadequately evaluated. Only one non-pharmacological approach to sleeplessness, called cognitive-behavioral therapy (CBT), was judged to have been proven effective in moderate to high-quality trials that compared it to drug therapy. This form of therapy was shown to be as effective as prescription drugs are for short-term treatment of insomnia minus the risks.

CBT was described by the panel as "cognitive restructuring in which anxiety-producing beliefs and erroneous beliefs about sleep and sleep loss are specifically targeted." The treatment involves a series of visits to a therapist trained in this method, a prospect that might be out of reach for many people.

To explore a lower cost, self-help version of CBT that involves $35 and access to the Internet, go to www.myselfhelp.com, which describes itself as funded in part through a series of Small Business Innovative Research Grants from the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services.

How to Obtain the Packet Insert, aka Drug Label

The packet insert, also known as the drug label, is produced by the drug's manufacturer with FDA oversight. It is intended for the prescribing physician and is entirely different from the pharmacy-generated drug information. Only the packet insert has complete information on the drug, including what was proven in the FDA-required clinical trials. It is distinctive in its fine print and length (@20-40 pages), as opposed to the consumer friendly format of the usual pharmacy-generated drug information. The packet inserts of many drugs contain both a professional and a patient version. Read both.

There are several ways to obtain the packet insert. Ask the pharmacist for a copy when purchasing the drug; go to the public library and consult the Physicians' Desk Reference; visit the FDA's Web site (www.fda.gov) and click into the following sections: drugs, drugs@FDA, the drug's name, and finally, drug label. And sometimes this works best: perform a google search with the drug's name plus the word label.

COPYRIGHT 2005 Center for Medical Consumers, Inc.
COPYRIGHT 2005 Gale Group