Long-term help for insomniacs: New generation of sleep aids

Over the next year, sleep experts predict the pharmacological treatment of insomnia will change significantly because of the approval of new agents not limited to short-term use as well as alterations to the formulations of older drugs.

"The old dogma of you can only use sleeping pills for four weeks is starting to be questioned," said Robert Vorona, MD, assistant professor in the division of sleep medicine at Eastern Virginia Medical School in Norfolk.

The first of the new generation of non-benzodiazepines, Lunesta (eszopiclone), was approved by the Food and Drug Administration in December 2004. Unlike its predecessors, this sleep drug is approved without the recommendation that use be limited to less than two weeks, and physicians are likely to hear a lot about it in the coming months.

Sepracor Inc., Lunesta's manufacturer, is expected to launch the medication this spring with a combined direct-to-consumer and direct-to-physician campaign budget of more than $60 million. Additionally, more than 1,200 drug representatives will be sent out to promote the drug to primary care physicians.

But this won't be happening in a vacuum. Physicians will also be hearing more about insomnia and insomnia medications in general because pharmaceutical business analysts expect this market sector to experience big changes in the next months and beyond.

"The insomnia marketplace will see vast expansion over the next decade," according to Decision Resources Inc., an international pharmaceutical consulting firm, in its insomnia report published in August.

Meanwhile, on the heels of the FDA's Lunesta approval, Sanofi-Synthelabo Inc. intends to apply for approval of its drug, Ambien (zolpidem tartrate) for long-term use. King Pharmaceuticals is expected to do the same for its drug Sonata (zaleplon). Both companies are developing extended-release versions. In addition, Neurocrine Biosciences in conjunction with Pfizer is expected to launch indiplon, which does not yet have a trade name, in both immediate release and extended-release formulations later this year.

Additionally, two medications currently in phase III trials could represent entirely new treatment approaches. Takeda Pharmaceuticals is developing TAK-375 (Ramelteon), a melatonin receptor agonist, and Merck & Co. and H. Lundbeck A/S are developing gaboxadol, a GABA-A agonist which has no trade name yet.

"New options for patients are always welcome," said Susan Esther, MD, a member of the board of directors of the American Academy of Sleep Medicine. "But in about a year or so we're going to have some novel new treatments, and that's going to be big."

Concern about masking conditions

While there is joy at additional options for patients who can't sleep, there is also concern that medications for longer-term use may mask some of the underlying conditions that cause the insomnia.

"Insomnia is really a symptom," said Gordon Walbroehl, MD, professor of family medicine at Wright State University School of Medicine in Dayton, Ohio. "It's not really a disease. I get worried if somebody gets dependent on sleep pills for six months or more that we might be missing something more significant like anxiety, depression or sleep apnea or something else."

These drugs may also overshadow behavioral interventions which tend to be more effective over time.

"It is easier to prescribe a pill than it is to tell a patient to adopt a regular bedtime and wake time, to avoid TV and reading in the bed, engage in regular exercise, cut down on caffeine intake, stop smoking and not drink [alcohol] to excess," said Dr. Vorona. "There's the potential that folks will say that it's more efficient to simply say, 'take this pill,' instead of engaging in these more time-intensive but, over the long haul, more efficacious behavioral interventions."

Meanwhile, there is new evidence that insomnia and obesity may have a causal link. A study published in the Jan. 10 Archives of Internal Medicine suggested that the two conditions may be closely interrelated. Researchers surveyed slightly more than 1,000 patients presenting to four primary care practices and found that those who were overweight or obese tended to sleep 16 minutes less than those who were normal weight.

"There are hormonal alterations that occur as a result of insufficient sleep," said Dr. Vorona, lead author on the study. "And those alterations in hormones might be putting you at increased risk for obesity."

Experts caution, though, that a cause-and-effect relationship has still not been proven, and it is still premature to treat obesity with extra sleep or a problem sleeping with weight-loss recommendations. Excess weight may be one of the underappreciated effects of a lack of sleep. A lack of sleep may be one of the ill effects of extra weight. Or they may feed on each other.

"Weight regulation is a complex problem, and there are many different factors at play," said Joseph Bass, MD, PhD, an endocrinologist and assistant professor of medicine at Northwestern University Feinberg School of Medicine in Evanston, Ill. who co-authored the accompanying Archives editorial. "One of them is behavior, and one of the behaviors is sleep."