A new sleep drug by Merck will affect a different part of the brain than a generation of older medicines which depresses brain activity with hopes for fewer side effects

Updated June 25, 2013, 5:21 a.m. ET

New Entry in the Quest for a Perfect Sleep Drug

By CHRISTOPHER WEAVER

A new sleep drug by Merck & Co. is expected to gain U.S. approval in the coming months, even as its main competitor is coming under growing scrutiny by regulators and doctors for sometimes-dangerous side effects. The new drug, known as suvorexant, will affect a different part of the brain than a generation of older medicines such as zolpidem, known as Ambien, which depresses brain activity. The hope is that suvorexant will cause fewer side effects than its older counterparts.

An estimated 25% or more Americans face a bout of insomnia in a given year, and at least 1 in 10 suffers the chronic form of the disorder, routinely facing sleepless nights, according to the Centers for Disease Control and Prevention.

“There’s a need for more drugs,” said Russell Rosenberg, chairman of the National Sleep Foundation. Current drugs don’t work for everyone, and a push to lower doses amid safety concerns has led to patients “coming in and saying it’s not working as well,” said Dr. Rosenberg, a practicing sleep psychologist and director of the Atlanta School of Sleep Medicine and Technology.

New sleep drugs may be facing a higher approval bar, amid rising concern that Ambien and similar drugs cause side effects such as risky bouts of sleepwalking and next-day drowsiness, which can impair driving. The U.S. Food and Drug Administration advised doctors to reduce doses of Ambien for women, and added new warnings to its labeling earlier this year.

FDA officials reviewing the new Merck drug are concerned that it is unsafe at higher doses and that it, too, can cause side effects including drowsiness that “can be severe and worsen suddenly,” the agency said in documents. A panel of FDA advisers recommended that lower doses receive approval, which is expected this summer, but the agency is not bound to such recommendations.

“Our philosophy is changing on sleep drugs,” said Ellis Unger, the FDA official overseeing drug approvals. Data showing the long-lingering effects of the medicines prompted the agency to push drug makers to conduct studies showing whether the drugs impair driving. It is also pushing companies to market drugs in lower doses, even if such doses aren’t effective for all patients, he said.

“We want to ask, does it help you sleep, does it help you stay asleep, and does it not ruin your next day?” Dr. Unger said.

That points to an intractable puzzle. Medicines to treat insomnia, which influence the chemistry of the brain, must strike a balance between effectively pushing patients into sleep, and limiting side effects that can turn a sleepless night into a more urgent health hazard for the patient—and bystanders. That balance has remained elusive.

With sleep drugs generally, “we like the effects in bed, but we don’t like it eight hours later,” said Thomas Roth, director of the Henry Ford Hospital’s sleep lab in Detroit, and a Merck consultant.

A string of recently developed drugs have failed to solve the problem. Rozerem, a melatonin-based drug meant to help induce sleep more naturally, just didn’t work well enough to catch on after it was introduced in 2005, doctors said. Silenor, a sleep aid approved in 2010, has also struggled. The company that makes it, Somaxon Inc., was acquired in March by another small drug maker.

Most widely used sleep drugs, including Ambien and its relatives, are so-called GABA receptor agonists, which work by stimulating chemicals that can cause sedation. Besides modern sleep aids, this class of drugs also includes ethanol—the alcohol in beer, wine and liquor—and the partially retired class of addictive sedative drugs called barbiturates. All act by slowing the brain, and most come with an unfortunate slew of next-day side effects including “hangovers.”

Yvonne Oby, 60, an office manager at a Chicago law firm, was taking Ambien for a bout of insomnia last year, but even with the medicine, she would wake in the middle of the night and fail to get back to sleep. The effects of the drug could follow her into the office, where she described arriving feeling “punch drunk.”

In late October last year, she stopped using the drug. She had been driving north on Lake Shore Drive, a highway skirting Lake Michigan, when she became anxious and dizzy behind the wheel. “I was crying and praying to find an exit” from the highway, she says. Ms. Oby has since begun receiving specialized cognitive-behavioral therapy at Northwestern Medicine, a Chicago health system. Such therapy may include relaxation methods to combat anxiety tied to insomnia, stimulus controls such as blackout shades and other measures.

Unlike Ambien, suvorexant interferes with the activity of a brain chemical some researchers call orexin, which causes alertness. In theory, doctors and researchers say, that mechanism would trigger fewer drowsiness-related side effects, and potentially more natural sleep, because it doesn’t depress brain activity in the same way as older drugs.

“This is the glue that enables us to stitch together the small bouts of wakefulness” into a full day of activity, said Thomas Kilduff, a researcher at SRI International, a Palo Alto, Calif.-based nonprofit research institute. Dr. Kilduff helped discover orexins, which his research team dubbed hypocretins.

Whether suvorexant delivers safer, more refreshing sleep could take years to determine. Problems with earlier drugs have been identified only when those medicines reached broad populations. Merck said it believes the drug will be an important option for insomnia patients.

Concerns about the side effects of older medicines have often accompanied the arrival of new sleep drugs. Some researchers note that Ambien in its early commercial life was considered the cure for troubling side effects associated with its predecessor, a drug called Halcion. In turn, Halcion and earlier benzodiazepine drugs replaced barbiturates, which caused side effects such as sometimes-fatal overdoses.