The Truth About Sleeping Pills

Not all sleep aids are the same. Here’s what science has to say about the effectiveness—and safety—of the many options out there

BY MAIA SZALAVITZ

EVERYONE SUFFERS THE OCCASIONAL sleepless night, but when a few restless evenings become weeks or months of insomnia, craving for sleep can become greater than for any food or drug—and the latter is what many of us turn to. A record number of Americans turn to sleeping pills at least once each month; 60 million prescriptions are written per year. But are these medications safe? How addictive are they? And which ones really work best and have the fewest side effects?

ELUSIVE The search for a good night’s sleep is a struggle for many, but these days there are more options than in the past.

These questions have become all the more complicated by research suggesting that most of the currently approved drugs are linked to increased risk for Alzheimer’s disease and dementia. On the other hand, so is sleep loss itself. Insomniacs face risk every way they turn, and the solutions are not straightforward—but there is hope.

Experts agree that natural sleep is the best sleep, but many think sleeping pills have a place for some people, for limited lengths of time.

“There’s no doubt that healthy sleep of adequate duration that is appropriately timed to the light and dark cycle and occurs without the presence of sleep illness is crucial to human health,” says Nathaniel Watson, a professor of neurology at the University of Washington in Seattle and director of the University’s Medicine Sleep Center. Sleep affects every aspect of well-being. “Cardiovascular functioning, metabolic health, mental health,” he says.“We spend one third of our life doing it, so it’s obviously going to be important to every disease known to mankind.”

That’s why, when insomnia occurs, early diagnosis and treatment are critical, say experts. It may help prevent a short-term issue from becoming a chronic problem—and one that needs serious interventions in the form of pharmaceutical or over-the-counter drugs.

“The wrong approach is to automatically give medication and think you’ve accomplished something,” says Timothy Morgenthaler, the president of the American Academy of Sleep Medicine and a professor of medicine at the Mayo Clinic. “It may be harmful. You need to take a good history and evaluate the patient to determine the cause,” he adds.

First, says Morgenthaler, conditions like depression and sleep apnea need to be ruled out. Both are common in the U.S., with depression affecting around 9% and sleep apnea affecting about 4% of the population. Sleeping pills alone can’t treat depression, although they may sometimes be prescribed for a short time in addition to other treatments. Other promising research shows that a kind of talk therapy—called cognitive behavioral therapy for insomnia (CBT-I)—can dramatically improve rates of full recovery from depression and sleeplessness. And because people with depression are at higher risk of addiction, experts caution it’s especially important to make sure the sleep issue is “primary insomnia” and not part of depression or another mental illness. Most mental illnesses, in fact, are accompanied by sleep disturbances, and research shows that some sleep issues can be eliminated with proper treatment of the underlying illness.

Sleep apnea, which is thought to be massively underdiagnosed, involves sleep interruption due to repeated brief cessations of breathing—and it can’t be treated with sleeping pills. The oxygen loss and sleep deprivation that come along with it increase risk for high blood pressure, heart disease, stroke and metabolic problems—and sleeping pills don’t address the respiratory difficulties that underlie it, so they can’t help.

But if primary insomnia is diagnosed, there are many different types of medication for it, including one that came onto the market just this year. They have varied advantages—and disadvantages. Here’s what you need to know.

THE NEWCOMER: BELSOMRA

The Food and Drug Administration recently approved a new drug called Belsomra (suvorexant), and it works in an entirely different way from previous medications. It was inspired by research on narcolepsy, a condition whose primary symptom is suddenly falling asleep at inappropriate times. People with narcolepsy have lost neurons containing a neurotransmitter called orexin, and this affects their ability to stay awake. This prompted scientists to wonder if blocking the action of this chemical at the right time might in fact help people sleep.

It does. “We’re hopeful that it’s going to really provide a new and, in many cases, more helpful alternative to what’s currently available,” says David Michelson, the vice president of neurosciences at Merck Research, a division of the company that makes the drug.

SLEEP SOLUTIONS Approximately 4% of Americans take prescription pills to help them make it through the night. Many more depend on over-the-counter medicines, while others endure their sleeplesness.

While it is a controlled substance, Belsomra does not seem to directly affect reward pathways in the brain the way many sleep medications do, which could mean that it has less potential for misuse. “It helps you fall asleep and also keeps you asleep,” Michelson says, noting that studies of people who have taken it for up to a year do not show that they suffer withdrawal symptoms or worse insomnia than they had previously when they stop. The most common side effect is sleepiness the next day, which, as with all sleeping pills, can impair driving.

“It’s an exciting development to have drugs with a novel mechanism of action,” says University of Washington sleep expert Watson.

But Michael Perlis, director of the behavioral sleep medicine program at the University of Pennsylvania’s Perelman School of Medicine, notes that with new drugs, many risks are unknown. “Large-scale, longitudinal comparative studies are needed to assess whether it has superior efficacy, durability and safety,” he says.

PROS It may work when other drugs have failed; seems to have less risk of misuse or dependence.

CONS It’s still new, which means that long-term risks are unknown.

THE OLD STANDBYS: OVER-THE-COUNTER ANTIHISTAMINES

When people suffer insomnia, the first drugs they turn to aren’t always the best. Over-the-counter drugs like Unisom, Benadryl and Sominex contain antihistamine medicines like diphenhydramine or doxylamine succinate, which were approved by the FDA for treating sneezing and allergies—but not for inducing sleep. The drugs, do, however, make people sleepy. Since they were approved by the FDA at a time when the restrictions were different, there is little data on their long-term safety and efficacy, even though consumers typically assume they are safer than prescription drugs.

The long-term risks are “unknown,” says Perlis, adding that “nothing” is known about how effective they are. Moreover, these drugs fall into a class of medications known as anticholinergics, which are associated with confusion in the elderly and increased risk for dementia.

It’s unclear whether they actually cause or hasten dementia, however, or whether conditions that these medications are used to treat—such as insomnia and allergies—are themselves responsible for the elevated risk. But studies show that the more anticholinergics a person takes, the greater the odds of dementia.

“You can also get dizziness and urinary retention,” says Watson. “When a patient comes to me [who has been using them], I typically move to a more traditional sleeping pill.”

OTC antihistamines do have one clear advantage besides convenience, however: they are not linked with withdrawal symptoms upon cessation, and they don’t appear to cause addictive behavior.

PROS They’re easy to get hold of.

CONS There’s not sufficient data on their long-term safety, and experts have noted correlations between their use and dementia.

THE “MOTHER’S LITTLE HELPERS”: BENZODIAZEPINES

Benzodiazepines are some of the most widely used prescription sleep aids, and they include drugs like Valium (diazepam), Xanax (alprazolam), Klonopin (clonazepam) and Ativan (lorazepam). Roughly 9% of Americans between the ages of 65 and 80 take a drug that contains benzodiazepine. But they do have significant downsides, experts caution.

First, for about one in three people who take them daily for six months or more, benzodiazepines produce significant physical dependence. This includes unpleasant withdrawal symptoms like anxiety, sleeplessness, muscle spasms, irritability and hypersensitivity.

In itself, physical dependence isn’t addiction: with physical dependence, people need a substance to function, but that is not necessarily a problem if it makes their lives better. With addiction, in contrast, people compulsively take drugs even when this makes life worse. Benzodiazepine addiction is less common than physical dependence, however, and mainly occurs in people who also misuse other types of drugs, including alcohol. Nonetheless, benzodiazepine withdrawal is notoriously difficult even without addiction. “I think people are wise to be concerned,” Morgenthaler says.

Like anticholinergics, benzodiazepines have also recently been linked to increased risk for dementia, but researchers are not convinced that the link is causal. Because both benzodiazepine use and the risk of dementia rise with age, Perlis says, the link could be simply a third variable that causes both dementia and need for sleep medication.

Other research shows that older people who take benzodiazepine are at an increased risk of falls and fractures, cognitive problems and getting into car accidents.

“The studies that exist show stable effects for up to a year without dose escalation,” says Perlis, which suggests that their effectiveness doesn’t quickly fade out. Benzodiazepines are not recommended for long-term use for most people unless none of the alternatives work.

PROS They are effective.

CONS These drugs come with a high risk of physical dependence, falls and fractures and possible risk for dementia.

THE NEW GO-TO: THE “Z” DRUGS

Another class of medications, known colloquially as the Z drugs, work on the same neurotransmitter in the brain that benzodiazepines affect, but in a slightly different way. These include Ambien (zolpidem), Lunesta (eszopiclone) and Sonata (zaleplon), and they are generally seen as safer than benzodiazepines, though there are some caveats.

“They have a lower side-effect profile and perhaps less chance for abuse,” says Watson. Some are approved for long-term use, and while “rebound insomnia” can occur when people quit, Morgenthaler says that they are easier to stop taking than the benzodiazepines.

The Z drugs have occasionally been linked with strange side effects, like driving or having sex while unconscious, but the experts emphasize that they are rare.

“The biggest concern with the Z drugs is that some patients have had sleepwalking, sleep talking and sleep driving,” says Morgenthaler. “When people first start taking them, we encourage them to be in a safe sleeping environment,” he says, in order to find out if this occurs and minimize any associated risks.

In 2012, a study published in the online edition of the British Medical Journal looked at the risks associated with zolpidem. After controlling for variables that could affect the data—age, gender, smoking, obesity, cancer history, and so on—the researcher found that people taking the drug were more than three times as likely to have died during the study period, compared with those who had not. That data does not prove causation, but it concerns some experts.

PROS The Z drugs are effective and come with less dependence risk than benzodiazepines.

CONS There is risk of “blackout” behavior and rebound insomnia; serious side effects require more research.

THE TIME SHIFTERS: MELATONIN

An additional option for sleep-deprived folks is the hormone melatonin, which can be taken in supplement form. There is also a drug called Rozerem (ramelteon), which targets melatonin receptors in the brain. Melatonin receptors help regulate the body clock that times sleep and wakefulness, and these drugs work to align your internal cycles with your sleep needs. They don’t knock you out the same way other sleep aids do.

Melatonin is often recommended for people with sleep loss associated with “out of sync” sleep like jet lag or shift work, though research does not actually support it as a jet-lag cure. Scientists have shown, however, that people who take melatonin and ramelteon fall asleep more quickly and stay asleep slightly longer than those who take a placebo pill.

PROS Rozerem is the only sleeping pill that isn’t a controlled substance, and neither the drug nor the supplement appear to cause dependence.

CONS They don’t work for everyone and can lead to day-after drowsiness.

THE OFF-LABEL Rx: ANTIPSYCHOTICS AND TRAZODONE

Though they were not approved to help people sleep, two more drugs are sometimes used for insomnia: a first-generation antidepressant approved in 1981—Desyrel (trazodone)—that appears to cause sleepiness; and medications known as “atypical” antipsychotics like Seroquel (quetiapine). When they’re prescribed for sleep, they’re being used off-label, which means that they have not been FDA-approved as sleep aids.

From a scientific perspective, little is know about the effectiveness of either as a sleep aid. In terms of risks, trazodone is linked with a rare but potentially harmful side effect in men: priapism, or an erection that lasts four or more hours and requires urgent medical attention. It can also cause drowsiness the next day, and like all antidepressants, trazodone can bring upon a host of other side effects, too.

Atypical antipsychotics are also sometimes used off-label for sleep, though a study published in 2012 found “data were inconclusive for the use of these medications for insomnia.” The drugs have been shown to increase risk for diabetes and cardiovascular disease. While they have little risk of addiction or dependence, the other side effects make them inappropriate as a first-line choice for insomnia, experts say. “They are going to have greater risk for substantial side effects,” says Watson.

PROS They have little or no addiction risk.

CONS There is not much evidence for their efficacy and could come with serious side effects.

THE NO-DRUG APPROACH: COGNITIVE BEHAVIORAL THERAPY AND MEDITATION

Physicians agree that drugs shouldn’t be the first-line treatment for insomnia, and for people who don’t want to take—or want to stop taking—pharmaceutical drugs, there is a new science-supported strategy. A review of research suggests that CBT-I, the talk therapy approach to insomnia treatment, is as effective as sleep aids and has the added benefit of being a treatment with results that last. “Medical and behavioral interventions have about the same potency during treatment,” says Perlis, one of the authors of the review. “The difference is, CBT-I effects are sustainable after treatment is discontinued.”

CBT-I has several components. The best known is sleep hygiene, which includes avoiding alcohol and late-day caffeine, reducing light exposure before bedtime (no phones or other screens) and having a regular bedtime.

People typically think of these measures—and often dismiss them as impractical or undesirable—when it comes to sleep therapy. But Perlis says they’re the least important. “It’s the weakest link,” he says, “By itself, sleep hygiene can be almost useless.”

A NEW DAY A kind of cognitive behavioral therapy called CBT-I is becoming the first line of defense against insomnia. Unlike pills, it has no side effects and can be long-lasting.

A more crucial aspect of CBT-I is sleep restriction. This means that if you know that you can sleep for only six hours, go to bed six hours before you have to get up—no sooner, no later. It also means avoiding naps or other attempts to “catch up” on sleep. And lying around worrying about your insomnia is out too. “If you can’t sleep, don’t try,” Perlis says. Instead, people whose sleep woes are due to nighttime worrying are taught ways of handling it in the moment.

Finally, there’s stimulus control. This means using your bed only for sleep and sex—and getting up as soon as you realize you can’t sleep. “You should never be in bed and awake,” Perlis says, even as he acknowledges that it is difficult to make yourself get up when you are warm and comfortable. “Get out of bed and be awake somewhere else,” he advises.

For those who seek it, CBT-I is quite effective. “In eight sessions 50% to 70% of people respond, and 30% remit,” Perlis says, meaning that most people get some relief and almost a third see their insomnia go away completely. Many insurers won’t pay for it, however, and qualified providers can be hard to find. “It makes me very sad,” he says. Online versions may help fill this gap; there’s even a free app available from the U.S. Department of Veterans Affairs, called CBT-I Coach.

There is also research that mindfulness meditation and other relaxation technique can improve the quality of sleep and ease insomnia. A randomized clinical trial—considered to be a rigorous and reliable kind of scientific research—split a group of people in two. One group underwent mindfulness training and the other was given sleep-education training. The researchers found that in the mindfulness group insomnia, depression and fatigue were significantly improved compared to the other group. The research was published this year in the journal JAMA Internal Medicine.

Whether the best course for you is meditation, supplements or drugs, the most important thing is picking one that won’t keep you up at night—literally and metaphorically.