Wake-up call for a better sleeping pill

Insomnia is an occasional problem for about a quarter of the population, but nearly one adult in 10 struggles with a chronic sleep disorder. Older people are especially vulnerable. For instance, of some 9,000 people age 65 or over who participated in a US National Institute on Aging study, only 12 percent said they had no sleep complaints. And many of these people try to deal with sleeplessness on their own. In another survey, about 70 percent of 700 insomniacs said they never told their doctors about their condition.

About a quarter of them self-medicated with alcohol, which can help them nod off, but may backfire because the brain tends to become “hyper-aroused” as the blood alcohol level drops. About the same number said they used over-the-counter medications, which are nothing more than antihistamines, drugs taken chiefly for allergies. There’s no doubt that antihistamines are sedating, but they tend to linger in the body, so you can wake up feeling groggy. Another drawback: Antihistamines also have anticholinergic effects (they interfere with the neurotransmitter acetylcholine), which in some people cause blurry vision, constipation, and confusion.

Pursuit Of The Perfect Pill

Barbiturates were once widely prescribed as sleeping pills, but “downers,” as they are often called, cause all sorts of problems, including lethal overdoses, addiction, and dangerous interactions with other drugs. So starting in the 1970s, doctors shifted to benzodiazepines, the so-called tranquilizer drugs, which include diazepam (Valium). All benzodiazepines cause sleepiness, but the FDA has approved only five varieties as sleeping pills — and Valium isn’t one of them. The major difference among them is how long they last. Some, like triazolam (Halcion in the US), stay in the blood just a few hours; others, like flurazepam (Dalmane in the US), linger for days.

Sleep induced by benzodiazepines isn’t the same as natural sleep because they tend to suppress the deeper, more restorative stages. But less-than-ideal sleep is still a blessing for people struggling with insomnia. Halcion got a bad reputation in the 1990s, after reports that it caused hallucinations and other psychiatric problems. It was yanked off the market in the Netherlands and several countries. In the US, a 1997 Institute of Medicine report concluded that it posed no greater risk than other benzodiazepines, and it’s still being sold there.

The benzodiazepines in general have gotten a bad reputation because a number of studies have identified them as causing falls, depression, and memory problems among older people. But most sleep experts say that they are safe and effective — for the short term. It’s long-term use they worry about. It’s believed that some people develop tolerance, which in this context means needing larger and larger doses to get the same effect. There’s also a risk of rebound insomnia: Once you stop taking the pills, sleeping problems come back — sometimes worse than ever. And rebound insomnia may feed the problem of dependence. People need to keep on taking the drug because if they stop, their insomnia returns with a vengeance.

The Z Drugs

So the benzodiazepines are far from perfect. Enter zolpidem (Stilnox in RP, Ambien in US), approved by the FDA in 1992 and by our own BFAD a few years later, and zaleplon (Sonata in the US), approved by the FDA in 1999 but not available in the Philippines. Sometimes they’re called non-benzodiazepines, which is a bit misleading because they work like benzodiazepines, switching on some of the same receptors on brain cells. The activated receptors release a neurotransmitter that turns off the normal neurochemical chatter among brain cells that keep us awake. But these two drugs are more selective about which receptors they bind to, and this finickiness is supposed to produce fewer side effects. They’re also shorter-acting than many of the benzodiazepines.

But whether they are much of an improvement over the short-acting benzodiazepines is debatable. Many doctors believe they are, but there are few side-to-side comparisons. Aggressive marketing and Sonata’s shortcomings (it may be a little too short-acting) have made Ambien or Stilnox the top-selling sleeping pill in the United States and the 10th best-selling prescription drug over all.

US sales of Ambien and Sonata last year exceeded $3 billion. Use of these medications and other similar drugs soared by more than 60 percent in the US since 2000, fueled by TV, print, and other advertising. Last year, makers of sleeping pills spent more than $600 million on consumer advertising. Although the FDA says that problems with the drugs are rare, reports of unusual side effects have grown as use of the sleeping pills increased.

Apparently, some users of Ambien have complained about unusual reactions — ranging from fairly benign sleepwalking episodes to hallucinations, violent outbursts, nocturnal binge eating and — most troubling of all — driving while asleep. Night eaters said they woke up to food snack wrappers in their beds, kitchen counters covered with flour from baking sprees, and lighted stoves. Sleepdrivers reported frightening episodes in which they recalled going to bed but woke up to find they have been arrested roadside in their underwear or nightclothes. Other strange reports include purchasing items over the Internet and having sex under the influence of sleep medication!

The FDA said it was not aware of any deaths caused by sleepdriving. Dr. Russell Kutz, the FDA’s director of neurology products, said drinking alcohol before or after taking the drugs appears to increase the chances of having such unusual reactions.

Nonprescription remedies include melatonin, a hormone your pineal gland produces at night as a kind of natural sleeping potion. But it’s questionable how effective synthetic melatonin is as a sleeping pill. Some research suggests that it may be helpful when the circadian rhythms that govern your natural sleep-wake cycle are out of adjustment because of jet lag from travel.

The Next-Generation Sleeping Pills

Whatever their virtues, zolpidem and zaleplon are FDA-approved for short-term use only and that means they can’t legally be marketed for long-term use. In actual practice though, many people take them — and the benzodiazepines — for months or even years. In fact, by some estimates, 14 percent of people treated for insomnia have taken some kind of sleeping pill for more than a year. Meanwhile, as studies reveal the negative health consequences of insomnia and not getting enough sleep, the risk benefit calculus of sleeping pills is changing. Their drawbacks have to be weighed against the consequences of not treating chronic sleeping problems. All of this adds up to a great deal of interest in identifying drugs that could win approval as long-term sleeping pills.

Right now, there are two leading candidates, eszopiclone and indiplon. Most studies on sleeping pills last only a few weeks. Sepracor, the company that makes eszopiclone, has plowed millions of dollars into studies that have lasted six months and sometimes longer. Their initial studies showed that the drug helped with a variety of sleep problems and, the authors said, with no evidence of tolerance. It may well be the product that pioneers the market for long-term sleeping pills. Chemically, eszopiclone is not a pioneer, though, being simply a close relative to zolpidem.

Worries And Dangers

What worries doctors though is that our eagerness to have pills for every medical condition may result in the further overuse of sleeping pills. Insomnia can be its own condition, but sometimes it’s a symptom of other problems, such as depression or arthritis. Rather than paper over such problems with a sleeping pill, skeptics ask, wouldn’t it be better to treat the root cause? Some people have trouble sleeping because of bad habits: drinking caffeine too late in the day (noon is a good cutoff point), not going to bed at a regular time, or not getting enough exercise. Trying to break such habits before resorting to a sleeping pill makes sense.

Finally, relaxation techniques, meditation, or yoga appear to relieve the stress that has built up during the day and help many people sleep better. Because insomnia is often caused by anxiety — and indeed, anxiety about not sleeping — therapies that relieve anxious feelings benefit some tossers and turners. But as many sleep experts have observed, success may require many hours of work with a counselor — and also considerable discipline on the part of the patient. “A large percentage of people are just not interested,” they say. “They just want to get the problem fixed.” For them, a supposedly problem-free, long-term sleeping pill is going to be very tempting!