For Some Insomniacs, "Z Drugs" Bring On More Than Just Sleep

Sleeping pill sales have increased dramatically in the past year - in part due to hundreds of millions of dollars spent on direct advertising to consumers. Several of the newer "hypnotic" sleep medications - called "Z drugs" - might be better than the earlier generation of sleep medications. But new reports of lives nearly destroyed due to side effects of one of these Z drugs have surfaced in the past few weeks. The drug Ambien has been in the news because of case reports in a medical journal. Patients - in their sleep - have been walking or driving or relentlessly raiding the refrigerator. Newspapers have recounted patient stories of Ambien-induced impairment and misadventures. These include shoplifting, automobile accidents and other behaviors sure to embarrass the perpetrators if they could only remember what happened. In fact, sleepwalking was identified in the Ambien clinical trials leading to marketing approval by the US Food and Drug Administration (FDA), and it is listed as a rare side effect on the package insert. But the accumulating case reports are arousing speculation that sleepwalking and other impaired behaviors may be less rare than they first appeared to be in clinical trials. Despite the recent case reports, UCSF researchers and clinicians who are familiar with sleep medications are reluctant to single out Ambien as a special risk. "Sleeping pills are generally safe and effective when they are used as directed," notes Louis Ptacek, MD, a professor of neurology and Howard Hughes Medical Institute investigator at UCSF who studies the genetic and biochemical mechanisms that lead some individuals to sleep odd hours. "All sleep medications have the potential to cause some side effects," adds David Claman, MD, associate clinical professor of medicine who directs the Sleep Disorders Center at UCSF. "I continue to feel that Ambien is generally a safe medication." According to Patrick Finley, PharmD, professor of clinical pharmacy, psychopharmacology and behavioral health at UCSF, Ambien can come on strongly, perhaps taking some users by surprise. Depending on the dose, users may feel no effect - or a big effect. "There is a therapeutic threshold," Finley says. The dose is either subtherapeutic or definitely therapeutic - meaning within 15 minutes of taking it, you really need to find your bed." Adverse Side Effects Strange side effects are not unique to Ambien. An older sleep medication, Halcion, occasionally causes uncharacteristically aggressive behavior and amnesia among some users. Though it was a bestseller 15 years ago, postmarketing case reports contributed to Halcion's slide from popularity.

Halcion is a benzodiazepine. These drugs - also including Valium, Restoril and Dalmane - pose risks that contribute to physicians' being less likely to prescribe them. Benzodiazepines are regarded as being imprecisely targeted. They attach to the benzodiazepine receptor on brain cells in a way that leads to sleep. But they also attach elsewhere - a recipe for side effects. In fact, they also are used as muscle relaxants and antiseizure medications. Frequent or habitual benzodiazepine use can lead to tolerance - having to use increasing amounts to get to sleep - and to addiction. And while alcohol worsens the mental impairment induced by all sleeping pills, benzodiazepines and alcohol are an even worse combination. "Benzodiazepines taken alone are not a great death risk, but when used with alcohol, all bets are off," Finley says. Still, he adds, it is not clear whether the newer Z drugs - so-called because their generic names feature the letter Z - more effectively induce sleep: "I think if you look for primary research published in the scientific literature, you would be appalled by the paucity of comparative trials. There's really very little data there." Sleeping pills have for decades only been marketable for short-term use. They are not meant to be used for more than seven to 10 consecutive nights. As newer drugs come on line with less obvious side effects and less potential to cause addiction, the FDA, physicians and patients may become less concerned with limiting their use. And legions of drug reps charged with drumming up sales undoubtedly will continue spreading the message that insomnia is severely debilitating, underdiagnosed and undertreated. Not Standard Treatment But regardless of how widespread or underdiagnosed insomnia may be, sleeping pills are not yet regarded by any class of medical professionals as the first-line treatment for insomnia. That's one message unlikely to be widely disseminated any time soon via a multimillion-dollar ad campaign. Sleeping pills are considered most appropriate for times when one's routine is unavoidably disrupted - as by travel or hospitalization. Sleeping pills do not address the underlying causes of recurrent sleeplessness, which often include troubling life situations. Claman and Finley both point to published scientific research which indicates that cognitive behavioral therapy generally is more effective than sleeping pills in treating insomnia. But even without going for therapy aimed at changing unhealthy behaviors or thought processes, insomniacs may benefit by trying to practice "good sleep hygiene." In its simplest form, here is a checklist of do's and don'ts. Abiding by these simple rules increases the likelihood of getting a good night's sleep. In the course of his sleep disorders research, Ptacek has found that individuals vary quite a bit in how familiar they are with good sleep habits. A large majority know that caffeine can disrupt sleep, but other precautions are less familiar. In addition, he notes, behaviors that increase one's chances of sleeping well are not always embraced, even when they are familiar. Just as many dieters yearn for a pill that would eliminate the need to exercise or to limit calorie intake, many insomniacs may prefer sleeping pills to prohibitions on caffeine, alcohol, late night snacks or spontaneously irregular hours. Sleeping pills may be the option of last resort. As Claman concedes, "Medications are needed for some people who don't respond to behavioral modifications." Source: Jeff Norris Links: Sleep Disorders Center