New benzodiazepine receptor agonists for chronic insomnia–zaleplon, zolpidem, and eszopiclone–have shown fewer adverse effects compared with other medications, but additional studies are needed to assess these drugs' long-term effectiveness, concluded members of an independent panel convened by the National Institutes of Health in Bethesda, Md.
Only eszopiclone (Lunesta) has been approved for the long-term treatment of insomnia; the other drugs are approved for up to 35 days of use.
Five benzodiazepines–estazolam, flurazepam, quazepam, temazepam, and triazolam–also are approved by the Food and Drug Administration to treat insomnia, but adverse events including dependence, daytime sleepiness, and lack of motor coordination are more likely with these drugs than with the new receptor agonists.
Although commonly used, all of these medications require more research.
“The real problem with these kinds of compounds is that there are very few data on their efficacy in the treatment of chronic insomnia, yet we know from other research that they produce substantial side effects,” panel member Robert J. DeRubeis, Ph.D., said in an interview.
After reviewing information on the latest research and the available treatments, the panel members concluded that limited guidance and resources exist for clinicians about the treatment of chronic insomnia. They emphasized that more research is needed on the available treatment methods, which include hypnotic medications, behavioral therapy, and alternative medicine, as well as antidepressants, antihistamines, and antipsychotics.
Given the availability of treatments with demonstrated efficacy and fewer side effects in the short term, the panel could not recommend off-label use of nonapproved substances, said Dr. DeRubeis, chair of the department of psychology at the University of Pennsylvania in Philadelphia.
Antidepressants, particularly trazodone, are often prescribed off label for insomnia, but there are no data on the effects of long-term use of such agents, the panelists noted.
“Trazodone is not without danger,” panel member James N. Kvale, M.D., a professor in the department of family and community medicine at the University of Texas, San Antonio, said in an interview. “It loses effectiveness as a sleep aid after 7 days, and its real value for the chronically ill person is to be questioned.”
Chronic sleep loss is a public health problem associated with impaired psychomotor and cognitive function, and may contribute to the risk of falls in older adults, the panelists wrote in a draft consensus statement.
In addition, millions of Americans attempt to treat their sleep problems for prolonged periods of time with untested or off-label products including alcohol and antihistamines, despite a lack of evidence for their effectiveness.
Doctors can start by advising sleepless patients to consider environmental factors, including temperature, light, and sound in the bedroom. If problems persist, doctors should consider referring patients for cognitive-behavioral therapy before prescribing medications, Dr. Kvale said. Given the lack of evidence to support even the approved drug treatments for long-term use, it's important to explore nonpharmaceutical ways to manage sleep problems, he explained.
Cognitive-behavioral therapy (CBT) has proved successful for managing insomnia in randomized, controlled trials. Use of CBT involves training in relaxation, controlling external stimuli, and targeting anxiety-inducing beliefs about sleep and sleep loss. But few clinicians are experts in treating chronic insomnia with CBT, and these techniques are not widely used, the panelists noted.
Although CBT and benzodiazepine receptor agonists have shown benefits in patients with chronic insomnia, additional research is needed to compare the various treatments with each other, and to determine the effectiveness of the treatments across different populations.
The hormone melatonin and the herb valerian have been used for insomnia, but neither of these substances is regulated by the FDA, and the variation in content among preparations makes scientific comparison difficult.
Other alternative treatments for insomnia include light therapy, acupuncture, yoga, and tai chi, but none of these have been sufficiently evaluated, the panel said in the draft statement.
To close the gaps in knowledge, the panel recommended that future studies be randomized, controlled trials comparing at least two effective or promising treatments, including drugs, CBT, and combination therapies.
Understudied features of chronic insomnia include its effects on daytime functioning that prevent people from engaging in a productive and enjoyable work and social life, Dr. DeRubeis added.
Little is known about the incidence of chronic insomnia because it can be difficult to identify as a distinct problem, as opposed to a side effect of other conditions or medications. For example, a middle-aged woman with arthritis may have trouble sleeping, but she talks to her doctor about her arthritis without mentioning insomnia. Population-based studies suggest that about 30% of the general population complain of sleep problems, the panelists noted.