Conventional wisdom holds that insomnia is a symptom, not a disorder. But new evidence suggests insomnia may constitute a distinct clinical syndrome on its own, according to Daniel Buysse, M.D., a professor of psychiatry at the University of Pittsburgh.
About one-third of adults report persistent difficulty falling and/or staying asleep, poor quality sleep, or too little sleep, that is, an inability to sleep even though they have an adequate opportunity to do so. About 10 percent to 15 percent of adults—and 25 percent of those aged 65 and over—say they sleep poorly most nights or every night. Most insomniacs also report problems with daytime fatigue, mood, and performance.
"Physicians, even psychiatrists, seldom diagnose primary insomnia in these patients," Buysse said. "They’re more apt to see the problem as depression or anxiety."
But sometimes poor sleep is only poor sleep, Buysse suggested. Insomnia may be secondary to psychiatric or medical disorders, medications, or substance use. It is associated with sleep apnea, restless legs syndrome, and circadian rhythm disorders. As many as 5 percent of adults may have primary insomnia; some report being lifelong "light" sleepers.
Regardless of type or etiology, Buysse said, insomnia symptoms and daytime consequences prove similar. Moreover, "insomnia often has a life of its own," he noted, while comorbid illnesses wax and wane. Insomnia also responds to different types of treatment than do comorbid disorders.
Buysse was one of several speakers to address psychiatric aspects of sleep disorders at a conference sponsored by the National Center on Sleep Disorders Research at the National Institutes of Health in March. Conferees sought to translate findings from sleep studies into practical guidelines to improve public health and quality of life.
There may be physiological differences between good and poor sleepers, Buysse said. Compared with good sleepers, people with primary insomnia secrete more cortisol in the evening before bedtime and in the first half of their sleep; they also have more fast brain-wave activity in non-rapid eye movement (NREM) sleep, both indicators of arousal. Preliminary evidence from PET studies by psychiatrist Eric Nofzinger, M.D., also at the University of Pittsburgh, suggests that insomniacs have whole-brain hypermetabolism in NREM sleep and while awake, according to a study in press in the American Journal of Psychiatry.
Insomnia has important health consequences, including increased health care utilization and costs and a higher risk of workplace accidents and car crashes, Buysse noted. It is associated with falls and hip fractures independently of hypnotic use and lowers quality of life as much as congestive heart failure and clinical depression do. Healthy older adults who take more than 30 minutes to fall asleep have twice the risk of death at four to 19 years of follow-up as people who fall asleep faster.
Behavioral tactics that include restriction of time in bed to time spent asleep, establishment of a regular wake-up time, regular exercise, and limiting use of caffeine and alcohol benefit many patients, Buysse said. New thinking on primary insomnia will be addressed in the second edition of the International Classification of Sleep Disorders, scheduled for publication in August by the American Academy of Sleep Medicine.
Ruth Benca, M.D., Ph.D., a professor of psychiatry at the University of Wisconsin at Madison, also speaking at the meeting, said sleep disturbances are more strongly associated with psychiatric disorders than with any other illness. People with mood disorders show more extensive and robust changes in sleep compared with individuals with anxiety disorders, eating disorders, or schizophrenia. These changes include more frequent awakenings, reduced slow wave sleep, shorter latency to REM sleep, and an increased number of eye movements in REM sleep. These findings, though of research interest, lack sensitivity and specificity for clinical use.
About three in four patients with insomnia have a psychiatric disorder as a primary or secondary diagnosis, she reported. Insomnia precedes first episodes of depression about 40 percent of the time and heralds more than half of relapses in recurrent depression. In anxiety disorders, it tends to follow onsets or relapses. It also predicts an increased risk of suicidal ideation or behavior. Insomnia precedes three of four onsets of mania.
About 3 percent of the general adult population have hypersomnia; half of them also have psychiatric disorders, including depression, Benca said. People with a history of both insomnia and hypersomnia have higher rates of psychiatric illnesses than those who have either alone.
People with other sleep disorders, including narcolepsy, restless legs syndrome, and sleep apnea, also have higher rates of anxiety and depression than healthy sleepers.
Sleep deprivation worsens mood in normal subjects. Paradoxically, it improves mood in severely depressed people, particularly when timed to the latter half of the night. Sleep deprivation can worsen or precipitate mania in people with bipolar disorder.
By 2020, major depression is predicted to be the second leading cause of disability worldwide. The insomnia-depression link, Benca asserted, should increase attention to sleep in medical settings.
Physician-patient encounters associated with psychiatric disorder codes result in more prescriptions for hypnotics than those associated with insomnia codes, reported W. Vaughn McCall, M.D., M.S., professor and chair of psychiatry and behavioral medicine at Wake Forest University School of Medicine in Winston-Salem, N.C.
McCall and colleagues analyzed data from the National Ambulatory Medical Care Survey, 1990-1998. Physicians seldom diagnose primary insomnia, the researchers found. Adult primary care offices account for 55 percent of hypnotic encounters, and psychiatric offices, 12 percent. Specialty-care offices generate the rest.
The data underscore the relevance of mental disorders to the prescribing of hypnotics, McCall said. Most data on hypnotic efficacy, however, come from studying people with primary insomnia, who receive the fewest hypnotic prescriptions.
Insomnia accompanying a psychiatric disorder may stem from a medical cause, medications, a conditioned response, or primary sleep disorder, he noted. While insomnia is a criterion symptom for a major depressive episode, dysthymia, mania, and generalized anxiety disorder, it’s not required for diagnosis. Daytime symptoms of depression differentiate depressed insomniacs from those with primary insomnia.
Physicians need to target insomnia in their treatment, McCall asserted. In patients with both insomnia and other psychiatric disorders, treating insomnia often brings greater overall improvement than does treating the other disorders alone.
Selective serotonin reuptake inhibitors commonly used to treat depression may not relieve insomnia, McCall cautioned; indeed, 10 percent of users develop treatment-emergent insomnia. Thus, patients remain at risk of recurrences of their psychiatric disorder.
No hypnotics have Food and Drug Administration approval for treatment lasting more than five weeks, he noted. Open-label trials of zaleplon and zolpidem and controlled trials of eszopiclone show continued hypnotic efficacy for six months without late-emerging side effects in psychiatric and general practice patients.
Aiming to improve their alertness or sleep, some people self-administer drugs such as stimulants and alcohol, said Timothy Roehrs, Ph.D., a professor of psychiatry and behavioral neurosciences at Wayne State University in Detroit. Some may develop behavioral and/or physiological dependence and move on to substance abuse.
To differentiate therapy-seeking from drug-seeking behavior, Roehrs and colleagues have conducted a series of studies using sleepiness as a stimulus to drug-taking behavior and disturbed sleep as a condition for alcohol use.
In one study, for example, healthy, normal, well-rested subjects first had the opportunity to sample color-coded pills containing methylphenidate, 10 mg, or a placebo. Subjects were told the capsules they sampled could be a stimulant, a depressant, or a placebo. The participants rated the methylphenidate as amphetamine-like. The drug also had physiologically alerting effects: subjects taking the drug proved more alert across the day when assessed with a standard sleep laboratory test than they were when they did not take the drug.
They then were given the opportunity to take the same pills after spending either eight or four hours in bed. After eight hours in bed, they chose placebo about 80 percent of the time, and methylphenidate 20 percent of the time. After four hours in bed, they chose methylphenidate about 80 percent of the time, and placebo less than 20 percent of the time. In the eight-hour condition, Roehrs said, subjects experience methylphenidate as a stimulant, even though it does not improve their physiological daytime alertness, as measured by the standard test.
In a study now in progress, the researchers hope to learn whether the experience of self-administering the drug when sleepy increases the likelihood of taking it later, when alert. The choice, Roehrs said, may depend on the nature of behavioral demands placed on them in the daytime, that is, whether they are asked to perform a vigilance task, relax, or sleep.
In another study, subjects with primary insomnia and healthy controls were allowed to consume ethanol or placebo before bedtime and to take refills of their chosen beverage. The ethanol doses were small; even with refills, subjects could increase their blood alcohol to only .06 percent. The level of legal intoxication in most states is .08 percent.
Compared with control subjects, insomniacs chose ethanol on more nights and drank more ethanol refills. Ethanol improved sleep on the first two nights, but subjects developed tolerance by the sixth night. After six nights, they increased the number of alcohol refills.
The vast majority of people receiving standard hypnotics use them therapeutically, Roehrs noted, and do not develop tolerance, as occurs with use of alcohol as a sleep aid. Most of the small percentage of people who use hypnotics chronically do not escalate the dose. The defining characteristic of drug seeking, Roehrs said, is that users choose the drug more frequently than they do a placebo, escalate the dose, and then use the drug outside of the therapeutic context.
Physicians need to monitor patients’ complaints about sleep or daytime alertness, Roehrs asserted, to avoid conversion of what is initially therapy-seeking to drug-seeking behavior.
Conferees at the tmeeting developed action plans to boost physician and public awareness of current knowledge about sleep and apply it to medical practice and daily life. The group that focused on psychiatric disorders, under Buysse’s direction, called for promoting recognition of good sleep’s contribution to mental health—and vice versa. It also recommended development of a standard of care for the diagnosis and treatment of insomnia across the lifespan, with attention to measures of nighttime sleep and daytime functioning as important outcomes.
Other work groups developed action plans to utilize sleep knowledge to improve learning and memory, workplace and driving performance, and prevention and treatment of cardiovascular disease, obesity, and diabetes.
A videocast of the conference may be accessed at http://videocast.nih.gov/PastEvents.asp?c=26. ▪