Classification & Clinical Findings
Patients may complain of difficulty getting to sleep or staying asleep, intermittent wakefulness during the night, early morning awakening, or combinations of any of these. Transient episodes are usually of little significance. Stress, caffeine, physical discomfort, daytime napping, and early bedtimes are common factors.
Psychiatric disorders are often associated with persistent insomnia. Depression is usually associated with fragmented sleep, decreased total sleep time, earlier onset of REM sleep, a shift of REM activity to the first half of the night, and a loss of slow wave sleep—all of which are nonspecific findings. In manic disorders, a reduced total sleep time and a decreased need for sleep are cardinal features and important early sign of impending mania. In addition to a decreased amount of sleep, manic episodes are characterized by a shortened REM latency and increased REM activity. Sleep-related panic attacks occur in the transition from stage 2 to stage 3 sleep in some patients with a longer REM latency in the sleep pattern preceding the attacks.
Abuse of alcohol may cause or be secondary to the sleep disturbance. There is a tendency to use alcohol as a means of getting to sleep without realizing that it disrupts the normal sleep cycle. Acute alcohol intake produces a decreased sleep latency with reduced REM sleep during the first half of the night. REM sleep is increased in the second half of the night, with an increase in total amount of slow wave sleep (stages 3 and 4). Vivid dreams and frequent awakenings are common. Chronic alcohol abuse increases stage 1 and decreases REM sleep (most medications delay or block REM sleep), with symptoms persisting for many months after the individual has stopped drinking. Acute alcohol or other sedative withdrawal causes delayed onset of sleep and REM rebound with intermittent awakening during the night.
Heavy smoking (more than a pack a day) causes difficulty falling asleep—apparently independently of the often associated increase in coffee drinking. Excess intake near bedtime of caffeine, cocaine, and other stimulants (eg, over-the-counter cold remedies) causes decreased total sleep time—mostly NREM sleep—with some increased sleep latency.
Sedative-hypnotics—specifically, the benzodiazepines, which are the most commonly prescribed medications to promote sleep—tend to increase total sleep time, decrease sleep latency, and decrease nocturnal awakening, with variable effects on NREM sleep. Nonbenzodiazepine hypnotics have similar effects on sleep as do the benzodiazepines, though some evidence shows improved slow wave sleep and less residual next-morning somnolence with non-benzodiazepines, such as zolpidem. Withdrawal causes just the opposite effects and results in continued use of the drug for the purpose of preventing withdrawal symptoms. Antidepressants decrease REM sleep (with marked rebound on withdrawal in the form of nightmares) and have varying effects on NREM sleep. The effect on REM sleep correlates with reports that REM sleep deprivation produces improvement in some depressions.
Persistent insomnias are also related to a wide variety of medical conditions, particularly delirium, pain, respiratory distress syndromes, uremia, asthma, thyroid disorders, and nocturia due to benign prostatic hyperplasia. Sleep apnea and restless leg movement are described below. Adequate analgesia and proper treatment of medical disorders will reduce symptoms and decrease the need for sedatives.
In general, there are two broad classes of treatment for insomnia, and the two may be combined: psychological (cognitive-behavioral) and pharmacologic. In situations of acute distress, such as a grief reaction, pharmacologic measures may be most appropriate. With primary insomnia, however, initial efforts should be psychologically based. This is particularly true in the elderly to avoid the potential adverse reactions of medications. The elderly population is at risk for complaints of insomnia because sleep becomes lighter and more easily disrupted with aging. Medical disorders that become more common with age may also predispose to insomnia.
Psychological strategies should include educating the patient regarding good sleep hygiene: (1) Go to bed only when sleepy. (2) Use the bed and bedroom only for sleeping and sex. (3) If still awake after 20 minutes, leave the bedroom, pursue a restful activity (such as a bath or meditation), and only return when sleepy. (4) Get up at the same time every morning regardless of the amount of sleep during the night. (5) Discontinue caffeine and nicotine, at least in the evening if not completely. (6) Establish a daily exercise regimen. (7) Avoid alcohol as it may disrupt continuity of sleep. (8) Limit fluids in the evening. (9) Learn and practice relaxation techniques. (10) Establish a bedtime ritual and a routine time for going to sleep. Research suggests that cognitive behavioral therapy for insomnia is as effective as zolpidem with benefits sustained 1 year after treatment.
When the above measures are insufficient, medications may be useful. Lorazepam (0.5 mg orally nightly), temazepam (7.5–15 mg orally nightly), and the nonbenzodiazepine hypnotics zolpidem (5–10 mg orally nightly, with a limit of 5 mg indicated for women) and zaleplon (5–10 mg orally nightly) are often effective for the elderly population and can be given in larger doses—twice what is prescribed for the elderly—in younger patients. Zaleplon is often used to treat insomnia characterized by middle-of-the-night awakening with difficulty falling back to sleep. Eszopiclone (2–3 mg orally) is similar in action to zolpidem and zaleplon and has a longer duration of action. A lower dose of 1 mg is indicated in the elderly or those with hepatic impairment. It is important to note that short-acting agents like triazolam or zolpidem may lead to amnestic episodes if used on a daily ongoing basis. Longer-acting agents such as flurazepam (half-life of more than 48 hours) may accumulate in the elderly and lead to cognitive slowing, ataxia, falls, and somnolence. In general, it is appropriate to use medications for short courses of 1–2 weeks. The medications described above have largely replaced barbiturates as hypnotic agents because of their greater safety in overdose and their lesser hepatic enzyme induction effects. Antihistamines such as diphenhydramine (25 mg orally nightly) or hydroxyzine (25 mg orally nightly) may also be useful for sleep, as they produce no pharmacologic dependency; their anticholinergic effects may, however, produce confusion or urinary symptoms in the elderly. Trazodone, an atypical antidepressant, is a non–habit-forming, effective sleep medication in lower than antidepressant doses (25–150 mg orally at bedtime). Priapism is a rare side effect requiring emergent treatment. Doxepin, 3–6 mg per night, is a TCA that is also effective for insomnia. Ramelteon, 8 mg orally at bedtime, is a melatonin receptor agonist that helps with sleep onset and does not appear to have abuse potential. It appears to be safe for ongoing use without the development of tolerance.
Triazolam was popular as a hypnotic medication because of its very short duration of action. However, because it has been associated with dependency, transient psychotic reactions, anterograde amnesia, and rebound anxiety, it has been removed from the market in several European countries. If used, it should be prescribed only for short periods of time.
The dual orexin receptor antagonists (DORAs) class of hypnotics are approved to help initiate and maintain sleep. DORAs such as suvorexant may be more effective than other hypnotics for some patients. However, the role of suvorexant has not been established relative to other hypnotics and is more expensive since it is not generically available. DORAs have shown a significant increase in depressive symptoms in a subset of patients, so other hypnotics may be a better choice in depressed patients. The dose of suvorexant is 10–20 mg orally given about 30 minutes before bedtime.