Assessment and Management of Insomnia

Insomnia is a common treatable disorder of insufficient or poor-quality sleep, with adverse daytime consequences.¹ Insomnia presents as trouble falling asleep (long-sleep latency), trouble staying asleep (excessive or prolonged awakenings), or feeling nonrestored from sleep. Insomnia can be a primary disorder emerging in childhood or later, a conditioned (psychophysiological) disorder, or comorbid with a psychiatric, medical, or other sleep disorder.¹ Insomnia can be transient (related to stress, illness, travel) or chronic (occurring nightly for >6 months). Persistent untreated insomnia is a strong risk factor for major depression.² Insomnia must be distinguished from sleep-state misperception and short sleep states without symptoms.¹

More than 50 epidemiological studies have shown that one third of various general populations have insomnia symptoms and that 9% to 21% have insomnia with serious daytime consequences, such as bodily fatigue, diminished energy, difficulty concentrating, memory impairment, low motivation, loss of productivity, irritability, interpersonal difficulties (with family, friends, coworkers), increased worrying, anxiety, and depression.^{3 - 5} Chronic sleep loss, which occurs in untreated insomnia, is a major risk factor for fatigue-related automobile crashes and industrial accidents, loss of jobs, marital and social problems, poor health, metabolic and endocrine dysregulation with impaired ability to maintain weight control, coronary heart disease, major depression, and suicidality.^{6 - 8} Insomnia is associated with enormous direct and indirect costs, as much as $14 billion in the United States in 1995.⁷ Physicians should therefore establish an effective clinical strategy for eliciting and managing insomnia complaints.^{9 - 11} Use of a sleep-trained nurse, psychologist, or both on a consultation basis or as a member of the physician's medical practice should be considered. One study has reported on the benefit of behavioral treatment of insomnia provided by a trained clinic nurse in a general medical practice.¹² However, the cost-effectiveness of incorporating a sleep-trained nurse or psychologist into a medical practice has yet to be reported.

Assessment of insomnia complaints should begin with a history obtained from the patient and bedpartner, then continue with a physical examination. The primary focus should be on the functional impact and severity, and chronicity of the complaints, with rapid identification of target symptoms for use in formulating a management strategy. Questioning should be directed at determining age of onset, predisposing factors and traits (family history, habitual light sleeper, sensitivity to noise and other stimuli, deviant circadian sleep and wake rhythm), precipitating events (stress, illness, medication, or bedpartner's sleep problem), duration and specific characteristics (nightly, intermittent, or situation-specific: weekday vs weekend, with vs without bedpartner, sleep at home vs away, time-of-night pattern, and daytime consequences). Life-style, daily activity patterns, and maladaptive behaviors must be addressed, including the frequency, timing, and type of meals consumed. Timing of sexual activity and exercise, and any other effect on sleep, should also be explored. The bedpartner's input can provide important information regarding snoring and breathing patterns, unusual sleep motor activity, and daytime consequences from suboptimal sleep. Use of caffeine, alcohol, and drugs (prescription, over-the-counter, herbal products, illicit agents) should also be discussed. Reliving a typical day with the patient can be helpful.

A sleep log (diary), completed for at least 7 consecutive days, is important for evaluating an insomnia complaint¹¹ and is especially useful in identifying circadian rhythm disorders as a cause of insomnia. A sleep questionnaire is also useful; a commonly used one is the Pittsburgh Sleep Quality Index¹³ that has 19 items yielding data on the severity of insomnia. Urine toxicology screening may be needed in selected cases to detect use of stimulant drugs (ephedrine, cocaine, amphetamines).

Psychological screening should assess the presence and severity of depression and anxiety, which are the most common psychiatric conditions associated with insomnia. The Beck Depression and Beck Anxiety Inventories are simple, validated, self-administered tests with easy guidelines for physician interpretation.¹¹ Such tests should be administered to insomnia patients with suspected depression and anxiety or to patients with no identified cause of insomnia. Formal psychological or psychiatric referral can be considered on a case-by-case basis. Patients with a past or current history of psychiatric disorder who present with an insomnia complaint should most likely be referred to a psychiatrist to assess whether a psychiatric disorder is contributing to the insomnia complaint.

Actigraphy is an objective test that is useful in identifying sleep-state misperception, sleep-interruption insomnia, and circadian rhythm disorders. Actigraphy uses a wrist monitor that records movement during successive 1-minute time bins on a microcomputer chip. The movement and nonmovement pattern can correlate closely with wakefulness and sleep.¹¹ Nevertheless, there can be substantial error in some insomniacs who lie quietly in bed for prolonged periods of time.¹¹ Polysomnography (formal physiological monitoring of sleep) should be reserved for cases of insomnia with a suspected organic sleep disorder. The use of actigraphy and polysomnography should be decided during a consultation with a sleep specialist.

A common cause of persistent insomnia is conditioned (learned or psychophysiological) insomnia. This disorder usually arises from an episode of acute situational insomnia (triggered by pain, illness, medication, stress, travel, bereavement). The patient soon associates the bed with not sleeping and becomes hyperaroused at night at a time when he/she would ordinarily feel relaxed and sleepy. After the original precipitant recedes, a conditioned insomnia persists that will often not resolve spontaneously.

Insomnia is very common in psychiatric disorders, particularly mood and anxiety disorders.^{2 ,4 ,7} In 1 large study, insomnia appeared before the onset of a mood disorder in more than 40% of affected persons, whereas insomnia appeared concurrently or after the onset of an anxiety disorder in more than 72% of affected persons.⁴ Medical disorders and sometimes their treatment most commonly associated with insomnia include asthma, chronic obstructive pulmonary disease, congestive heart failure, ischemic heart disease, gastroesophageal reflux, rheumatologic or other pain-related disorders, hyperthyroidism, end-stage renal disease, and neurodegenerative disorders.^{7 ,14 - 15} Nocturnal gastroesophageal reflux can be an epiphenomenon of obstructive sleep apnea, improving with treatment of the latter condition.¹⁶

The most common sleep disorder associated with sleep-onset and sleep-maintenance insomnia is restless legs syndrome, which at times is linked with disruptive periodic limb movements of sleep, obstructive sleep apnea, and parasomnias (sleep behavior disorders).^{17 - 18} Restless legs syndrome affects up to 10% of the general population and more than 25% of pregnant women and often results in severe insomnia.¹⁷ Restless legs syndrome manifests as peculiar, distressing, and painful leg sensations during drowsiness that are relieved by walking or other measures that are incompatible with falling asleep. Dopaminergic or opiate therapy, or both (and at times use of benzodiazepines, particularly clonazepam) at bedtime is usually effective, safe, and well-tolerated during long-term nightly use.^{17 - 20} The common and quite treatable parasomnias include abnormal behaviors associated with obstructive sleep apnea¹⁷ ; disorders of arousal from non–rapid eye movement sleep (sleepwalking, sleep terrors); rapid eye movement sleep behavior disorder (acting-out of violent dreams, usually in older men); and nocturnal sleep-related eating disorders (consumption of high-calorie foods during partial nocturnal arousals, usually in women). Screening questions for parasomnias are available for physician use.¹⁸ A related phenomenon involves bedpartner-induced or aggravated insomnia, due to snoring, body jerking, periodic leg movements, or parasomnias.

Caretaker insomnia can emerge in various contexts. Parents of newborns who have repeated nocturnal awakenings or adults who must care for spouses or family members with medical disorders associated with sleep disruption often complain of insomnia with daytime consequences. The physician must assess the value of various treatment modalities for a particular patient: a low-dose sedative (0.125/0.25 mg of alprazolam; 0.5 mg of lorazepam) at bedtime may facilitate the prompt resumption of sleep throughout multiple caretaking-related awakenings; zaleplon (5-10 mg) as occasion requires can help control any tendency for prolonged awakenings; strategic daytime naps (15-45 minutes), depending on the napping capabilities of the individual and the schedule of daily activities; and judicious use of caffeine in the morning or early afternoon to increase alertness. However, prolonged naps or naps taken late in the day could aggravate insomnia, as could excessive amounts or ill-timed use of caffeine. Regular exercise should also be encouraged, provided that the timing of the exercise does not interfere with sleep.

The diagnostic and management strategies of insomnia are linked. The physician should promptly place an insomnia complaint into 1 of 4 categories (not mutually exclusive): related to stress, bad habits, or improperly timed activities; related to a sleep disorder (chronic insomnia, circadian rhythm disorder, obstructive sleep apnea, restless legs syndrome and periodic limb movements disorder, parasomnia); related to a medical, neurological, psychiatric disorder; and nonclinical complaint, without daytime consequence (short sleeper; some cases of sleep-state misperception). The physician can then decide whether to further evaluate and treat the insomnia or refer the patient to a specialist.

Transient insomnia can be controlled with short-term use of a hypnotic medication. Management of persistent or chronic insomnia can be separated into primary and secondary interventions ( Article ). Sleep hygiene aims to establish proper daily habits that promote sleep and minimize daily habits that interfere with sleep (eg, drinking coffee or engaging in stressful activities in the evening).^{2 ,7} Relaxation training can take various forms (progressive muscle relaxation, guided imagery, hypnosis, meditation, yoga, biofeedback), with the goal being the reduction of psychic and muscular tension causing hyperarousal and interference with sleep onset.^{2 ,7} Stimulus-control therapy is directed both to reducing arousing stimuli in the bedroom that interfere with falling asleep and reinforcing associations between the bed/bedroom and falling asleep.^{2 ,7} Various unproven interventions are widely promoted and some, such as white noise machines, may be helpful in selected cases (noise-sensitive insomnia).

Primary Interventions
 Sleep hygiene training
 Relaxation training
 Stimulus-control therapy

Secondary Interventions
 Pharmacologic
 Zolpidem and zaleplon
 Benzodiazepine hypnotics and anxiolytics
 Antidepressants
 Combined pharmacotherapies
 Nonpharmacologic
 Cognitive-behavioral therapy
 Sleep restriction and sleep consolidation therapy

When primary interventions are ineffective or partially effective in controlling insomnia, secondary interventions should be considered. Depending on patient interest and physician training, either pharmacologic or nonpharmacologic interventions can be successfully used. Zolpidem and zaleplon (imidazopydridine and pyrazolopyrimidine agents, respectively) act as agonists at the benzodiazepine receptor component of the γ-aminobutyric receptor complex.^{21 - 22} They are rapidly absorbed, do not have active metabolites, and are well-tolerated with low risk for tolerance and a low abuse potential. Zolpidem has been extensively studied, with an excellent therapeutic profile with nightly use for up to 6 months, the longest duration studied.^{21 - 22} At our centers, patients with chronic insomnia are usually well-controlled during nightly zolpidem treatment of more than 6 months' duration (C.H.S., unpublished data, 2003). The usual dose is 5 to 10 mg at bedtime. Zaleplon is an ultrashort-acting agent that is effective in promptly restoring sleep in patients with problematic nocturnal awakenings. The usual dose is 5 to 10 mg. Benzodiazepine hypnotics can also be safely and effectively used for short-term therapy,⁹ and possibly also for long-term nightly use in carefully diagnosed, refractory, chronic insomnia patients,^{9 ,20} although systematic studies on long-term use have yet to be published. A referral to a sleep specialist is recommended for patients being considered for long-term treatment with benzodiazepines or related agents that at times can cause morning sedation, memory dysfunction, dosage tolerance, or misuse. Close physician monitoring is thus encouraged. The following can also be effective for short-term use and possibly long-term use in controlling insomnia: doxepin or amitriptyline (>10-50 mg); triimpramine (25-100 mg); imipramine (>10-75 mg); and trazodone (>25-100 mg).

For patients with insomnia associated with depression, various pharmacologic strategies exist² : sedating antidepressants; combination of sedating and nonsedating antidepressants; benzodiazepine or related hypnotic in mild-moderate depression treated with psychotherapy; combination of an antidepressant with a benzodiazepine or related hypnotic. Cognitive-behavioral therapy, which requires specially trained clinicians, can be quite effective in treating chronic insomnia.²³ This therapy is directed at altering dysfunctional beliefs about sleep that perpetuate insomnia.^{2 ,23} Sleep restriction and sleep consolidation therapy aim to minimize the amount of wakefulness in bed by limiting the total time in bed.² This therapy requires a high level of patient motivation, because the patient must stay out of the bedroom until a late hour (3 AM) and then go to bed 15 minutes earlier on successive nights, until the target bedtime is achieved.²

Over-the-counter drugs containing sedating antihistamines (diphenhydramine) are widely used by the public for insomnia. However, the efficacy of these agents in treating insomnia has not been established. Although US patients have shown a growing interest in alternative therapies,²⁴ there is currently insufficient scientific knowledge on the efficacy and safety of herbal treatments of insomnia.²⁵ Valerian and kava are probably the most commonly promoted herbal remedies of insomnia in the United States, with the former being more rigorously evaluated. A recent randomized, double-blind study of 202 patients with nonorganic insomnia found that after 6 weeks of treatment, valerian was as effective as the benzodiazepine oxazepam.²⁶ Hepatotoxicity, cardiotoxicity, and delirium occur sporadically with use of valerian; dermatotoxicity and interactions with sedatives and alcohol may occur with use of kava.

In circadian rhythm sleep disorders, insomnia results from a mismatch between the endogenous sleep and alertness rhythm and the desired (or required) time for sleep and wake.²⁷ The mismatch can result from external challenges to the circadian system, such as night-shift work and jet travel; vulnerabilities in the endogenous circadian mechanisms, such as having a circadian clock with an overly short intrinsic period (as in familial advanced sleep-phase syndrome); or a lack of environmental time cues, as in the case of individuals who are blind and whose rhythms free-run on a non–24-hour cycle.

The circadian clock is located in the suprachiasmatic nucleus of the hypothalamus, and its intrinsic period generated by a gene-protein feedback loop in humans is slightly longer than 24 hours; consequently, precise synchronization to a 24-hour day (entrainment) depends on input from the environment, especially the solar light and dark cycle. The effect of light exposure on circadian rhythms is critically dependent on its timing: in the morning, light shifts the clock earlier but, in the evening, it shifts the clock later. Nonphotic time cues (scheduled sleep and activity) may have some influence on the clock, but the effects are weak compared with light exposure.

During the day, the circadian clock generates an alerting signal that counteracts the normal accumulation of sleep drive related to duration of time awake, and thereby maintains a relative balance toward wakefulness. As bedtime approaches, the circadian alerting process recedes, allowing for sleep and the dissipation of sleep drive. In circadian rhythm sleep disorders, the circadian alerting process is misaligned and overlaps the desired time for sleep, resulting in insomnia.

Jet Lag. After rapid travel across time zones, endogenous circadian rhythms become out of phase with local time. Symptoms include insomnia, daytime sleepiness, and gastrointestinal disturbances that gradually resolve as the internal body clock catches up to local time and circadian harmony is restored. Besides circadian desynchrony, other contributors to jet lag include poor sleep due to uncomfortable airline seats, disruption by other passengers, liberal use of alcohol and caffeine, and a shortened sleep opportunity. After arrival, insomnia can persist and be exacerbated by sleeping in a novel environment.

Night-Shift Work. A more persistent form of circadian desynchrony underlies the insomnia of night-shift workers. The nonadapted night worker must sleep when the circadian pacemaker is promoting wakefulness and must stay awake and alert when the circadian pacemaker is signaling sleep. Sleep during the day is typically foreshortened, and after a few days, a cumulative sleep debt may build that compounds nighttime sleepiness. Some night workers are able to synchronize their internal rhythms to their work schedules, but many never do. Bright light exposure on the job may promote adaptation by shifting circadian rhythms but sunlight on the commute home from work may block it.

Delayed and Advanced Sleep Phase Syndromes. Patients with delayed sleep phase syndrome (DSPS) are extreme night owls who prefer to stay awake late into the night and wake up at midday, a schedule that conflicts with employment or school obligations. Many adolescents have a tendency toward DSPS, even if they do not meet strict criteria for the syndrome. Delayed sleep phase syndrome may result from an intrinsic circadian period that is significantly longer than 24 hours, making entrainment to a conventional schedule very difficult.

Advanced sleep phase syndrome is rare. However, a tendency toward advanced sleep phase syndrome is common in older people who doze off in the evenings and awaken prematurely. The syndrome may be related to an intrinsic circadian period that is significantly shorter than 24 hours.

Other kinds of insomnia include Sunday night insomnia that results from staying up late on the preceding nights, thereby delaying the peak of circadian alertness so that it coincides with bedtime. Also, insomnia may occur during the winter months, because morning light is insufficient to maintain normal entrainment.

A sleep diary can provide a clear picture of the temporal patterns of sleep. The Horne-Ostberg scale²⁸ assesses the tendency for people to prefer the morning hours (larks) vs the evening hours (owls). Actigraphy is invaluable for helping diagnose circadian disorders.

Treatments involve resetting the circadian clock so that it is more congruent with the desired or required sleep-wake schedule. Bright light exposure in the morning can shift circadian rhythms earlier and has been shown to be effective for the treatment of DSPS.²⁹ The treatment can be as simple as having the person go for a walk outside in the morning (even cloudy days can provide sufficient sunlight), although artificial bright light fixtures may be necessary in the winter. Bright light in the evening shifts rhythms later and is effective for treating advanced sleep phase syndrome and possibly also elderly people with insomnia who have early morning awakening based on circadian mechanisms. Dark goggles worn on the morning commute from work have been shown to improve adaptation of night workers.

Melatonin is a hormone secreted at night by the pineal gland that can shift the circadian pacemaker in an opposite direction from light (considered a darkness signal). When administered in the evening, it shifts rhythms earlier but, in the morning, shifts rhythms later. It is important to take melatonin at the appropriate time to promote the desired clock-resetting effect. In clinical trials, melatonin has been shown to accelerate adaptation to night work and to alleviate DSPS and jet lag.³⁰ The commonly available doses of 0.5 and 3 mg appear to be safe. Effective strategies exist for scheduling bright light exposure and for using melatonin to induce circadian adaptation in permanent night-shift workers.³¹

It is difficult to induce a large circadian phase shift in 1 or 2 cycles; rather, persistent small adjustments are more likely to succeed. For example, patients with DSPS can be treated with gradual advances in their sleep times, from 15 to 30 minutes every 2 to 3 days. The schedule is reinforced with bright light exposure in the morning, melatonin in the evening, and if necessary, sleeping medication at night.

Intermittent use of hypnotic medications can benefit a night worker who has difficulty sleeping during the day; conversely, caffeine can promote alertness at night. Overriding the clock may be a particularly logical strategy for a brief run of night-shift work (1 or 2 nights) in which circadian resetting would either be impossible or undesirable. This strategy can be also be used for jet lag until the circadian system is aligned to local time.