Pathophysiology

A widely accepted model of chronic insomnia suggests that it is a function of predisposing, precipitating, and perpetuating factors. Little is known about predisposing biologic or psychological factors, although it does seem clear that certain persons are at greater risk than others for the development of a chronic insomnia problem. Precipitating factors (which are sometimes referred to as causes of chronic insomnia) are identified in Box 227-1 and are discussed in greater detail later.

A unifying concept in the pathophysiology of chronic insomnia is that of hyperarousal.⁵ Data indicate that patients with this condition exhibit evidence of both physiologic and cognitive hyperarousal, in the form of increased 24-hour metabolic rate, increased temperature, muscle tension, sleep electroencephalogram frequency, overactivity of the hypothalamic-pituitary-adrenal axis, and cognitive activity. It remains unclear how this hyperarousal develops, although preliminary data suggest that it is, at least in part, acquired and is amenable to change with therapeutic interventions such as cognitive behavioral treatment.

Clinical Presentation

Psychiatric disorders, especially major depression, are the most common precipitating factors. Generalized anxiety, panic, and post-traumatic stress disorders are also associated with elevated rates of insomnia. Substance abuse or dependence, including alcohol, sedative-hypnotics, stimulants, and opiates, frequently manifests with insomnia, which may persist even after discontinuation of the substance. Excessive use of caffeine or even moderate use later in the day may also be problematic.

Circadian disorders, especially shift work and delayed sleep-wake phase disorder, are commonly associated with sleep complaints. Significant percentages of night shift workers experience abnormal sleep, with reduced total sleep times and poor quality of sleep. This pattern does not tend to improve during long periods of night work for most shift workers. As a result of circadian misalignment and sleep disturbances, shift workers are at increased risk for a number of medical disorders (ulcer disease, breast cancer among female shift workers, and cardiovascular disease) as well as accidents. Delayed sleep-wake phase disorder occurs most commonly in adolescents and younger adults and is characterized by an inability to sleep at normal clock times, with normal sleep onset occurring late (e.g., 4 AM), and subsequent inability to arise at conventional times (e.g., noon awakening). Sleep is otherwise restorative and normal, but the schedule is clearly inconsistent with meeting of normal school or work times. Advanced sleep-wake phase disorder is a less common circadian rhythm disorder, with normal sleep quantity and quality occurring early in the 24-hour day (e.g., 7 PM to 3 AM). It appears to be most common in older adults.

Medical conditions and medications may contribute to sleep disturbance. Among the most common are those associated with nocturnal pain, chronic lung disease, end-stage organ failure, endocrine disorders and other metabolic conditions, and especially neurodegenerative diseases. Likewise, many medications may aggravate sleep, most notably steroids, methylxanthines, some antihypertensives, stimulants, and certain antidepressant medications.

Other physiologic sleep disorders may result in an insomnia problem. The patient with restless legs syndrome (RLS) reports distressing, “creepy-crawly” sensations in the legs or, less commonly, arms. The sensation is associated with an irresistible urge to move the extremities. The sensations may interfere with sleep onset. RLS is often associated with periodic limb movements (PLMs), which are characterized by repetitive, periodic (every 20 to 40 seconds) limb movements, often resulting in arousals that the sleeper is unaware of (much as in obstructive sleep apnea [OSA]). RLS is discussed in greater detail in the section on movement disorders.

Although OSA is most often associated with complaints of daytime sleepiness rather than with insomnia, these patients may have clinically significant complaints of insomnia. This association may be more prevalent among women with OSA. Therefore OSA must also be considered in the differential diagnosis, particularly in obese patients and those with heavy snoring.

The essential features of chronic insomnia according to the ICSD-3 are frequent and persistent difficulty initiating or maintaining sleep with a daytime consequence. An important subtype of chronic insomnia is psychophysiologic insomnia (PPI), a conditioned arousal in response to efforts to sleep and negative expectations regarding the ability to sleep. Individuals with PPI may be able to sleep better when they are not trying to fall asleep or in settings other than their own bedroom. Symptoms may include difficulty getting to sleep as well as trouble returning to sleep after awakening. This type of insomnia exists commonly as a disorder in its own right. However, the hyperarousal and negative conditioning that occur in this disorder are frequent complicating factors in insomnia that is associated with the numerous precipitating factors described earlier. Often, when an initial precipitating factor (e.g., a major depression, acute stress, or medical illness) resolves, it is these conditioned psychophysiologic elements that serve as the perpetuating factors noted earlier in this chapter.

Diagnostics

The essential element in the evaluation of an insomnia complaint is the history. The nature of the onset, course, complications, and treatments of the condition must be elicited in detail. Sleep-wake schedule, including napping, is critical to assessment. Sleep logs, usually conducted for 1 or 2 weeks, can be a helpful adjunct to history. The log should contain the following information for each night: time of getting into bed, time lights are actually turned out (e.g., after television, reading), estimate of sleep latency (time to fall asleep after lights out), estimate of the number of awakenings and total awake time across the night, time of final awakening, and time of actual arising. Evidence of other sleep-related symptoms (e.g., snoring and observed pauses in breathing, limb movement or restless legs, nightmares, behavioral disturbances, headaches, pain, gastroesophageal reflux) must be sought from the patient and, whenever possible, the bed partner. Daytime consequences, particularly evidence of significant sleepiness, should be assessed. Medical, neurologic, and psychiatric evaluations as well as pertinent physical examination and appropriate laboratory procedures are essential.

Polysomnography (PSG), overnight sleep recording, contributes little to the diagnosis of most insomnia presentations and is usually reserved for those cases in which demonstrable physiologic disturbances are suspected, typically breathing disorders, hypersomnias, and some parasomnias. PSG may also be appropriate for patients with treatment-refractory insomnia.

Differential Diagnosis