Medical Illness, Medications, and Sleep in Older Adults
Sleep complaints in older adults are often associated with comorbid illnesses or medications rather than to aging per se (Figure 3). Chronic diseases become more prevalent as patients age, and it is not uncommon for older patients to have multiple concurrent medical conditions. Studies have found that patients with multiple health problems are more likely to have sleep difficulties as well, and that their sleep quality decreases with an increasing number of medical conditions. The 2003 “Sleep in America” survey found that 36% of people age 65 years and older with no comorbid illnesses had sleep problems, 52% with one to three comorbidities had sleep disturbances, and 69% of those with four or more comorbidities had disturbed sleep. The self-perceived quality of these respondents’ sleep was inversely proportional to the number of comorbidities they had.1
The term secondary insomnia is frequently used to denote the link between medical diagnoses and the accompanying sleep change. A number of chronic conditions, and the medications used to treat them, are associated with disturbed sleep, including chronic pain conditions, cardiovascular disease, pulmonary disease, endocrine and renal diseases, gastrointestinal conditions, neurologic diseases, and genitourinary conditions. These conditions are associated with varying degrees and types of sleep problems (Figure 4).2-7
The 2005 National Institutes of Health State-of-the-Science Conference on Insomnia recognized this relationship and has suggested that the term comorbid insomnia be incorporated into the lexicon of practitioners.8 The precise relationship between illness and the changes in brain function that result in insomnia remain uncertain. Frequently, health problems produce symptoms of discomfort or emotional distress that lead to neural activation in systems that regulate arousal and sleep. The psychological factors of hyperarousal, stress response, predisposing personality traits, and maladaptive attitudes all contribute to insomnia in the setting of chronic illness. There is concern that once sleep changes are attributed to a physical or psychological illness, they may be undertreated. Likewise, there is an evidence-based appreciation for how sleep impairment exacerbates many chronic diseases and can lead to greater morbidity and mortality. To improve quality of life and optimize patient care outcomes, treatment of this form of secondary insomnia remains paramount.
Conditions that Disturb Sleep
Arthritis is a leading cause of disability in the United States, affecting an estimated 43 million Americans.9 Evidence suggests that as many as 60% of those with arthritis experience pain during the night. The relationship between pain and sleep is complex; pain can disrupt sleep, and poor sleep may increase pain intensity. Patients with arthritis have been observed to have problems initiating sleep (31%), problems maintaining sleep (81%), and a tendency to awaken early in the morning (51%). Poor sleep in patients with osteoarthritis correlates with increased perceived pain, decreased self-rated health, poor functional status, and depression. Patients with rheumatoid arthritis have a high prevalence of RLS (25%).2,10,11 Furthermore, individuals with self-reported arthritis-related sleep disruption are more likely then those without sleep disturbance to pursue multiple sources of self-care and medical care.12
Gastroesophageal reflux disease (GERD) is quite common with over 44% of the general population having monthly symptoms, and 7% having daily symptoms.13 The relationship between disturbed sleep and GERD is bidirectional: sleeping increases the likelihood of reflux, and reflux episodes often awaken the patient.14-17 Patients with nighttime acid reflux may underestimate the degree of sleep disruption that occurs when objective measurements of pH and electroencephalogram (EEG) arousal are compared to patient recollection the next morning.14
Reviewing the patient history for nocturnal cough or wheezing as a surrogate for reflux is also important, since not all patients with overnight reflux will experience classic chest pain, but their sleep may be disrupted nevertheless. Considerable anecdotal evidence supports that patients who have been successfully treated for heartburn complaints will spontaneously report that they are sleeping better. Finally, a mechanical link between the phrenoesophageal ligament and the lower esophageal sphincter may explain the coexistence of sleep apnea and reflux.18,19
Many relationships between cardiac disease and sleep disturbance exist. A well-described circadian peak in myo-cardial ischemia or infarction occurs between 4:00 am and 8:00 am. Chronic problems with falling asleep correlate with an increased risk of death from coronary artery disease.5 The classic sleep maintenance disturbance associated with congestive heart failure includes orthopnea, paroxysmal nocturnal dyspnea, and occult sleep apnea. More than 50% of patients with moderate-to-severe congestive heart failure experience Cheyne-Stokes respiration, increased sleep fragmentation, and an increase in daytime sleepiness.20,21 More severe nighttime periodic breathing occurring in heart failure correlates with worse prognosis and increased cardiac death.22,23 Finally, coronary artery bypass surgery is associated with protracted sleep disturbance up to two years following the procedure.20
Approximately 25% of patients with chronic obstructive pulmonary disease complain of excessive sleepiness. Hypoxemia, which is common in rapid eye movement (REM) sleep, correlates with an increase in arousal and excessive daytime sleepiness. While the use of oxygen therapy frequently corrects the underlying hypoxemia, it does not appear to improve sleep quality.6,24 This suggests that other mechanisms, such as cough, impaired airflow, excessive respiratory secretions, or dyspnea, may be contributing to the observed sleep disruption. The use of ipratropium bromide inhaler improves sleep quality and duration, presumably via improved airflow.25
Diabetic patients manifest a number of adverse sleep changes. The severity of sleep disruption directly correlates with the severity and level of control of the disease. One-third of patients with diabetes have problems with sleep fragmentation. Causes for this include nocturia, leg cramps, leg pain, and cough. Likewise, patients with diabetes have an increased prevalence of both restless legs syndrome (RLS) and periodic limb movements of sleep. Patients with diabetes are also at increased risk for obstructive sleep apnea (OSA), and recent studies demonstrate that the sleep deprivation associated with sleep-disordered breathing contributes to increased insulin resistance, thereby worsening glycemic control.7,26,27
Fifty-seven percent of patients with end-stage renal disease report sleep maintenance problems, and 55% report early morning awakening. There are marked abnormalities seen in the sleep EEGs of patients with chronic kidney disease. This likely reflects the impact of uremia and other metabolic derangements on brain function during sleep. Patients on hemodialysis have a higher prevalence of OSA (which improves following dialysis), RLS, periodic limb movements, early insomnia, and excessive daytime sleepiness.28-30 With the treatment of anemia of kidney disease with erythropoietin, sleep quality has been documented to improve. This appears to correspond to reduced numbers of periodic limb movements.
Medications that Disturb Sleep
A multitude of over-the-counter (OTC) and prescription medications are known to influence the sleep-wake cycle. Their adverse effects are diverse but can be broadly categorized as those that are activating or stimulating to the brain, those that interfere with sleep physiology, those that directly exacerbate primary sleep disorders, and those that are overly sedating and thus induce increased daytime sleep. The practitioner should be sensitized to consider how individual therapies or drug–drug interactions frequently can influence sleep quality. It is especially important to avoid using hypnotics as agents to manage the adverse sleep effects of other medications, unless other alternatives have been exhausted.
Medications that disturb sleep via central nervous system activation include OTC decongestants; OTC drugs that contain caffeine, such as extra-strength agents for headache; beta-agonist inhalants or oral formulations; corticosteroids; and selective serotonin reuptake inhibitors, which have been shown to reduce sleep efficiency, delay sleep onset, and increase the number of nighttime awakenings. Drugs that disturb sleep in specific ways include supratherapeutic hypoglycemic agents; nicotine; alcohol; diuretics; short-half-life hypnotics, which disrupt sleep continuity; antidepressants; lithium; and antipsychotic medications, which exacerbate RLS and periodic limb movements (also worsened by withdrawal from alcohol and benzodiazepines). Additionally, beta-blockers depress melatonin secretion.
Optimizing Sleep for Patients with Comorbidities
A good sleep history is of primary importance in the effective treatment of sleep disturbance in patients with comorbid illness. When clinicians recognize how common medical problems affect sleep, they may choose a very different first-line therapy. For best outcomes, the underlying medical problems should be optimally managed, and any sleep-disruptive medications that can be changed should be adjusted or replaced. Sometimes targeted medical therapies, such as an analgesic for pain or intervention for anemia, may serve to be the best sleep aids. In addition, adjunctive behavioral and pharmacologic approaches that are applicable for other forms of insomnia should be considered if a sleep problem persists. It is essential to treat patients with comorbid insomnia with a holistic approach that addresses the underlying illness, as well as incorporates the standard of care for managing all insomnia.