Premature aging

Sleep and mood disorders interact on many levels from epidemiology to clinical presentation. Older individuals may be at particular risk for disturbances of sleep, namely insomnia, as well as disturbances in mood, such as major depression. In some ways, the sleep changes typical of depression can be seen as a form of "premature aging" of sleep, which may help to explain why the interaction between sleep and mood becomes especially important in older adults. This article will discuss the clinical epidemiology of sleep and depression; laboratory findings relevant to sleep and depression in older adults; and treatment implications.

Clinical epidemiology

Older adults report several types of sleep changes, including earlier sleep hours, increased napping and sleepiness, and increases in specific sleep disorders, such as sleep apnea and periodic limb movement disorder. (1) However, insomnia is the most common sleep complaint in older adults. The symptom of insomnia is defined as a complaint of difficulty falling asleep, staying asleep, or sleep that is non-restorative. Clinically significant insomnia, which can be thought of as the clinical disorder of insomnia, includes the insomnia symptom accompanied by significant distress or impairment that lasts for longer than 1 month. (2) Epidemiological studies have confirmed a high prevalence of insomnia in older adults. When considering simply the complaint of insomnia, approximately 20 to 40% of older adults report at least one symptom (ie, difficulty falling asleep, difficulty staying asleep, or waking and being unable to fall back asleep). (3-7) However, these prevalence figures probably overestimate the number of individuals with clinically significant insomnia (ie, persistent insomnia that also causes distress or impairment). When considering this more stringent definition, approximately 12 to 20% of older adults report what could be considered the clinical disorder of insomnia. (3,8) Studies conducted in general practice settings reveal the same general trends; the complaint of insomnia increases as a function of age, with a prevalence of 25 to 30%. (9)

These studies reveal several consistent risk factors for insomnia. The first risk factor is age. However, the association between age and insomnia greatly diminishes, or even disappears, when other risk factors are taken into account. The second risk factor is gender; the rates of insomnia in women are typically 20 to 50% higher than in men. Third, previous insomnia is a risk factor for current insomnia; thus insomnia tends to be a persistent problem. Whereas the prevalence and incidence of insomnia increase with age, remission rates decrease with age. This means that older adults are particularly prone to chronic insomnia. Of those with insomnia at one point, approximately 50 to 75% have persistent problems over the following 2 to 3 years. (4,5) Fourth, chronic health conditions are associated with insomnia. In particular, medical conditions that cause chronic pain (eg, arthritis), limited mobility (eg, Parkinson's disease), or difficulty breathing (eg, chronic obstructive pulmonary disease) are commonly associated with insomnia. The number of medications taken is also related to insomnia, although the number may simply be a surrogate measure for the medical conditions they treat. Fifth, prevalence of insomnia is inversely related to socioeconomic status.

Perhaps most importantly, several studies have shown that depression is a powerful risk factor for insomnia. Katz and McHorney (10) reported depression as a risk factor associated with mild and severe insomnia. Although chronic health conditions, such as congestive heart failure, chronic obstructive pulmonary disease, hip problems, and prostate problems, were all significantly associated with insomnia, major depressive disorder was about 2 to 3 times as potent a risk factor. Aside from insomnia, depression is also a risk factor for other sleep symptoms, such as severe daytime sleepiness. (11) Surveys of individuals with chronic insomnia confirm that insomnia related to major depression is the most common single diagnosis. (12,13)

It had been thought that the prevalence of depression increased with age. However, it is now recognized that older studies were biased because many depressive symptoms were attributed to concurrent medical illnesses. Recent estimates suggest that the prevalence of all depressive disorders in older adults is approximately 10 to 15%, and the prevalence of major depression is about 2%, (14) comparable to that for all adults over age 18. (15) Just as insomnia has risk factors, so too does depression, and these risk factors often overlap with those of insomnia. For instance, late-life depression is more common in women; in those with alcohol and substance abuse history; in those with multiple medications and medical disorders; and in those with socioeconomic stressors, such as bereavement, institutionalization, or other losses. Specific medical disorders that increase the risk for depression include stroke and other forms of cerebrovascular disease, coronary heart disease, Alzheimer's disease and other forms of dementia, and cancer. It is worth noting that some risk factors may be bi-directional. Patients with depression are in turn at greater risk for cardiovascular disease, (16) as well as cognitive impairment. (17,18)

Depression in older adults has significant consequences. In addition to well-recognized reductions in quality of life and functional status, late-life depression signficiantly increases the risk for suicide. According to the National Vital Statistics report in 1997, persons age 65 and older comprise 13% of the U.S. population, but 19% of completed suicides. The highest risk group is men age [greater than or equal] 85, who have a suicide rate of 64.9/100,000, compared with the overall U.S. rate of 10.6/100,000.

Finally, several studies have shown that insomnia at one time point is a risk factor for developing depression at a later time point. (8,19-23) This finding has been demonstrated in younger and older adults, and over follow-up intervals of 1 to 35 years. The risk relationship holds even after accounting for the presence of depression at baseline. For instance, Mallon et al found that insomnia was as strong a risk factor for depression as initial depression itselfduring a 12-year follow-up in a sample of older adults. (24)

Relevant laboratory findings

Laboratory sleep studies (polysomnography [PSG]) demonstrate four basic types of sleep disturbance in patients with depression (PSG figures can be found at www.geri.com):

1. Impaired sleep continuity. Sleep continuity refers to the overall balance of sleep and wakefulness during the night; its symptoms define insomnia. Impaired sleep continuity includes prolonged sleep latency (ie, the time it takes to achieve consolidated sleep), frequent awakenings, prolonged awakenings, and/or awakening early in the morning and being unable to fall asleep ("early morning awakening"). Because aging itself is associated with earlier timing of sleep and specific difficulty maintaining sleep in the latter half of the sleep period, (25,26) early morning awakening is often the prominent feature of sleep disturbance in older depressed patients.

2. Changes in rapid eye movement (REM) sleep. Patients with depression usually have an increased amount of REM sleep compared with non-depressed patients. In older adults, increased REM sleep amount distinguishes depressed patients from those with dementia, (27,28) who show reductions in REM sleep proportional to the degree of cognitive impairment. (29) In addition, depressed patients often show more physiologic activity during REM sleep as indicated by the number of actual eye movements or "REM density."

3. Non-rapid eye movement (NREM) sleep abnormalities. The most prominent is reduced "deep" sleep, designated as Stages 3 and 4. These sleep stages are characterized by large amounts of slow frequency EEG waves, known as delta activity. The reduction in NREM Stage 3/4 sleep in depressed patients mirrors the aging process, which is also associated with a reduction in NREM sleep.

4. Changes in timing of sleep stages. Normal sleep begins with lighter stages of NREM sleep, progressing to deeper NREM and then into REM sleep. NREM and REM sleep alternate approximately every 90-100 minutes throughout the night. In depressed patients, an increase in REM sleep "pressure" and reduction in deep NREM sleep result in an earlier than usual occurrence of REM during the sleep period, referred to as reduced REM latency. Reduced REM latency is yet another example of depression reflecting a normal age-related change in sleep.

Sleep characteristics, such as sleep efficiency, REM latency, and REM density, are consistently more abnormal in those with severe depression than in healthy individuals. (30) However, many of the sleep changes in depression are also seen in other psychiatric conditions, such as anxiety or schizophrenia. However, the increase in REM sleep and increase in REM density are relatively specific for depression. (31)

A number of other laboratory changes have been noted in patients with depression. These include: decreased secretion of growth hormone during early NREM sleep; increased cortisol secretion in the second half of the night; and a blunted circadian rhythm in body temperature. (32) Recent studies have also shown abnormalities of cortisol in patients with "primary" insomnia, although the increase in ccortisol tends to be in the first rather than the second part of the night. (33,34)

Patients with depression show consistent changes in sleep physiology, and these changes increase with age. In fact, these changes represent some of the most consistent biological markers of depression, and further substantiate the link between sleep, depression, and aging.

Treatment implications

Given that poor sleep is a risk factor for the development of depression and for poor outcomes in older adults with depression, it seems plausible that improving sleep may improve depression outcomes. Although definitive support for this hypothesis is lacking, there is little doubt that improving sleep quality improves depressed patients' quality of life. Treatment strategies include:

1. Standard antidepressant agents or psychotherapy. In general, when depression improves, insomnia improves as well. The first step in treating depression-related insomnia should therefore be adequate treatment of the depression. In many cases, no specific treatment will be needed for the sleep problem. Improvements in sleep have been demonstrated during the course of standard depression treatments, such as selective serotonin reuptake inhibitors or other antidepressants, and psychotherapy such as interpersonal psychotherapy or cognitive behavior therapy. (35,36) Table 1 lists common antidepressant drugs and their effects on sleep.

2. Sedating antidepressants. Some patients may benefit from more sedating antidepressants, such as nefazodone, mirtazapine, or sedating tricylcic antidepressants, which can treat both depression and insomnia. However, the degree of sedation may be too extreme for some patients to tolerate, and use of a single agent makes it difficult to separately treat insomnia and depression when the symptoms follow different time courses.

3. Standard antidepressant plus benzodiazepine receptor agonist (BzRA). Several studies show that concurrent treatment with a benzodiazepine for sleep disturbance does not delay the antidepressant response and may facilitate adherence with treatment even in older adults. (37) Concerns about benzodiazepines causing depression seem unwarranted in this clinical situation. However, side effects of benzodiazepines such as sedation, increased risk of falls, and respiratory depression in those with severe pulmonary disease must be considered, particularly in older adults. In addition, patients with substance use histories should be treated cautiously, if at all, with BzRAs. Selection of BzRAs with shorter half-lives (eg, zolpidem, zaleplon) is usually more appropriate in older patients. Table 2 which can be found on the Geriatrics website (www.geri.com) lists characteristics of common hypnotic drugs.

4. Standard antidepressant plus trazodone. Trazodone has become a widely used agent for treatment of insomnia. Although no studies have been reported in older adults, treatment with standard antidepressants showed improved insomnia symptoms in younger adults when low-dose trazodone was used as an adjunctive treatment. (38)

5. Behavioral treatments of insomnia. Numerous studies have documented the efficacy of various behavioral treatments for insomnia in younger and older adults, (39) although few studies have been conducted specifically in depressed patients. These treatments can be used in combination with pharmacotherapy. Behavioral treatments differ in their specific practices, but they share a few general principles that can be used with most insomnia patients. These include:

* Get out of bed at the same time in the morning, regardless of how much you have slept the night before.

* Cut down time in bed to match the amount of time you can actually sleep.

* Do not go to bed until you are actually sleepy.

* Do not stay in bed for long periods if you cannot sleep. Get up, go somewhere else, keep the lights low, and return to bed only when you are about to fall asleep.

* Avoid caffeine and alcohol.

Behavioral changes require practice over days or weeks to demonstrate their effects, however, they can have long-lasting beneficial effects.

Finally, just as it is worth treating insomnia in patients who have depression, it is mandatory to assess the presence of depression in older adults presenting with insomnia. Depression is consistently the most common cause of insomnia in both clinical and epidemiological studies.

Summary

Insomnia is related to worse outcomes in patients with depression, as judged by resolution of a current episode or recurrence of a new episode.

Insomnia and depression are prevalent conditions in older adults. Increasing age is a risk factor for insomnia, depression, and adverse outcomes associated with these conditions. Furthermore, insomnia tends to become a more chronic problem with age. Sleep laboratory studies show consistent sleep changes in patients with depression, and these changes are even more marked in older adults. The clinical relevance of these observations is that poor sleep is a risk factor for poor outcome in depression, and conversely, depression is the most common cause of chronic insomnia. Given the important effects of insomnia and depression on quality of life and other medical problems, physicians should ask older patients these questions about their sleep:

* Do you have trouble falling asleep or staying asleep at night? Does this cause problems for you during the day?

* Do you feel extremely sleepy during the day or have trouble staying awake?

* Have you been feeling sad or anxious? Have you had trouble enjoying things?

Given the important effects of insomnia and depression on quality of life and other medical problems, treatment of sleep disturbances in older depressed patients may improve outcomes and certainly improves quality of life.

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This material was originally presented at the Congress of Sleep, Health, and Aging, sponsored by the National Sleep Foundation March 30-31, 2003, in Washington, DC.

Dr. Buysse is associate professor of psychiatry, Sleep and Chronobiology Program, Department of Psychiatry, University of Pittsburgh School of Medicine. Dr. Buysse is supported by NIH grants MH24652, AG20677, AG15138, MH30915.

Disclosure: Dr. Buysse is a paid consultant to the following: Sanofi-Syntholabo, Eli Lilly and Co., Pfizer, Sepracor, Neurocrine Biosciences, Cephalon, and Takeda Pharmaceuticals.

Sponsorship: This is the second article in a 3-part series on sleep disorders in geriatric patients sponsored by an unrestricted educational grant from Sanofi-Syntholabo.

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