Insomnia in the Elderly: A Review

Abstract

Background:

Insomnia remains one of the most common sleep disorders encountered in the geriatric clinic population, frequently characterized by the subjective complaint of difficulty falling or maintaining sleep, or nonrestorative sleep, producing significant daytime symptoms including difficulty concentrating and mood disturbances.

Methods:

A search of the literature was conducted to review the epidemiology, definition, and age-related changes in sleep, as well as factors contributing to late-life insomnia and scales utilized for the assessment of insomnia in older people. The aim is to summarize recent diagnostic guidelines and both nonpharmacological and pharmacological strategies for the management of insomnia in the older population.

Results:

Insomnia remains a clinical diagnosis. There are several demographic, psychosocial, biologic, and behavioral factors that can contribute to late-life insomnia. Older adults are at higher risk for the medical and psychiatric effects of insomnia.

Conclusions:

The most important aspect in evaluation of insomnia is detailed history taking and thorough physical examination. Nonpharmacological treatment options have favorable and enduring benefits compared to pharmacological therapy.

Citation:

Patel D, Steinberg J, Patel P. Insomnia in the elderly: a review. J Clin Sleep Med. 2018;14(6):1017–1024.

SCOPE OF THE PROBLEM

The population of older adults continues to expand rapidly from the current 205 million persons aged 60 years or older, to a projected 2 billion by 2050.¹ One of the most common sleep disturbances in the older population is insomnia.^2–4 As many as 50% of older adults complain about difficulty initiating or maintaining sleep.⁵ Prevalence of insomnia is higher in older individuals than in the younger population.⁶ The overall prevalence of insomnia symptoms ranges from 30% to 48% in the elderly,^5,7,8 whereas the prevalence of insomnia disorder ranges from 12% to 20%.⁹ Insomnia is often classified by the predominant symptom of either difficulty in sleep onset or sleep maintenance. Sleep maintenance symptoms are most prevalent among individuals with insomnia (50% to 70%), followed by difficulty in initiating sleep (35% to 60%) and nonrestorative sleep (20% to 25%).¹⁰ A study of 6,800 older adults (age 65 years or older) observed an incidence rate for insomnia symptoms of 5% per year,¹¹ with a yearly incidence of 7.97% at 1-year follow-up.¹² Approximately 50% of the patients with symptoms of insomnia will have a remission during the follow-up period, with higher remission rates among older males relative to females.^12,13

DEFINITION

Insomnia is broadly defined as dissatisfaction with sleep either qualitatively or quantitatively. This is usually associated with one or more of the following: (1) difficulty initiating sleep, (2) difficulty maintaining sleep, characterized by frequent awakenings or problems returning to sleep after awakenings, and (3) early-morning awakening with inability to return to sleep.¹⁴ The fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) emphasizes that a sleep disturbance causes clinically significant distress or functional impairment, and occurs at least 3 nights a week for at least 3 months despite adequate opportunity to sleep, whereas the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) requires at least 1 month of symptoms not explained by another sleep-wake disorder, illicit substance use, or coexisting medical and psychiatric disorders. The term “nonrestorative sleep” is no longer an accepted diagnostic symptom for the DSM-5; however, it still remains in the ICD-10 criteria. The pathophysiology of insomnia disorder induces a state of hyperarousal during sleep and wakefulness. Hyperarousal is manifested as an elevated whole-body metabolic rate during sleep and wakefulness, elevated cortisol and adrenocorticotropic hormone during the early sleep period, and reduced parasympathetic tone in heart rate variability.¹⁵ An important change with respect to diagnostic classifications was defined in the DSM-5 and the third edition of the International Classification of Sleep Disorders (ICSD-3). Insomnia in the ICSD-3 is defined as a complaint of trouble initiating or maintaining sleep that is associated with daytime consequences and is not attributable to environmental circumstances or inadequate opportunity to sleep. This replaces earlier categories of primary and secondary forms of insomnia in favor of a broad category for insomnia disorder when insomnia is comorbid with medical or psychiatric conditions.¹⁶ In a study of 6,800 elderly patients (older than 65 years), Foley et al. demonstrated that 93% have one or more comorbid conditions and other factors, most commonly depression, chronic pain, cancer, chronic obstructive pulmonary disease, cardiovascular diseases, medication use, and factors associated with aging (retirement, inactivity, or caregiving).^11,17–20 The increased prevalence of chronic conditions in later life may explain most insomnia symptoms in the older population; 1% to 7% of insomnia in later life occurs independently of chronic conditions.^20,21 Reduced mobility, retirement, and reduced social interaction are sources of sleep disturbances.^22–24 Caregiving may be responsible for ruminations and anxiety while trying to sleep. Women who are caregivers are found to have increased prevalence of sleep complaints.^18,25 Women are more often the primary caregivers for their children, parents, or partner, in addition to working outside of the home, affecting their total sleep time. Women are also more likely than men to complain of sleep problems and see a general practitioner for those complains.

FACTORS CAUSING INSOMNIA

Spielman and colleagues demonstrated a three-factor model for understanding the etiology and persistence of insomnia. This model identifies predisposing, precipitating, and perpetuating factors that combine to raise the likelihood of insomnia above the insomnia threshold.²⁶

Predisposing Factors

These include demographic, biologic, psychological, and social characteristics. Women older than 45 years are 1.7 times more likely to have insomnia than men.⁷ Those divorced, separated, or widowed are also more likely to have insomnia than married individuals.⁷ Lower levels of education or income may contribute to insomnia in some cases.^7,27 Smoking, alcohol use, and reduced physical activity are other factors associated with higher rates of insomnia in older adults.^7,18

Precipitating Factors

These factors generally include stressful life events or medical conditions that may disrupt sleep. Older adults with respiratory symptoms, physical disability, and fair to poor perceived health are at increased risk of insomnia.¹¹ Medications such as beta blockers, glucocorticoids, nonsteroidal anti-inflammatory drugs, decongestants, and antiandrogens may be one of the factors contributing to insomnia. Several studies have demonstrated that patients with depression and generalized anxiety disorder have higher rates of insomnia.^11,13,28

Perpetuating Factors

These factors often consist of behavioral or cognitive changes that arise as a result of acute insomnia. An acute episode of insomnia will not necessarily develop into chronic insomnia without these provoking behavioral and cognitive events. Examples include spending excessive time in bed, frequent naps, and conditioning (increased anxiety before sleep onset due to fear of spending another sleepless night). Nonpharmacological treatment options often target these perpetuating factors.

CHANGES IN SLEEP WITH AGING

Along with many physiologic changes seen with aging, signifi-cant changes also occur in sleep and circadian rhythm across the lifespan. Differentiated by waveforms on electroencephalogram and other physiologic signals, sleep is currently classified into four stages. The first three are non-rapid eye movement (NREM) stages: stage N1, N2, and N3 sleep. Rapid eye movement (REM) sleep occurs in the fourth stage, stage R sleep.²⁹ Stage N1 sleep is the lightest stage and it accounts for 18% of older adults' sleep time.³⁰ In stage N2 sleep, brain waves slow, body temperature begins to drop, and heart rate slows as sleep deepens, accounting for 48% of sleep time. Sleep further deepens in stage N3 sleep, characterized by very slow brain waves referred to as delta or slow wave sleep. This stage accounts for 16% of sleep.³⁰ Stage R sleep is “paradoxical sleep” because brain activity is similar to that in awake state with increased sympathetic tone characterized by rise in blood pressure and heart rate but with muscle atonia.³¹ Dreaming occurs in this stage of sleep and accounts for 18% of sleep time in older adults.³⁰ Total sleep time decreases considerably from 10 to 14 hours a night in the pediatric age range, to 6.5 to 8.5 hours a night as a young adult, then decreases at a slower rate in the older age range to 5 to 7 hours a night, and plateaus at about 60 years of age.³² The natural shortening of their total sleep time in some older adults may generate unrealistic expectations about sleep duration, producing anxiety that could cause or worsen insomnia.

Beginning in middle age, adults spend less time in slow wave sleep and REM sleep. Sleep efficiency continues to decrease past age 60 years. There is a prominent increase in wakefulness after sleep onset, but no change is observed in sleep latency.³² It is common for healthy older adults to exhibit a temporally advanced sleep phase (falling asleep early and waking up early).⁵ However, this may not be true for older adults with insomnia symptoms, who have a delayed circadian phase.³³ These individuals tend to have circadian dispersion and lack of synchronization compared to healthy subjects.³³ Early awakenings may result in frequent daytime naps, which further accentuates the problem of insomnia during the night.³⁴ Important time cues (zeitgebers) for circadian rhythm may erode as one ages; for example, elderly individuals may lack fixed work schedules or meal times due to retirement, which further contributes to insomnia. Healthy elderly individuals sleep as well as younger subjects according to an epidemio-logical study done by Ohayon.⁷ Research shows that older individuals may be more tolerant of sleep deprivation than younger ones. A study on psychomotor vigilance task performance after several nights of sleep deprivation in women aged 20 to 30 years compared to older women aged 55 to 65 years found younger women had more prominent impairments with sleep deprivation compared to an older age group.³⁵ The American Insomnia Survey of 10,094 individuals 18 years and older noted self-reported complaints of insomnia rates were lower in older adults (older than 65 years) compared to the younger group (18 to 64 years). This highlights the importance of approaching any complaint of insomnia in the older population with more vigilance.⁹

MORBIDIT Y ASSOCIATED WITH INSOMNIA

Insomnia is associated with significant morbidity if left untreated. The strongest level of evidence is for mental illness. Older individuals with insomnia have a 23% increase in risk of development of depression symptoms.³⁶ Several studies have documented an increased risk of depression in older patients with persistent insomnia.^37–39 A recent study noted 44% of older patients with persistent insomnia continued to have depression 6 months later as compared to only 16% of those without insomnia.³⁹ Insomnia and mental disorders such as depression and anxiety have a bidirectional relationship.⁴⁰ Additionally, insomnia also confers an increased risk of suicidal tedencies.⁴¹ A meta-analysis of insomnia symptoms and its association with heart disease, after adjusting for age and other cardiovascular risk factors, identified that risk ratios for heart disease from insomnia symptoms ranged from 1.47 to 3.90.⁴² Sleep loss and insomnia are associated with hypertension, myocardial infarction, and perhaps stroke.^43–46 In the Sleep Heart Health Study, a community-based cohort, adults (middle-aged and older) who reported 5 hours of sleep or less were 2.5 times more likely to have diabetes, compared with those who slept 7 to 8 hours per night.⁴⁷ Another study has also demonstrated that people with insomnia are at greater risk for metabolic syndrome.⁴⁸ Recent research also demonstrates that insomnia symptoms may lead to increased rates of cancer such as prostate cancer.⁴⁹ Long-term insomnia symptoms are also associated with greater risk of developing cognitive impairment.^50,51 A cross-sectional correlation between poor sleep quality and cortical atrophy has been shown in community-dwelling older adults.⁵² Insomnia is regarded as an independent risk factor for work disability, sick leave, and reduced work performance.⁵³ Economically driven analyses conclude that insomnia is associated with high direct and indirect costs for the health care system and society.⁵⁴

DIAGNOSIS

The evaluation and diagnosis of insomnia is a clinical one, based on a thorough clinical history of the sleep problems and relevant comorbidities obtained from the patients, their partners, and/or caregivers. Evaluation of insomnia symptoms presents challenges as they may occur as a primary disorder or result from other comorbid conditions. The clinician should evaluate the nature, frequency, evolution, and duration of symptoms, as well as the response to treatment. Using various sleep diaries and questionnaires, a thorough assessment of insomnia can be achieved. A Consensus Sleep Diary that includes detailed questions can assist in obtaining additional sleep history.⁵⁵ The temporal aspects of sleep (time at which a patient goes to bed, attempts at sleep, wake-up time, and final time out of bed), quantitative aspects (sleep onset latency, number and duration of awakenings, wakefulness after sleep onset, total sleep time), and qualitative aspects (subjective sleep quality, satisfaction) should be noted. Behavioral factors, such as the use of electronic devices before going to bed, should also be addressed because these can suppress bedtime melatonin production, adversely affecting circadian rhythm.⁵⁶ Environmental factors including bedroom temperature, light intensity, sound level, and sleep patterns of the partner should also be assessed. The clinician should also inquire about symptoms generated by other sleep disorders including obstructive sleep apnea (snoring, breathing pauses), restless leg syndrome (urge to move the extremities), parasomnias (unusual sleep behaviors), and circadian rhythm disorders (unusual sleep timings). Determining the use of alcohol, caffeinated drinks, cigarettes, and any other substance that can adversely affect the quality of sleep is also very important. An insomnia evaluation should also include a history and physical examination related to medical and psychiatric disorders that can exacerbate insomnia. Neurological disorders (stroke, migraine), chronic pain, endocrine disorders (hypothyroidism/hyperthyroidism), chronic obstructive pulmonary disease, asthma, gastroesophageal reflux, and congestive heart failure can lead to or worsen insomnia. The clinician should also ask about depression, bipolar disorder, and anxiety disorders. Medication use should be reviewed, as sedatives, antidepressants, antihypertensives, steroids, and antihistamines can interfere with sleep.

Modalities That Assist the Clinician in the Evaluation of Insomnia

Wrist Actigraphy

Wrist actigraphy, which monitors and stores movement data for up to 28 days, can be used to monitor treatment response and to screen for other circadian disorders.^57–59

Polysomnography

Polysomnography is not recommended for the evaluation for insomnia, but contributes to the evaluation of sleep apnea or parasomnias.⁶⁰

Insomnia Rating Scales

Numerous insomnia rating scales record symptoms and monitor the response to treatment.

The Insomnia Severity Index measures the subjective symptoms and negative outcomes of insomnia over the previous 2 weeks. On this scale, scores higher than 14 suggest “clinical insomnia.”⁶¹ The Pittsburgh Sleep Quality Index, a 19-item questionnaire, measures 7 domains of sleep over the prior month. Global scores higher than 5 indicate clinically significant sleep disturbances.⁶²

Imaging Studies

Daytime imaging studies are not needed for diagnosis of insomnia; however, if performed, MRI studies detect gray matter reduction in the frontal lobes of the brain^63–65 and reduced hippocampal volume.^66–68

TREATMENT

If left untreated, insomnia can have multiple medical and psychological consequences, emphasizing the importance of insomnia at any age. Treatment can be divided into nonpharmacological and pharmacological options.^16,24,25,69 Aging increases body fat, and reduces total body water and plasma proteins, resulting in increased drug elimination half-life and the potential risk of adverse effects. Older adults should therefore be treated with nonpharmacological options prior to pharmacological options.^16,70

Nonpharmacological

There are several nonpharmacological options for the treatment of insomnia, including relaxation techniques, improving sleep hygiene, and cognitive behavioral therapy. These options are effective in managing insomnia for extended periods of time, even in patients with cognitive impairment.⁷¹

Sleep Hygiene Education

Education regarding sleep hygiene consists of several interventions that promote healthy stable sleep and a nondisruptive sleep environment. These include avoiding daytime naps, maintaining a regular sleep schedule, limiting substances such as caffeinated beverages, nicotine, and alcohol that adversely affect sleep, and exercising at least 6 hours before bedtime.^72,73

Cognitive Behavioral Therapy for Insomnia

When sleep hygiene is not effective, Cognitive Behavioral Therapy for Insomnia (CBT-I), effective in older adults, should be attempted.^73–75 The American College of Physicians recommends CBT-I as first-line management for insomnia in adults.⁷⁶ It consists of 6 to 10 sessions with a trained therapist that focus on cognitive beliefs and counterproductive behaviors that interfere with sleep.

Sleep Restriction Therapy

This therapy involves restricting time in bed to the number of hours of actual sleep, until sleep efficiency improves. If after 10 days sleep efficiency remains lower than 85%, sleep time in bed should be restricted by 15 to 30 minutes until sleep efficiency improves. Time in bed is gradually advanced by 15 to 30 minutes when the time spent asleep exceeds 85% of total time in bed.⁷⁷

Stimulus Control Therapy

This therapy attempts to reassociate use of the bed and the desired bedtime to sleep only. This includes going to bed only when one feels tired, not using bed for reading, working, or lounging, leaving the bed if unable to sleep in 15 to 20 minutes, and maintaining a constant wake-up time each morning.⁷⁸

Relaxation Techniques

These include progressive muscle tensing and relaxing, guided imagery, paced diaphragmatic breathing, or meditation.²⁵

Brief Behavioral Therapy for Insomnia

Due to financial constraints and lack of psychological resources needed for CBT-I, a shorter form of therapy known as brief behavioral therapy for insomnia is also available and involves core techniques from CBT-I, directed at improving circadian regulation of sleep in more than two sessions. It has been found to be effective in the geriatric population, with benefits persisting for 6 months and beyond.⁷⁹ Internet-based behavioral therapies have also been found to be effective in older populations.⁸⁰ Multicomponent cognitive behavioral therapy that involves sleep hygiene measures, relaxation techniques, sleep restriction, and stimulus control is also as effective in older adults as a stand-alone treatment.^81,82

Pharmacological

There are several pharmacological options available for use in older patients with insomnia. Pharmacological treatments are primarily classified as benzodiazepine sedatives, nonbenzodiazepine sedatives, melatonin receptor agonists, antidepressants, and orexin receptor antagonists. Recently published clinical practice guidelines of the American Academy of Sleep Medicine for the pharmacological treatment of chronic insomnia represent an evidence-based review of each class of drug commonly used in the treatment of insomnia.⁸³

Benzodiazepines and Nonbenzodiazepine Sedatives

Both benzodiazepines and nonbenzodiazepine receptor agonists have a common mechanism of action. They work by binding to a specific receptor site on gamma-aminobutyric acid type A receptors, with the difference being nonbenzodiazepines are more selective for the alpha-1 subclass of receptors, which while causing sedation has minimal anxiolytic, amnesic, and anticonvulsant effects compared to that of benzodiazepines.⁸⁴ Both classes of drugs effectively treat insomnia-related parameters such as sleep onset latency, number of nighttime awakenings, total sleep time, and sleep quality in the short term, but not with chronic use.^85–87

Prolonged use of these drugs can lead to tolerance, dependence, rebound insomnia, residual daytime sedation, motor incoordination, cognitive impairment, and increased risk of falls in institutionalized older individuals.⁸⁸ These drugs can have additive effects if taken together. Because of these adverse effects, and the equivalent or superior response seen with CBT-I for longer duration therapy, use of these drugs should be avoided in older individuals. The recent 2015 Beers criteria strongly advise avoiding these drugs in the elderly.⁸⁹

Pharmacokinetic properties of these drugs dictate the differences between the drug effects on sleep parameters. Zolpidem has a shorter half-life (2 to 3 hours) and so may have less potential for residual daytime adverse events than zopiclone, which has a longer half-life (5 to 6 hours). However, the shorter half-life of zolpidem renders it less useful in treating sleep maintenance insomnia. These drugs have a faster onset of action and therefore can be used in treating sleep onset insomnia (reduce sleep onset latency).⁸⁴

Although the benefits outweigh the harms, there have been reports of impairment in daytime concentration tasks, such as driving while on zopiclone.^90,91 In women, in whom zolpidem clearance occurs more slowly than in men, morning blood levels following the recommended previous bedtime dose could be considerably higher, affecting psychomotor performance.⁹² In 2013, this led the United States Food and Drug Administration (FDA) to require the manufacturers of zolpidem to lower the recommended dose, particularly for women, from 10 mg to 5 mg for immediate-release preparations, and 12.5 mg to 6.5 mg for extended-release forms. It also required manufacturers to lower the recommended doses for men.

Antidepressants

Various antidepressants, including phenylpiperazine compounds (trazodone), tricyclic antidepressants (doxepin), and serotonergic antidepressant (mirtazapine), have sedating properties and are often used for the treatment of insomnia. Trazodone: It is widely prescribed for insomnia in doses of 25 to 100 mg. A study on trazodone comparing its effect with zolpidem in 21 to 65 year olds showed it has similar efficacy for sleep latency and sleep efficiency, with these effects dissipating after the first week.⁹³ Adverse events such as dizziness, cardiac arrhythmias, orthostatic hypotension, and potential priapism can be significant in the elderly population.⁹⁴ Clinical practice guidelines from the American Academy of Sleep Medicine suggest that clinicians not use trazodone for sleep onset or maintenance insomnia because its harms outweigh benefits.⁸³

Doxepin: Of all the antidepressants, only doxepin is FDA approved for insomnia at doses of 3 to 6 mg. It is selective for histamine 1 receptors. Studies of men and women age 65 years and older with doses of 1 mg and 3 mg have shown that doxepin 1 mg and 3 mg significantly improved measures of sleep onset (patient reported), sleep duration, sleep quality, and global treatment outcomes over the 12-week study period.⁹⁵ Higher doses of doxepin 3 mg and 6 mg to adults (18 to 64 years) with chronic primary insomnia has also been reported to lead to significant and sustained improvements in sleep maintenance and early morning awakenings.⁹⁶

Mirtazapine: This antidepressant with strong 5-HT2 antagonism may also improve insomnia. In a study of adults age 18 to 75 years old with mean age of 40.9 years, the mirtazapine group had significant improvement in sleep latency, sleep efficiency, and awakenings after sleep onset after only 2 weeks of treatment.⁹⁷ It may be preferred over other drugs as it produces sedative effects solely through histamine receptor antagonism.⁹⁷ Because of conflicting evidence and habituation to its sedative effects, it should not be used to treat insomnia in the absence of depression.

Melatonin Receptor Agonists

Ramelteon: It is also FDA approved for treatment of insomnia. In a study of older adults (age 65 years or older), treatment with ramelteon significantly reduced patient reports of sleep latency over 5 weeks of treatment with no significant rebound insomnia or withdrawal effects.⁹⁸ It is not associated with dependence, memory disturbances, and nocturnal gait instability in older individuals.^99,100

Herbal Supplements

Valerian: As a dietary supplement it lacks FDA approval and monitoring. Its mechanism of action is believed to occur through interaction with the neurotransmitter gamma amino-butyric acid and its receptors. There are limited studies of valerian in elderly individuals and data are lacking in terms of its efficiency in treating insomnia.

Melatonin: Melatonin at a dose of 2 mg has been approved in Europe for the short-term treatment of insomnia in patients age 55 years and older based on decline in melatonin production seen with age.¹⁰¹ Treatment has been shown to be effective for primary insomnia in some studies; however, formal recommendations for the use of melatonin in the treatment of insomnia requires further research.^83,101,102

Orexin Receptor Antagonists

Suvorexant: It is the first FDA-approved dual orexin receptor antagonist and may be prescribed up to a 20-mg dose. It targets wakefulness-promoting neuropeptides that regulate the sleep-wake cycle, demonstrating its efficacy in decreasing sleep latency and in increasing total sleep time. Suvorexant has been studied in both elderly (age 65 years or older) and non-elderly (age 18 to 64 years) patients, identifying no significant efficacy or safety differences between these two groups.¹⁰³ Although it is well tolerated by older adults, long-term data are still lacking.^103–105

CONCLUSIONS

Insomnia is very prevalent in older adults. Using the history and physical examination along with insomnia scales, clinicians can evaluate and treat insomnia in our rapidly aging population. Behavioral and cognitive behavioral therapies offer very effective longer duration treatment and are recommended as first-line treatment options for insomnia compared to hypnotic medications in older adults.

DISCLOSURE STATEMENT

All authors have seen and approved the manuscript. The authors report no conflicts of interest.

ABBREVIATIONS

CBT-I

cognitive behavioral therapy for insomnia

DSM

Diagnostic and Statistical Manual for Mental Disorders

FDA

United States Food and Drug Administration

ICD

International Statistical Classification of Diseases and Related Health Problems

ICSD

International Classification of Sleep Disorders

NREM

non-rapid eye movement

REM

rapid eye movement