November/December 2014

Insomnia Management
By Mark D. Coggins, PharmD, CGP, FASCP
Today's Geriatric Medicine
Vol. 7 No. 6 P. 6

Download tables here.

Insomnia, the repeated difficulty with sleep initiation, maintenance, duration, and/or quality of sleep that results in daytime impairment, affects nearly one-half of older adults over the age of 60. Sleep architecture changes occurring with increasing age often result in an increased time to fall asleep, an overall decline in REM sleep, and an increase in sleep fragmentation. Changes in circadian rhythms also affect sleep in older adults.

Insomnia may be acute or transient (lasting less than one week), short-term (lasting one to four weeks), or chronic (lasting longer than one month).1

Primary insomnia is sleeplessness that cannot be attributed to existing medical, psychiatric, or environmental causes. Secondary insomnia is often chronic and occurs as a result of other problems including the following:2,3

• chronic medical conditions such as congestive heart failure, arthritis, or pulmonary disorders;

• psychiatric conditions, including depression, anxiety, or delirium;

• medications (see table);

• use of stimulants such as caffeine;

• Alzheimer's disease (AD); and

• movement disorders such as restless leg syndrome.

Psychosocial factors such as isolation, loneliness, bereavement, decreased activity, or financial constraints and other late-life stressors, including declining health and relocation to a different living situation, can also contribute to insomnia.4

Environmental factors (see sidebar below) should be ruled out as causes of insomnia and are common in long term care facilities.4

Insomnia affects quality of life because of the effects of daytime dysfunction including fatigue, moodiness, irritability or anger, daytime sleepiness, anxiety about sleep, lack of concentration and motivation, poor memory, headaches, and increased accidents.3

Treating Insomnia
Determining the underlying cause of insomnia is essential before starting sleep medications. Recognizing and treating comorbid conditions such as major depression, medical disorders, or chronic pain are essential as are identifying and modifying inappropriate intake of caffeine, alcohol, and self-medication. Adjusting the timing or changing current medications known to contribute to insomnia may also provide benefits.1

Treating insomnia can significantly improve overall patient health. The American Academy of Sleep Medicine recommends pharmacological and nonpharmacological interventions, such as cognitive behavioral therapy (CBT), for the treatment of insomnia; however, behavioral therapies should be considered first-line treatments in primary insomnia, especially in older adults who are vulnerable to adverse effects of hypnotic medications. Head-to-head comparison has shown that the long-term benefits of nonpharmacologic interventions are superior to those of medications.
CBT has benefits that extend well beyond the end of treatment with certain interventions resulting in positive outcomes with continuation and improvement of sleep patterns for at least two years.1 Studies report that the majority of patients who are treated with nondrug methods experience improved sleep. Furthermore, most of those who have been taking drugs are able to stop or reduce their use.

CBT involves combinations of the following therapies1,2:

• cognitive therapy: changing attitudes/beliefs that hinder sleep;

• relaxation training and biofeedback: encouraging relaxation;

• sleep restriction: severely limiting and then gradually increasing time in bed;

• sleep hygiene training and stimulus control: correcting bad sleep habits; and

• basic goals of behavioral methods including reducing the time it takes to go to sleep to below 30 minutes and reducing wake-up periods during the night.

Although nonpharmacological interventions have demonstrated efficacy in managing sleep disturbances, a 2012 report on quality in Texas nursing homes indicated that only 12% of residents with sleep problems had nonpharmacological interventions attempted prior to initiating the use of sedative/hypnotic medications. Additionally, 12% of residents continued to have sleep problems despite the use of medication.3

Benefits of CBT in Reducing Inflammation
A recent study published in the journal Sleep found that patients treated for insomnia experienced reductions in inflammation comparable to the benefits reported with vigorous physical activity or weight loss.5 C-reactive protein (CRP), a known marker of inflammation, increases when insomnia is left untreated. With treatment of insomnia, CRP remained low even 16 months following treatment.

The study found that CBT performed better than tai chi chih and sleep seminar education in reducing insomnia, and produced greater and more sustained improvements in sleep quality, the ability to maintain continuous sleep throughout the night, and study participants' reports of fatigue and depressive symptoms.

Importance of Activities, Light, and Exercise
Older adults with more medical impairments spend more time in bed, often with limited time spent outdoors where they would be exposed to natural light. In the community, elderly patients with mild dementia have been reported to receive fewer than 30 minutes of bright light exposure per day, while long term care residents' exposure can be as low as 10 minutes per day. Diminished light exposure, lack of physical activity, and limited regular social interaction influence circadian rhythm regulation, resulting in early morning awakenings and fragmented sleep. Reduced light exposure in dementia patients has been shown to correlate with more severe dementia.6

Individualized Behavioral Interventions
Behavioral interventions to improve sleep should be tailored to meet the needs of each patient, and are especially important in long term care residents. Patients' specific needs should be evaluated with therapies chosen to target behaviors most likely to impact individual residents' sleep problems.

Cognitive impairment places limitations on CBT in patients with dementia; however, behavioral and environmental interventions, including reducing in-bed time during the day, increasing social and physical activity, and altering a patient's environment can provide significant benefits. This has been demonstrated in the Nighttime Insomnia Treatment and Education for Alzheimer's Disease program, which involved an eight-week combined intervention that included sleep hygiene education, daily walking (30 minutes), and increased light exposure (light box used for one hour per day). These interventions reduced the time spent awake during the night by 32% compared with controls, with effects maintained at a six-month follow-up.6

Insomnia Medications
Benzodiazepines (eg, diazepam, clonazepam) are widely used; however, these medications can be dangerous in the elderly who are at increased risk of next-day sedation, dizziness, weakness, confusion, physical dependence, agitation, and falls. Additionally, studies indicate that users of benzodiazepines tend to report poorer sleep quality than nonusers.

A recent study published in BMJ has linked the use of benzodiazepines to an increased risk of AD. The case-control study of nearly 9,000 older patients found that the risk for AD increased by 43% to 51% in patients who had used benzodiazepines in the previous five years. The association between AD and benzodiazepines was even higher in those patients receiving a benzodiazepine for six months or longer and in those using long-acting agents.7 Although the study does not prove a definitive link between benzodiazepine use and AD, the findings are significant and provide another reason for prescribers to use caution before using these medications in older adults.

Nonbenzodiazepines (eg, zolpidem [Ambien], zaleplon, eszopiclone) may be safer alternatives to benzodiazepines for insomnia due to less rebound insomnia or withdrawal symptoms following discontinuation; however, adverse effects such as delirium, falls, and fractures are similar to benzodiazepines. A case-crossover study of nursing home residents found patients receiving nonbenzodiazepines had an increased risk of hip fracture. The risk was even higher for new users and in residents with cognitive impairment.8 Nonbenzodiazepines should be used with caution in older adults and for no longer than 90 days. Studies have shown these agents to provide minimal improvement in sleep latency and duration.

Sedating antihistamines such as diphenhydramine (Tylenol PM) and doxylamine (Unisom) are commonly used active ingredients in over-the-counter sleep preparations. These medications are discouraged for insomnia in older adults because of their strong anticholinergic properties and the increased risk of confusion, dry mouth, and constipation.

Sedating antidepressants, such as trazodone, mirtazapine, and doxepin, are often prescribed for insomnia. Doxepin used at low doses is a selective histamine antagonist. Studies have shown doxepin at low doses improves sleep in older adults with a safety profile similar to placebo. High doses, greater than 6 mg should be avoided because of significant anticholinergic side effects.

Mirtazapine (Remeron) exhibits noradrenergic, serotonergic, and histaminic activity. It is believed the short-term effects on sleep benefit are related to antagonism of both serotonergic (5-HT2) and histamine (H1) receptors. Long-term sleep benefit appears to be related to antagonism of 5-HT2 receptors because tolerance to mirtazapine's histaminic effects develops in seven to 10 days. Daily doses of ≤30 mg tend to produce better sleep outcomes. In cases of depression associated with severe insomnia and anxiety, mirtazapine has been shown to be superior to other selective serotonin reuptake inhibitors. The potential for increased weight gain may prevent mirtazapine from becoming an agent of choice in some patients.9

Trazodone is an antagonist at the 5-HT2 receptor and minimally inhibits the reuptake of 5-HT. Trazodone is not associated with tolerance or withdrawal effects but it may prolong the QTc interval. Associated orthostatic hypotension can be minimized when trazodone is administered with food. Limited data exist in nondepressed patients and in older adults.

Melatonin and melatonin agonists may be useful to help promote sleep. Endogenous melatonin, which helps regulate circadian rhythm, undergoes a reduction with increasing age, and this reduction is thought to contribute to insomnia.

Administration one to two hours before bedtime can help mimic natural melatonin secretion and improve the circadian regulation of the normal sleep-wake cycle. Use of melatonin in older adults with primary insomnia has shown improvements relative to placebo in sleep quality and latency, morning alertness, and health-related quality of life.

Ramelteon is a melatonin receptor agonist with high selectivity for human MT1 and MT2 receptors thought to promote sleep and maintain circadian rhythm and a normal sleep-wake cycle. Ramelteon does not cause rebound insomnia or withdrawal symptoms at discontinuation. It is approved for prolonged use and is indicated for insomnia characterized by difficulty with sleep onset.

Suvorexant (Belsomra), an orexin receptor antagonist and the first drug of its kind, was approved in August for the treatment of insomnia after the manufacturer lowered the dosages to satisfy FDA safety concerns. Suvorexant is available in four strengths (5 mg, 10 mg, 15 mg, and 20 mg) with a total dosage not to exceed 20 mg in a single day. It is classified as a Schedule IV controlled substance.

Suvorexant alters the signaling of orexin neurotransmitters responsible for regulating the sleep-wake cycle. During FDA trials, participants receiving suvorexant fell asleep more quickly and spent less time awake for the rest of the night compared with participants given a placebo. In next-day driving tests, both male and female participants who took the 20-mg dose were impaired drivers. Physicians are advised to caution patients with dosage at high levels against next-day driving or other activities requiring full alertness.10 Suvorexant should be used with extreme caution in older patients, as data on its effects on this population are limited.

— Mark D. Coggins, PharmD, CGP, FASCP, is senior director of pharmacy services for skilled nursing centers operated by Diversicare in eight states, and is a director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

Environmental Factors Leading to Insomnia in Long Term Care Facilities4

• High noise level

• Patient care routines inconsistent with previous home daily routines

• Inadequate time outside with exposure to natural light and fresh air

• Temperature (too hot or too cold)

• Patient fear or loss of a feeling of security (unfamiliar environment)

• Lack of exercise or mobility

References
1. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.

2. Insomnia fact sheet. American Academy of Sleep Medicine website. http://www.aasmnet.org/resources/factsheets/insomnia.pdf. Accessed September 20, 2014.

3. Nursing facility quality review 2012 report. Texas Department of Aging and Disability Services website. Available at http://www.dads.state.tx.us/news_info/publications/legislative/nfqr2012/nfqr201
2.pdf. Updated January 2013. Accessed September 20, 2014.

4. Bergeron CA, Creceilius CA, Murphy R, et al. Improving sleep management in the elderly. Ann Long-Term Care. 2007;15(12).

5. Irwin MR, Olmstead R, Carrillo C, et al. Cognitive behavioral therapy vs. tai chi for late life insomnia and inflammatory risk: a randomized controlled comparative efficacy trial. Sleep. 2014;37(9):1543-1552.

6. Teodorescu M. Sleep disruptions and insomnia in older adults. Consultant. 2014;54(3):166-173.

7. Billioti de Gage S, Moride Y, Ducruet T, et al. Benzodiazepine use and risk of Alzheimer's disease: case-control study. BMJ. 2014;349:g5205.

8. Berry SD, Lee Y, Cai S, Dore DD. Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents. JAMA Intern Med. 2013;173(9):754-761.

9. Dolder CR, Nelson MH, Iler CA. The effects of mirtazapine on sleep in patients with major depressive disorder. Ann Clin Psych. 2012;24(3):215-224.

10. FDA approves new type of sleep drug, Belsomra. FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm409950.htm. Updated August 13, 2014. Accessed October 7, 2014.