Psychiatric Annals

CME Article 

Treatment of Sleep Disturbances in Nursing Home Patients: Practical Management Strategies

Kristina M. Reinstatler, PharmD, BCPP, MBA; Brittany Woolf, PharmD, BCPS

Abstract

Sleep disorders are a significant issue in the nursing home population, with prevalence rates from 6% to 65%. They can lead to several deleterious effects, such as increasing malaise, falls, and cognitive decline. There are a variety of treatment options, with nonpharmacologic interventions being first line. If nonpharmacologic measures fail, pharmacotherapy can be considered. Melatonin agonists, select antidepressants, suvorexant, and magnesium supplements have data to support their use in the elderly patient with minimal side effects. Medications with safety profiles that indicate the risks may outweigh the benefits should be avoided. These include benzodiazepines, nonbenzodiazepine hypnotics, antihistamines, antipsychotics, and most tricyclic antidepressants. Additionally, the lowest effective dose of any medication is recommended to minimize adverse effects. [Psychiatr Ann. 2018;48(6):271–278.]

Abstract

Sleep disorders are a significant issue in the nursing home population, with prevalence rates from 6% to 65%. They can lead to several deleterious effects, such as increasing malaise, falls, and cognitive decline. There are a variety of treatment options, with nonpharmacologic interventions being first line. If nonpharmacologic measures fail, pharmacotherapy can be considered. Melatonin agonists, select antidepressants, suvorexant, and magnesium supplements have data to support their use in the elderly patient with minimal side effects. Medications with safety profiles that indicate the risks may outweigh the benefits should be avoided. These include benzodiazepines, nonbenzodiazepine hypnotics, antihistamines, antipsychotics, and most tricyclic antidepressants. Additionally, the lowest effective dose of any medication is recommended to minimize adverse effects. [Psychiatr Ann. 2018;48(6):271–278.]

As people age, they experience increasing difficulty with sleep for a variety of reasons, including decreased slow-wave sleep,1,2 more sleep fragmentation, earlier awakening, and changes in the circadian rhythm.2 Older adults are also more likely to have diseases that affect sleep patterns.2

Sleep disorders are common and more severe in nursing home residents than those living in the community.1 Reported prevalence rates for insomnia in nursing home patients are from 6% to 65%.3,4 Impaired sleep can have a number of deleterious effects on quality of life in the older adult population.1 Nursing home residents may become physically and mentally fatigued, anxious, and irritable, and as bedtime approaches worry and anxiety can worsen.5 Poor sleep may also negatively affect health by increasing the risk of accidents, malaise, chronic fatigue, falls, and cognitive decline. Sleep quality affects memory, concentration, and performance on psychomotor tests. Sleep disturbance is also associated with a higher rate of mortality in the elderly.5

Nonpharmacologic

Before initiating medications for insomnia, it is important to ensure that nonpharmacologic approaches have been explored and implemented. If the resident has an underlying issue causing insomnia, address those issues first. Ensure proper sleep-hygiene is being practiced. Increasing activity level, minimizing light and noise exposure, and maintaining a comfortable temperature are recommended.5 A meta-analysis comparing behavioral therapy to benzodiazepines or benzodiazepine receptor agonists showed similar outcomes, with behavioral therapy having improved sleep latency.6 The NITE-AD (Nighttime Insomnia Treatment and Education for Alzheimer's Disease) trial compared a sleep hygiene program to general education in 36 patients with dementia who resided at home. The treatment group had decreased nighttime awakenings, total awake time, and depression.7

Sedative Hypnotics

Benzodiazepines

Benzodiazepines improve insomnia by shortening sleep onset latency and decreasing nocturnal awakenings.8 Several benzodiazepines are US Food and Drug Administration (FDA) approved for short-term treatment of insomnia, including triazolam and temazepam.8 Benzodiazepines have been studied in older adults and nursing home residents (Table 1).

Sedative Hypnotics Evidence for Treatment of Insomnia

Table 1:

Sedative Hypnotics Evidence for Treatment of Insomnia

Despite many safety concerns, benzodiazepines are frequently used in older adults. They are associated with confusion, memory impairment, daytime drowsiness, and impaired balance, which could lead to falls.13,14 Long-acting agents, such as clonazepam and diazepam, may be appropriate for rapid eye movement sleep behavior disorders, but according to the Beers Criteria, short- and intermediate-acting benzodiazepines should be avoided in the elderly.14

Nonbenzodiazepine Hypnotics

Zolpidem, Zaleplon, and Eszopiclone

In meta-analysis data submitted to the FDA, it was found that nonbenzodiazepine hypnotics, or “Z drugs,” reduce polysomnographic and subjective sleep latency. However, these effect sizes are considered to lack clinical significance. “Z drugs” are more likely to be effective in reducing sleep latency in younger or women patients, or if zolpidem is used.15 The efficacy of nonbenzodiazepine hypnotics has been studied in the elderly (Table 1).

Nonbenzodiazepine hypnotics are associated with adverse effects, such as cognitive or psychomotor effects, daytime fatigue, tolerance, addiction, and excess mortality. There seems to be no significant difference from benzodiazepines.15 The Beers Criteria recommend avoiding “Z drugs” as they have adverse events similar to those of benzodiazepines in older adults, are associated with increased emergency department visits and hospitalizations, and have demonstrated minimal improvement in sleep latency and duration.14 Additionally, Glass10 found that for older adults treated with sedative hypnotics, the number needed to treat for improved sleep quality was 13 and the number needed to harm for any adverse event was 6.

Melatonin Agonists

Melatonin is thought to decline as a person ages and this leads to sleep disturbances.19 There are conflicting data regarding the usefulness of melatonin supplementation, especially in older adults.

Lemoine et al.20 evaluated the prolonged melatonin release of a 2-mg dose versus placebo in patients older than age 55 years with primary insomnia. The melatonin group had a statistically significant improvement in sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ).20 A similar study comparing melatonin prolonged release of a 2-mg dose versus placebo showed improved sleep quality as assessed by a polysomnogram in addition to the LSEQ questionnaire.21

Adults with Alzheimer's disease have been shown to have low levels of melatonin,19 so several studies have evaluated the benefits of melatonin in this population. A study by Gehrman et al.22 showed no difference in the treatment effect of melatonin at a dose of 10 mg (8.5-mg dose immediate release plus 1.5-mg dose time release) in 41 patients with Alzheimer's disease who resided in a nursing home. However, a large study from the Netherlands compared placebo, circadian stimuli light therapy, melatonin immediate release of a 2.5-mg dose, and melatonin plus light therapy in 189 patients who resided in assisted living facilities.23 Of the 189 patients, 87% had some degree of dementia. At the 3.5-year follow-up visit, the investigators found melatonin, alone or with light therapy, improved sleep latency and duration.23

Ramelteon is more selective and has a longer half-life than melatonin.19 Roth et al.24 studied ramelteon in 829 adults older than age 65 years with primary insomnia. Patients were randomized to receive ramelteon at a dose of 4 mg, 8 mg, or placebo. They found that those who received ramelteon had a statistically significant reduction in sleep latency.24 Zammit et al.25 evaluated the effects ramelteon at a dose of 8 mg, zolpidem at a dose of 10 mg, and placebo on middle-of-the night balance, mobility, and memory in adults older than age 65 years. Zolpidem was associated with impairment and ramelteon was not when compared to placebo.25

Antidepressants

Trazodone

Trazodone is often prescribed for insomnia at doses subtherapeutic for depression, usually a dose of 100 mg or less.26 There are few studies examining trazodone for primary insomnia; more data are available for secondary insomnia due to depression.8,26 See Table 2 for trials conducted in an older adult population.

Antidepressants Evidence for Treatment of InsomniaAntidepressants Evidence for Treatment of Insomnia

Table 2:

Antidepressants Evidence for Treatment of Insomnia

Trazodone's notable side effects include dizziness, sedation, headache, nausea/vomiting, edema, blurred vision, constipation, dry mouth, incoordination, and tremor.29 Cardiac effects include hypotension, syncope, sinus bradycardia, ventricular arrhythmias, and cardiac conduction disturbances, including torsades de pointes.26,29

Mirtazapine

Mirtazapine has been found to promote sleep, improve sleep continuity, and increase low-delta activity.30 However, there are little data to support the use of mirtazapine for insomnia without a coexisting mood disorder.31 Only two trials32,33 specifically examine sleep in elderly patients with depression. For older adults with dementia, there is also a lack of data.

Side effects associated with mirtazapine include dry mouth, constipation, increased appetite, weight gain, sedation, dizziness, confusion, and abnormal dreams. Also reported are flu-like symptoms, changes in urinary function, and hypotension.29

Doxepin

At low doses, doxepin has a high affinity for the histamine H1 receptor, which promotes and maintains sleep. In 2010, the FDA approved a low-dose formulation of doxepin specifically for the treatment of insomnia.36 Three studies have been conducted using doxepin in older adults for primary insomnia and are summarized in Table 2.

At higher doses, doxepin is associated with blurred vision, constipation, urinary retention, increased appetite, dry mouth, weight gain, dizziness, sedation, restlessness, and anxiety.29 Side effects can be minimized by keeping doses low,36 with the most common being somnolence and sedation when the dose is <6 mg/day.29 The Beers Criteria include doxepin as a medication to avoid at a dose >6 mg/day.14

Amitriptyline and Other Tricyclic Antidepressants

There is little evidence for the use of other tricyclic antidepressants (TCAs) in sleep. The side-effect profile of TCAs limits their use, especially in the elderly. Dry mouth, difficulty in micturition, constipation, fine tremor, drowsiness, orthostatic hypotension, and weight gain are all potential effects. In the elderly, there is also a risk of impaired cognition and potential for delirium.36 The Beers Criteria issue a strong warning to avoid use of TCAs in the elderly.14

Orexin Receptor Antagonist

Suvorexant is an orexin receptor antagonist that is thought to improve sleep through dampening the orexin-mediated wakefulness system of the brain.40 A recent pooled analysis40 of data in the elderly from two phase III trials included 839 patients older than age 65 years. Suvorexant at doses of 30 mg and 15 mg were both found to statistically improve subjective and polysomnographic measures of sleep. The most common adverse event was somnolence, with excessive daytime sleepiness being more common in patients on suvorexant versus placebo. The percentage of falls was similar for each suvorexant group compared to placebo. There was no evidence of withdrawal symptoms and minor evidence of rebound insomnia in patients abruptly discontinued.41

Antihistamines

There are few studies evaluating the effectiveness of antihistamines in nursing home residents. This is due to the avoidance of antihistamines in the elderly due to cognitive impairment and anticholinergic effects.5 Glass42 compared diphenhydramine at a dose of 50 mg, temazepam at a dose of 15 mg, and placebo in 20 elderly patients with insomnia and found diphenhydramine improved number of awakenings compared to placebo. Adverse effects were similar between groups.42

Antipsychotics

Antipsychotics, particularly those with sedating properties, are used off-label for insomnia.43 Guidelines44 and reviews43,45 have found a lack of evidence to support this off-label use. They suggest avoidance of off-label administration of these drugs, given the weak level of evidence supporting their efficacy for insomnia when used alone and the potential for significant side effects.44

Quetiapine is the most frequently prescribed antipsychotic for sleep and sedation.46,47 There have been a variety of studies examining the efficacy of quetiapine in primary insomnia and insomnia related to other psychiatric conditions. Most of these studies are small and in patients with a mean age of 40 to 55 years.45 Active comparator studies are not available for quetiapine in insomnia.48 No published trials were found using antipsychotics for sleep in a nursing home population; however, Yamashita49 found elderly inpatients with schizophrenia had improved subjective sleep quality after 8 weeks of treatment with quetiapine, olanzapine, or risperidone.

There is concern for using antipsychotics in an elderly population. Antipsychotics are associated with an increased risk of adverse effects, including cerebrovascular events, extrapyramidal symptoms, metabolic disease, and sudden cardiac death.48 All antipsychotics carry a black box warning from the FDA regarding increased mortality in patients with dementia.50 Additionally, a recent warning linked the use of atypical antipsychotics and sleep apnea.51

Based on the American Psychiatric Association's Choosing Wisely recommendations, clinicians should limit the use of antipsychotic medications to cases where nonpharmacologic measures have failed and the patients' symptoms may create a threat to themselves or others.52 The Beers Criteria agrees with this stance and recommends avoiding antipsychotics in the elderly unless treating schizophrenia, bipolar disorder, or for nausea in chemotherapy.14

Supplements

There are very few studies evaluating supplements for sleep in the elderly. The existing data for the elderly evaluates magnesium. Magnesium supplementation has been found to increase slow wave sleep, delta power, and sigma power.53

Magnesium deficiency is common in the elderly population due to decreased intake. In a study comparing a 500-mg dose of elemental magnesium to placebo in 46 older adults with insomnia, the supplementation group had increases in sleep time and sleep efficiency but not in total sleep time. The insomnia severity index worsened in both groups.54 Nielsen et al.55 studied a dose of 320 mg of magnesium in 100 patients with poor sleep quality. Overall Pittsburgh Sleep Quality Index (PSQI) scores increased in both the treatment and placebo groups.55

There are few studies specifically looking at supplements in the nursing home population. In evaluating a supplement containing melatonin, magnesium, and zinc versus placebo in 43 long-term care patients, the supplement group was found to have better PSQI scores.56 Wouters-Wesseling57 studied a magnesium-containing supplement in residential adults and found the supplement to be statistically significant compared to placebo for improving sleep.

Conclusion

For treatment of sleep disturbances in nursing home residents, nonpharmacologic treatment should be first line. If pharmacologic treatment is necessary, melatonin agonists, especially ramelteon, can be considered, or low-dose antidepressants such as trazodone (50–100 mg) or doxepin (≤6 mg) are options. If a patient has comorbid depression, mirtazapine is a good choice. Suvorexant and magnesium supplementation have shown promising results but more data are needed.

Medications that should be minimized due to their unfavorable safety profile include sedative hypnotics and antipsychotics. Antihistamines and tricyclic antidepressants, with the exception of low-dose doxepin, have safety concerns and a lack of evidence, and should therefore be avoided in nursing home residents.

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Sedative Hypnotics Evidence for Treatment of Insomnia

Source Intervention Population Outcomes
BZDs
Holbrook et al.9 BZD users vs placebo 2,672 patients BZDs significantly increased total sleep duration

Glass10 BZD users vs placebo 2,417 patients (mean age 60 years) BZDs increased sleep quality (P < .5) and total sleep time (P < .001), decreased number of awakenings (P < .001); small effect size; adverse effects more common with BZD

Bourgeois et al.11 BZD users vs nonusers 300 nursing home residents BZD use associated with poor sleep (r = 0.173, P = .003)

Chen et al.12 BZD users vs nonusers 383 nursing home residents Long-acting BZD users had higher night time sleep quality (AOR = 4, 95% CI 1.06–15.15); short-acting BZDs PRN use was associated with lower night time sleep quality and longer daytime napping

Non-BZD hypnotics (“Z drugs”)
Walsh et al.16 Zolpidem ER (6.25 mg) vs placebo 205 patients with primary insomnia (mean age 65–87 years) Zolpidem group showed significantly improved polysomnogram measures and patient-reported measures; no statistical difference was found in morning residual effects or treatment emergent adverse effects for the two groups

Ancoli-Israel et al.17 Zaleplon (5 mg and 10 mg) vs placebo; zolpidem (5 mg) active comparator 549 patients with primary insomnia (mean age ≥ 65 years) Week 1: zaleplon (10 mg) and zolpidem (5 mg) group significantly improved sleep latency and total sleep time Week 2: zaleplon (5 mg and 10 mg) and zolpidem (5 mg) group significantly improved sleep latency and total sleep time; zolpidem group showed a significantly greater incidence of rebound insomnia and central nervous system events compared to placebo, whereas the zaleplon group showed no difference

Ancoli-Israel et al.18 Eszopiclone (2 mg) vs placebo 388 patients with primary insomnia (mean age 65–85 years) Eszopiclone group had better total sleep time (P < .0001); eszopiclone significantly improved the subjective outcomes of total sleep time, sleep latency, waking after sleep onset, daytime alertness, ability to function, ability to concentrate, and sense of physical well-being over placebo

Antidepressants Evidence for Treatment of Insomnia

Source Intervention Population Outcomes
Trazodone
Camargos et al.27 Trazodone 178 patients with dementia Sleep improvement in 65.7% treated with trazodone (50–100 mg)

Camargos et al.28 Trazodone (50 mg vs placebo) 30 outpatients with Alzheimer's disease Trazodone group spent more minutes asleep (P = .045) and had greater percent sleep (P = .013); trazodone did not induce significant daytime sleepiness or impair cognition

Mirtazapine
Savarese et al.31 Mirtazapine vs trazodone 79 patients with insomnia ± depression Trazodone group showed effective in 87.87%; mirtazapine effective in 86.95%; for patients age ≥65 years, 48.28% responded to trazodone and 45% responded to mirtazapine; responders were found to be on lower doses

Rothschild-Fuentes et al.32 Mirtazapine (30 mg) 10 outpatients with major depressive disorder (mean age ≥60 years) Significant improvement was found in depressive symptoms and subjective quality of sleep; no significant changes were observed in actigraphic recordings

Schatzberg et al.33 Mirtazapine vs paroxetine 246 outpatients (mean age ≥65 years) Mirtazapine group improved depressive symptoms (P < .05) and sleep disturbance (P < .05) vs paroxetine; adverse effects associated with mirtazapine were weight gain, dry mouth, somnolence, fatigue, dizziness, and nausea

Raji and Brady34 Mirtazapine 3 outpatients with dementia and depression Lessened insomnia

Scoralick et al.35 Mirtazapine (15 mg) vs placebo 24 outpatients with Alzheimer's disease (mean aeg ≥60 years) No statistically significant improvement in actigraphic measures; no effect on cognitive functional status

Doxepin
Scharf et al.37 Doxepin (1 mg, 3 mg, and 6 mg) vs placebo 76 patients with primary insomnia (mean age ≥65 years) All three doses significantly improved wake time during sleep, wake time after sleep onset, total sleep time, and overall sleep efficiency; no residual psychomotor impairment or sleepiness for any dose vs placebo

Krystal et al.38 Doxepin (1 mg and 3 mg) vs placebo 240 outpatients with primary insomnia (mean age ≥65 years) Doxepin had significant improvement in wake after sleep onset and total sleep time, sleep efficiency percent, and subjective sleep measures; no significant differences for doxepin vs placebo for next-day psychomotor function, subjective alertness, or drowsiness

Lankford et al.39 Doxepin (6 mg) vs placebo 254 outpatients with primary insomnia (mean age ≥65 years) Doxepin had significant improvements in subjective total sleep time, subjective wake after sleep onset, sleep quality, and the insomnia severity index
Authors

Kristina M. Reinstatler, PharmD, BCPP, MBA, is a Clinical Pharmacy Specialist, Department of Psychiatry. Brittany Woolf, PharmD, BCPS, is a Clinical Pharmacy Specialist, Internal Medicine. Both authors are affiliated with the University of Cincinnati Medical Center.

Address correspondence to Kristina M. Reinstatler, PharmD, BCPP, MBA, University of Cincinnati Medical Center, Ridgeway Pavilion, 3200 Burnet Avenue, Cincinnati, OH 45229; email: krissy.reinstatler@uchealth.com.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00485713-20180514-02

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