July/August 2009

Let’s Sleep on It
By Jennifer M. Voisine, PharmD, BCPS, and Sean M. Jeffery, PharmD, CGP, FASCP
Aging Well
Vol. 2 No. 3 P. 30

Insomnia is the most common sleep disturbance older adults experience, with a prevalence ranging from 20% to 40%. Lack of sleep can cause daytime somnolence, cognitive decline, depression, and an increased risk of falls. By definition, insomnia can include difficulty falling asleep or maintaining sleep or not feeling rested upon waking. The clinical diagnosis of insomnia designates that at least one of these symptoms exists and causes impairment concerning work-related or social activities.

Numerous factors can contribute to sleep problems. Older adults experience decreased total sleep time, more frequent awakenings throughout the night, and decreased sleep efficiency. Sleep disturbances may also result from chronic medical conditions, medications, and primary sleep disorders such as sleep apnea, restless leg syndrome, and periodic limb movements. Psychosocial factors, such as grief or bereavement, can also play a role.

Nonpharmacologic Management
When evaluating a patient for insomnia, practitioners must obtain a comprehensive history, including chronic conditions, medication use, and sleep habits. Professionals should always employ cognitive behavioral therapy (CBT) as a first-line treatment. Studies show that altering sleep habits has proven more effective than medications. One trial demonstrated that CBT reduced elapsed time to sleep onset in older adults with chronic and primary insomnia by 55% vs. 46% for elders treated pharmacologically. Additionally, only those who received behavioral therapy continued to see a long-term benefit.

CBT consists of maintaining a regular sleep schedule and ensuring a comfortable sleep environment (i.e., dim lighting and noise elimination). Stimulus-control therapy encourages using the bedroom for sleep only; patients should not watch television or eat while in bed. Relaxation therapy may be effective for older adults for whom hyperarousal is suspected as a cause of insomnia. Relaxation techniques include imagery and meditation.

Pharmacologic Management
In 2003, the National Sleep Foundation’s Sleep in America Poll reported that 15% of the older adults surveyed used a sleep aid every night or almost every night.

Benzodiazepines
Five benzodiazepines have FDA indications for the treatment of insomnia: estazolam, flurazepam, quazepam, temazepam, and triazolam. Benzodiazepines improve sleep latency and sleep continuity. Triazolam effectively decreases sleep latency due to its short onset of action. Temazepam has been used for patients who have difficulty with sleep maintenance because it has a longer duration of action.

When considering benzodiazepines for use in older adults, it’s best to choose one with a rapid onset of action, no active metabolites, a relatively short duration of action, and minimal drug-drug interactions. The half-lives of benzodiazepines may be prolonged in older adults, which can lead to a “hangover” effect. Benzodiazepines are associated with tolerance, dependency, and rebound insomnia. They can also impair cognition, decrease daytime alertness, and increase risk of falls, and older adults are especially sensitive to these effects.

Nonbenzodiazepines
Nonbenzodiazepines were developed with the intention of overcoming the adverse events associated with benzodiazepines. These agents, in general, cause less rebound insomnia, less abuse potential, fewer dependency problems, and less risk of a hangover effect. There are three nonbenzodiazepines available in the United States: zolpidem, zaleplon, and eszopiclone.

Zolpidem is indicated for the short-term management of insomnia (less than 10 days). It has a rapid onset and a relatively short duration of action. Zolpidem controlled release consists of a two-layer tablet: two thirds of the total dose is released immediately, and one third is released after three hours. Zolpidem controlled release is indicated for a longer duration of use, up to three weeks. Adverse events include dizziness, drowsiness, nausea, and upset stomach.

Zaleplon has a faster onset and shorter duration of action than zolpidem. Because of its short duration of action, it may be taken after the patient has gone to bed and experienced difficulty falling asleep, as long as there are at least four hours of sleep remaining. There are no published studies that look at during-the-night use of zaleplon in older adults. Adverse events include dizziness, headache, nausea, and somnolence.

Eszopiclone has an onset and duration of action similar to zolpidem. Like zolpidem controlled release, eszopiclone is not restricted to short-term use. Adverse effects include somnolence, headache, and unpleasant taste.

Melatonin Receptor Agonists
Ramelteon targets melatonin receptors, which are thought to be involved in the sleep-wake cycle. Similar to zolpidem controlled release and eszopiclone, ramelteon is indicated for long-term use. Ramelteon should be avoided in patients with severe liver impairment, and adverse effects include somnolence and dizziness.

Antidepressants
Trazodone is one of the most commonly prescribed antidepressants for the treatment of insomnia. It increases sleep duration; however, these effects may not last beyond two weeks if used daily. Adverse effects include sedation, dizziness, and cognitive impairment. Data on other antidepressants (including mirtazapine and amitriptyline) are lacking.

Other Sleep Aids
Almost 20% of older adults have admitted to managing sleep problems with either over-the-counter sleep aids or alcohol. Many over-the-counter products contain diphenhydramine, a medication that can cause urinary retention, constipation, and confusion and increase the risk of falls. Furthermore, diphenhydramine does not improve sleep quality. Alcohol may reduce sleep latency but is associated with poor sleep quality and increased nighttime awakenings.

There are several nutraceutical products marketed for the treatment of insomnia. Melatonin is an endogenous hormone that regulates circadian rhythm. Although melatonin may be effective in circadian rhythm disorders (e.g., jet lag), there is little evidence for efficacy in the treatment of insomnia.

Valerian is a plant derivative that is touted for promoting sleep. However, several case reports describe the incidence of hepatotoxicity with its use. And L-tryptophan is an endogenous amino acid that has been used as a hypnotic despite limited evidence.

Maintaining Vigilance
Sleep disorders are fairly pervasive among older adults. When assessing a patient for insomnia and exploring possible treatments, it is important to consider factors associated with normal aging, chronic diseases or medication use, and psychosocial issues. Behavioral therapy should always be used first. All sedative-hypnotics have adverse effects that include somnolence, dizziness, and increased risk of falls. Therefore, they should be used with caution in older adults. If drug therapy is implemented, it is prudent to monitor closely for efficacy and the incidence of adverse effects.

Drugs should be used at the lowest effective dose, and intermittent dosing (two to four times weekly) is preferred. Additionally, it’s advisable to attempt dosage reductions, and the medication should be gradually tapered and discontinued whenever possible.

— Jennifer M. Voisine, PharmD, BCPS, is a geriatric pharmacy resident at the VA Connecticut Healthcare System in West Haven and an adjunct professor at the University of Connecticut School of Pharmacy.

— Sean M. Jeffery, PharmD, CGP, FASCP, is an associate clinical professor at the University of Connecticut School of Pharmacy and a clinical specialist in geriatrics at the VA Connecticut Healthcare System department of pharmacy.