Geriatric Sleep Disorder Medication

Before any medications are prescribed, the first priority should be to determine the underlying cause of the sleep disorder, rather than just treat insomnia symptomatically. Usually, treatment on a short-term basis together with sleep hygiene is appropriate for transient insomnia, such as insomnia secondary to bereavement or acute hospitalization. Insomnia in this population is treated with antidepressants, benzodiazepines, nonbenzodiazepines, a melatonin agonist, and herbals. Medications, if used, should be started with a low dose and monitored for side effects.^[19]

In March of 2007, the FDA requested that the manufacturers of 13 sedative-hypnotic medications (eg, temazepam, flurazepam, triazolam, estazolam, zolpidem, zaleplon, eszopiclone, quazepam, ramelteon, butabarbital, and secobarbital) change their labeling to include stronger language about the risks of severe allergic reactions and complex sleep-related behaviors (eg, driving, making telephone calls, eating, having sex while not fully awake).

Class Summary

According to the 1990 National Institutes of Health (NIH) consensus statement, hypnotics should be used on a limited short-term period and should only be used for older adults with transient insomnia because of increased hypnotic-related adverse effects. Avoid over-the-counter hypnotics (eg, diphenhydramine) because they have strong anticholinergic effects.

Barbiturates also are not indicated for insomnia, and psychiatric consultation may become necessary for patients receiving barbiturates for many years. The advantage of chloral hydrate is its rapid onset and rapid metabolism, although whether it is safe and well tolerated in the older population is unclear. Barbiturates are effective only for short-term use, losing much of their effectiveness after 2 weeks of administration. They are not used for insomnia in older patients.

Benzodiazepines remain the most commonly prescribed agents for sleep. The major advantages of the benzodiazepines (short- and intermediate-acting) are their relative safety in overdose, lower addiction risk, and weak interaction with other drugs. They should be used for a maximum of 2-3 weeks; if used longer, they should be used for only 2-3 nights per week. Because continued use results in increased tolerance and increased dose, care must be taken to avoid dependence. While the short- and intermediate-acting benzodiazepines are less likely to be associated with falls and hips fractures than the barbiturates and the longer-acting benzodiazepines, they are still a risk factor for falls in the older population.

Benzodiazepines are also more likely to produce the most pronounced rebound and withdrawal symptoms after discontinuation of the drug. Tapering the dosage can reduce rebound insomnia after discontinuation of these agents. Do not use long-acting agents (eg, flurazepam) in the older population because of the long half-life (2-8 days) and the tendency to accumulate over several days or weeks. These drugs are associated with daytime sedation, lethargy, ataxia, falls, and cognitive and psychomotor impairment.

Newer nonbenzodiazepine hypnotics such as zolpidem, zaleplon, and eszoplicone do not cause rebound insomnia or withdrawal symptoms at discontinuation. Eszoplicone is approved for prolonged use.

Triazolam (Halcion)

Triazolam depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. It is rapidly absorbed and eliminated and may cause rebound insomnia, anterograde amnesia, and confusion, especially in elderly individuals.

Zolpidem (Ambien, Edluar, ZolpiMist)

Zolpidem is structurally dissimilar to benzodiazepines but similar in activity, with the exception of having reduced effects on skeletal muscle and seizure threshold. It has the advantage of no rebound insomnia or anxiety at discontinuation. At recommended doses, it is as effective as triazolam. Adverse CNS effects (eg, nightmares, agitation, drowsiness) have been noted in 10% of patients. As with benzodiazepine hypnotics, zolpidem is approved only for short-term use (maximum, 3-4 weeks); if used longer, they should be used for only 2-3 nights per week.

Zaleplon (Sonata)

Zaleplon is a short-acting pyrazolopyrimidine hypnotic with full agonistic activity on central benzodiazepine receptors (B21 type). At small doses, it is an effective sleep inducer, with limited risk of disturbance in morning performance. Like zolpidem, zaleplon is particularly suitable for treatment of initial insomnia and does not cause rebound insomnia and withdrawal symptoms at discontinuation. It is approved only for short-term use (maximum, 3-4 weeks); if used longer, it should be limited to only 2-3 nights per week.

Eszopiclone (Lunesta)

Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is believed to be an interaction with the GABA-receptor at binding domains close to or allosterically coupled to benzodiazepine receptors. It is indicated for insomnia to decrease sleep latency and improve sleep maintenance. Eszopiclone has a short half-life, of 6 hours. Higher doses (ie, 2 mg for elderly adults and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly adults and 2 mg for nonelderly adults) are suitable for difficulty in falling asleep.

Lorazepam (Ativan)

Lorazepam is a sedative hypnotic with a short onset of effects and a relatively long half-life. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including limbic and reticular formation. It is helpful for sleep maintenance and should be taken 30 minutes before bedtime. It causes less withdrawal and rebound than short-acting benzodiazepines, but it may cause more daytime sedation.

Temazepam (Restoril)

Temazepam depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of GABA. It is an intermediate-acting agent that is helpful for sleep-maintenance insomnia. If patients also have difficulty falling asleep, temazepam should be taken 30 minutes before bedtime. It causes less withdrawal and rebound than short-acting benzodiazepines, but it may cause more daytime sedation.

Class Summary

Sedating antidepressants (eg, trazodone, nefazodone) in low doses can also be prescribed at bedtime for insomnia. They are indicated for use when the patient has a previous history of substance abuse. As with other antidepressants, little scientific evidence supports efficacy in the treatment of insomnia without associated depression; their use in patients with insomnia without depression is not FDA approved and should be considered off-label use.

Doxepin (Silenor)

Doxepin increases concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. These effects are associated with a decrease in symptoms of depression.

Mirtazapine (Remeron)

Mirtazapine exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, mirtazapine has been shown to be superior to other SSRIs.

Trazodone (Oleptro)

Trazodone is an antagonist at the 5-HT2 receptor and minimally inhibits the reuptake of 5-HT. It has negligible affinity for cholinergic and histaminergic receptors. Trazodone is not associated with tolerance or withdrawal effects. Associated orthostatic hypotension can be minimized by administration with food. Limited data exist regarding efficacy in patients who are not depressed, and the FDA has not approved trazodone as a hypnotic.

Nefazodone

Nefazodone is an antagonist at the 5-HT2 receptor and inhibits the reuptake of 5-HT. It has negligible affinity for cholinergic and histaminergic receptors.

Class Summary

Melatonin agonists may promote sleep.

Ramelteon (Rozerem)

Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintaining 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. It is indicated for insomnia characterized by difficulty with sleep onset.