“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.
Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.
Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.
Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.
Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.
He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.