PHOENIX – It’s a good idea to remind insomnia patients not to mix benzodiazepine receptor agonists – zaleplon, zolpidem, and eszopiclone – with antihistamines, antinausea drugs such as promethazine, or alcohol.
Mixing the so-called Z-drugs with those or other sedating agents can trigger sleepwalking, sleep driving, or sleep eating, among other problems, in approximately 1 in 1,000 people. Those affected might "get up in the morning and find the kitchen is a mess and all the food is pulled out of the refrigerator. They’ll have no memory of it," said Dr. James Parish, medical director of the center for sleep medicine at the Mayo Clinic in Scottsdale, Ariz.
When Dr. Parish prescribes a Z-drug, "I warn people about this effect and [that] if this happens, they should stop [the drug] immediately and not use it again," he said.
Otherwise, the Z-drugs have a good safety profile. Sublingual zolpidem (Intermezzo), the most recent entry in the class, has a 2.5-hour half-life and can be used for middle-of-the-night insomnia if patients have at least 4 hours left in bed. Zaleplon (Sonata) has a 1-hour half-life and can also be used in the middle of night, Dr. Parish said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.
The Z-drugs, along with short- to intermediate-acting benzodiazepines and ramelteon (Rozerem), are first-line options for insomnia, according to American Academy of Sleep Medicine guidelines (J. Clin. Sleep Med. 2008;4:487-504).
Benzodiazepines with longer half-lives and active metabolites should be avoided for insomnia, Dr. Parish said. These agents can cause daytime sleepiness and cognitive impairment, among other problems, especially in elderly people less able to metabolize them.
After months or years of long-acting benzodiazepine use, rebound insomnia is an issue, as well. Patients stop the medication and "boom, their sleep is worse than ever for a week or two" before normalizing. The problem can keep "patients taking these drugs for years and years," Dr. Parish said.
So it’s important to let patients know beforehand about the rebound potential, and tell them "that it’s going to be bad for a while, but don’t panic. Things will [get] better," he said.
Ramelteon, a melatonin receptor agonist, "is another useful drug." With no affinity for benzodiazepine receptors, it should not cause daytime drowsiness, he said.
Ramelteon metabolizes in the liver, so it can’t be used in patients with liver disease. It also increases concentrations of alcohol, azole antifungal drugs, and fluvoxamine, and decreases rifampin levels.
"You have to think about how it’s going to affect other drugs. Given that, I think it’s a reasonably effective, reasonably safe drug," Dr. Parish said.
Because they have anticholinergic and antihistaminic effects, some antidepressants are insomnia options, too, but not as first-line agents and at doses lower than those used for depression.
The tricyclic antidepressant doxepin (Silenor) was approved for insomnia in 2010 at 3-mg and 6-mg doses, but it cannot be used with monoamine oxidase inhibitors.
Follow-up is important with all insomnia agents to assess effect and safety and to monitor for dose escalation. Concomitant cognitive-behavioral therapies – stimulus control and sleep restriction, for example – are helpful as well, with the goal of tapering patients off sleeping pills as behavior therapy takes effect.
Dr. Parish said he had no relevant financial disclosures.