Sedative-hypnotics available in the USA: zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta)

There are currently three nonbenzodiazepine sedative-hypnotics available in the United States: zolpidem (Ambien, Stilnox), zaleplon (Sonata), and eszopiclone (Lunesta). All three display an identical mechanism of action by binding to the omega-1 receptor subunit of the benzodiazepine receptor complex. They are termed “nonbenzodiazepines” as they are structurally unrelated to the benzodiazepines and do not possess the muscle relaxation properties of the benzodiazepines. Perhaps due to their lack of muscle relaxant properties or their receptor selectivity, they are thought to possess markedly lower abuse potential. This does not mean that they can be prescribed without any concern for abuse, because if dosed high enough, their effects become benzodiazepine-like. Each of these medications, like the benzodiazepines, is considered to be a controlled substance by the federal Drug Enforcement Agency (DEA).

One principal difference between the medications is half-life, that is, the time required to metabolize 50% of the compound present in the body. Zolpidem has a half-life of 1.4–4.5 hours, zaleplon has a half-life of 0.9–1.1 hours, and eszopiclone has a half-life of about 6 hours. The key is the markedly shorter half-lives that are displayed by many other sedative-hypnotics, as shown in Figure 9.1. Only eszopiclone has been shown effective for the long-term (up to 6 months) treatment of chronic insomnia.

Zolpidem is often effective at doses of 5 or 10 mg per night. Similarly, zaleplon is usually dosed at 10 mg just before bedtime (5 mg for medically ill or geriatric patients). Due to the short half-life of zaleplon, some clinicians use it to treat the occasional middle of the night awakening if there is at least 4 hours remaining until awakening. Eszopiclone is administered at doses of 2 or 3 mg at bedtime (1 or 2 mg
for elderly patients). These agents have fewer effects on sleep architecture than the benzodiazepines and little hangover effect.