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CHAPTER 22 Sedative-Hypnotic Drugs 391

Sedative-hypnotics should be used with appropriate caution to TABLE 22–3 Dosages of drugs used commonly for
minimize adverse effects. A dose should be prescribed that does not sedation and hypnosis.
impair mentation or motor functions during waking hours. Some
patients may tolerate the drug better if most of the daily dose is Sedation Hypnosis
given at bedtime, with smaller doses during the day. Prescriptions Dosage
should be written for short periods, since there is little justifica- Drug Dosage Drug (at Bedtime)
tion for long-term therapy (defined as use of therapeutic doses
for 2 months or longer). The physician should make an effort to Alprazolam 0.25–0.5 mg Chloral 500–1000 mg
2–3 times daily
hydrate
assess the efficacy of therapy from the patient’s subjective responses.
Combinations of antianxiety agents should be avoided, and people Buspirone 5–10 mg Estazolam 0.5–2 mg
2–3 times daily
taking sedatives should be cautioned about the consumption of Eszopiclone 1–3 mg
alcohol and the concurrent use of over-the-counter medications Chlordiazepoxide 10–20 mg
2–3 times daily
containing antihistaminic or anticholinergic drugs (see Chapter 63). Lorazepam 2–4 mg
Clorazepate 5–7.5 mg twice Quazepam 7.5–15 mg
daily
Secobarbital 100–200 mg
TREATMENT OF SLEEP PROBLEMS Diazepam 5 mg twice daily
Halazepam 20–40 mg Suvorexant 10 mg
Sleep disorders are common and often result from inadequate treat- 3–4 times daily Tasimelteon 10 mg
ment of underlying medical conditions or psychiatric illness. True Lorazepam 1–2 mg once or
primary insomnia is rare. Nonpharmacologic therapies that are twice daily Temazepam 7.5–30 mg
useful for sleep problems include proper diet and exercise, avoiding Oxazepam 15–30 mg Triazolam 0.125–0.5 mg
stimulants before retiring, ensuring a comfortable sleeping environ- 3–4 times daily Zaleplon 5–20 mg
ment, and retiring at a regular time each night. In some cases, how- Phenobarbital 15–30 mg
ever, the patient will need and should be given a sedative-hypnotic 2–3 times daily Zolpidem 2.5–10 mg
for a limited period. It should be noted that the abrupt discontinu-
ance of many drugs in this class can lead to rebound insomnia.
Benzodiazepines can cause a dose-dependent decrease in both have value in the management of patients who awaken early in
REM and slow-wave sleep, though to a lesser extent than the barbi- the sleep cycle. At recommended doses, zaleplon and eszopiclone
turates. The newer hypnotics, zolpidem, zaleplon, and eszopiclone, (despite a relatively long half-life) appear to cause less amnesia or
are less likely than the benzodiazepines to change sleep patterns. day-after somnolence than zolpidem or benzodiazepines.
However, so little is known about the clinical impact of these effects Suvorexant is FDA-approved for treatment of both sleep-onset
that statements about the desirability of a particular drug based on and sleep-maintenance insomnia. The most common adverse
its effects on sleep architecture have more theoretical than practical effect of suvorexant is next-day somnolence.
significance. Clinical criteria of efficacy in alleviating a particular The drugs in this class commonly used for sedation and hyp-
sleeping problem are more useful. The drug selected should be one nosis are listed in Table 22–3 together with recommended doses.
that provides sleep of fairly rapid onset (decreased sleep latency) and Note: The failure of insomnia to remit after 7–10 days of treat-
sufficient duration, with minimal “hangover” effects such as drowsi- ment may indicate the presence of a primary psychiatric or medi-
ness, dysphoria, and mental or motor depression the following day. cal illness that should be evaluated. Long-term use of hypnotics is
Older drugs such as chloral hydrate, secobarbital, and pentobarbital an irrational and dangerous medical practice.
continue to be used, but benzodiazepines, zolpidem, zaleplon, or
eszopiclone are generally preferred. Daytime sedation is more com-
mon with benzodiazepines that have slow elimination rates (eg, OTHER THERAPEUTIC USES
lorazepam) and those that are biotransformed to active metabolites
(eg, flurazepam, quazepam). If benzodiazepines are used nightly, Table 22–2 summarizes several other important clinical uses of
tolerance can occur, which may lead to dose increases by the patient drugs in the sedative-hypnotic class. Drugs used in the manage-
to produce the desired effect. Anterograde amnesia occurs to some ment of seizure disorders and as intravenous agents in anesthesia
degree with all benzodiazepines used for hypnosis. are discussed in Chapters 24 and 25.
Eszopiclone, zaleplon, and zolpidem have efficacies similar For sedative and possible amnestic effects during medical or
to those of the hypnotic benzodiazepines in the management of surgical procedures such as endoscopy and bronchoscopy—as
sleep disorders. Favorable clinical features of zolpidem and the well as for premedication prior to anesthesia—oral formulations
other newer hypnotics include rapid onset of activity and mod- of shorter-acting drugs are preferred.
est day-after psychomotor depression with few amnestic effects. Long-acting drugs such as chlordiazepoxide and diazepam and,
Zolpidem, one of the most frequently prescribed hypnotic drugs to a lesser extent, phenobarbital are administered in progressively
in the United States, is available in a biphasic release formulation decreasing doses to patients during withdrawal from physiologic
that provides sustained drug levels for sleep maintenance. Zaleplon dependence on ethanol or other sedative-hypnotics. Parenteral
acts rapidly, and because of its short half-life, the drug appears to lorazepam is used to suppress the symptoms of delirium tremens.