When patients can’t sleep
Updated guide to workup and hypnotic therapy
Tolerance and rebound seem to be less of a concern with the newer hypnotics than with benzodiazepines, as shown by controlled studies of eszopiclone19, zolpidem23, and zaleplon.24 However, periodic re-evaluation is still the prudent clinical standard for hypnotics prescribed over long periods of time.
Table 3
Actions and available doses of common hypnotics
| Class/drug | Onset of action | Half-life (hrs) | Active metabolites | Doses (mg) |
|---|---|---|---|---|
| Benzodiazepines | ||||
| Flurazepam | Rapid | 40 to 250 | Yes | 15, 30 |
| Quazepam | Rapid | 40 to 250 | Yes | 7.5, 15 |
| Estazolam | Rapid | 10 to 24 | Yes | 0.5, 1, 2 |
| Temazepam | Intermediate | 8 to 22 | No | 7.5, 15 |
| Triazolam | Rapid | No | 0.125, 0.25, 0.5 | |
| Imidazopyridine | ||||
| Zolpidem | Rapid | 2.5 | No | 5, 10 |
| Zolpidem ER | Rapid | 2.5 | No | 6.25, 12.5 |
| Pyrazolopyrimidines | ||||
| Zaleplon | Rapid | 1 | No | 5, 10, 20 |
| Cyclopyrrolone | ||||
| Eszopiclone | Rapid | 6 | Minor | 2,3 |
| Melatonin receptor agonist | ||||
| Ramelteon | Rapid | 1 to 2.6 | No | 8 |
Guidelines for safe use of hypnotics
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Nonhypnotic Sleep AIDS
Sedating antidepressants. Some physicians prescribe low doses of sedating antidepressants to control insomnia, a practice supported by controlled clinical trials of some tricyclic antidepressants (TCAs) such as doxepin,25 trazodone,26 and trimipramine.27 Some physicians also advocate using more-sedating antidepressants—at dosages needed to treat depression—to control insomnia in depressed patients.
Evening dosing can minimize daytime sedation. If you choose an activating antidepressant, the potential side effect of insomnia can be managed by judicious use of hypnotic agents. Little is known about antidepressants’ effects on sleep quality after the first 6 to 8 weeks of treatment.28
Although possibly helpful as sleep aids, TCAs are associated with anticholinergic effects such as dry mouth, urinary flow difficulties, and cardiac dysrhythmias.
Alcohol. Patients with insomnia sometimes selfmedicate with alcohol at bedtime because it enhances sleepiness and induces a more rapid sleep onset.29 Drinking a “nightcap” is a poor choice, however, because alcohol can impair sleep quality, resulting in daytime somnolence. Alcohol is also associated with rapid development of tolerance.
Antihistamines and over-the-counter products whose main active ingredients are antihistamines—such as doxylamine and diphenhydramine—are used for insomnia and may help individuals fall asleep and stay asleep. However, antihistamine use is complicated by unpredictable efficacy and side effects such as daytime sedation, confusion, and systemic anticholinergic effects.30
Melatonin is a nonprescription dietary supplement used in dosages of 0.5 to 3,000 mg. Anecdotal reports indicate it may be efficacious in certain subtypes of insomnia—such as shift work, jet lag, blindness, delayed sleep phase syndrome—and in older patients with sleep complaints.
Melatonin’s efficacy has not been established conclusively, however, and concerns have been expressed regarding the purity of over-the-counter preparations and possible coronary artery tissue stimulation, as observed in animal studies.
Related resources
- American Academy of Sleep Medicine. Sleep logs, patient education materials. www.aasmnet.org
- American Sleep Apnea Association. National Sleep Foundation. www.sleepapnea.org
- Doxepin • Inequan
- Estazolam • Prosom
- Eszopiclone • Lunesta
- Flurazepam • Dalmane
- Quazepam • Doral
- Ramelteon • Rozerem
- Temazepam • Restoril
- Trazodone • Desyrel
- Triazolam • Halcion
- Trimipramine • Surmontil
- Zaleplon • Sonata
- Zolpidem • Ambien
Dr. Doghramji receives research grant support from Cephalon, GlaxoSmithKline, Merck & Co., and Sanofi-Synthelabo
