Evidence-Based Reviews

When patients can’t sleep: Practical guide to using and choosing hypnotic therapy

Current Psychiatry. 2003 May;2(5):40-50

References

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Some patients feel that taking zaleplon only when needed allows them to use hypnotics more sparingly. On the other hand, zaleplon’s ultrashort half-life makes it less useful for patients who have frequent episodes of sleep-interruption insomnia every night. For them, a longer elimination half-life agent such as zolpidem may be more predictably effective for the entire night.¹⁵ Short half-life hypnotics have many advantages, but they do not offer anxiolysis for patients with daytime anxiety, as the longer half-life agents do.

Tolerance and rebound. Tolerance can develop following repeated dosing with benzodiazepines—primarily triazolam—and rebound insomnia can follow abrupt discontinuation. Despite widespread concerns, neither tolerance nor rebound insomnia has been well documented. Nevertheless, both can be minimized by using benzodiazepines at the lowest effective dosages and for brief periods. Gradual tapering when discontinuing the drug can help control rebound.

Tolerance and rebound seem to be less of a concern with the newer hypnotics than with benzodiazepines. In preliminary uncontrolled trials, zolpidem and zaleplon did not show evidence of these problems in 1 year of continued use.

NONHYPNOTIC SLEEP AIDS

Sedating antidepressants. Physicians often prescribe low doses of sedating antidepressants to control insomnia, a practice supported by some controlled clinical trials. For example, polysomnography showed that patients who took doxepin, 25 to 50 mg at bedtime, had enhanced sleep efficiency (ratio of time slept to time spent in bed) yet no change in sleep latency. Liver abnormalities, leukopenia, and thrombopenia developed in a few patients.¹⁶ Controlled studies have also shown subjective efficacy of trazodone¹⁷ and trimipramine¹⁸ in treating insomnia.

Some physicians advocate using the 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.¹⁹

Although possibly helpful as sleep aids, antidepressants are also associated with side effects. Trazodone, for example, may cause daytime sedation, orthostatic hypotension, and priapism. As a class, the tricyclics are associated with anticholinergic effects such as dry mouth, urinary flow difficulties, and cardiac dysrhythmias.

Table 4

Guidelines for safe use of hypnotics

Define a clear indication and treatment goal Prescribe the lowest effective dose Individualize the dose for each patient Use lower doses with a CNS depressant or alcohol Consider dose adjustment in the elderly and in patients with hepatic or renal disease Avoid in patients with sleep apnea syndrome, pregnancy, and history of abuse Limit duration of use Consider intermittent therapy for patients who need longer-term treatment Taper doses to avoid abrupt discontinuation Re-evaluate drug treatment regularly; assess both efficacy and adverse effects

Define a clear indication and treatment goal
Prescribe the lowest effective dose
Individualize the dose for each patient
Use lower doses with a CNS depressant or alcohol
Consider dose adjustment in the elderly and in patients with hepatic or renal disease
Avoid in patients with sleep apnea syndrome, pregnancy, and history of abuse
Limit duration of use
Consider intermittent therapy for patients who need longer-term treatment
Taper doses to avoid abrupt discontinuation
Re-evaluate drug treatment regularly; assess both efficacy and adverse effects

Alcohol. Patients with insomnia often self-medicate with agents that are not specifically indicated to induce sleep. Alcohol is widely used at bedtime because it enhances sleepiness and induces a more rapid sleep onset.²⁰ Drinking a “nightcap” is a poor choice, however, because alcohol—especially after prolonged use—can impair sleep quality, resulting in daytime somnolence. Alcohol is also associated with rapid development of tolerance.

Patients who use alcohol report unrefreshing and disturbed sleep, with frequent nocturnal awakenings even after prolonged abstinence. Alcohol also can further impair sleep-related respiration in patients with obstructive sleep apnea syndrome.

Antihistamines and over-the-counter products whose main active ingredients are antihistamines—such as doxylamine and diphenhydramine—can cause unpredictable efficacy and side effects such as daytime sedation, confusion, and systemic anticholinergic effects.²¹

Melatonin is a 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, jetlag, blindness, delayed sleep phase syndrome—and in the elderly. However, melatonin’s efficacy has not been established conclusively and is in doubt. Concerns have been expressed regarding the purity of available preparations and possible coronary artery tissue stimulation, as observed in animal studies of melatonin.

Related resources

American Academy of Sleep Medicine. Sleep logs, patient education materials. www.aasmnet.org
American Sleep Apnea Association. www.sleepapnea.org
National Sleep Foundation. www.sleepfoundation.org

Drug brand names

Amitriptyline • Elavil
Bupropion • Wellbutrin
Citalopram • Celexa
Doxepin • Sinequan
Escitalopram • Lexapro
Estazolam • Prosom
Flurazepam • Dalmane
Mirtazapine • Remeron
Nefazodone • Serzone
Protriptyline • Vivactil
Quazepam • Doral
Temazepam • Restoril
Trazodone • Desyrel
Triazolam • Halcion
Trimipramine • Surmontil
Venlafaxine • Effexor
Zaleplon • Sonata
Zolpidem • Ambien

Disclosure

Dr. Doghramji receives research grant support from Cephalon Inc., GlaxoSmithKline, Merck & Co., and Sanofi-Synthelabo.