Correspondence

Insomnia

N Engl J Med 1997; 336:1919-1920June 26, 1997

Article

To the Editor:

In the excellent review of the management of insomnia by Kupfer and Reynolds (Jan. 30 issue),1 we read that “zolpidem may be less likely than benzodiazepines . . . to cause cognitive and psychomotor side effects (and may have fewer withdrawal effects).” It is clear that many clinicians believe this to be true, since zolpidem is the most commonly prescribed hypnotic agent in the United States.2 However, the authors cite only three studies in support of this idea, two of which did not even compare zolpidem with a benzodiazepine.

The study that did compare these drugs with respect to rebound insomnia and withdrawal used a dose of triazolam that is now considered excessive, with twice the hypnotic potency of the zolpidem dose (0.5 mg of triazolam vs. 10 mg of zolpidem).3 Nonetheless, little or no clinically significant difference was observed between the drugs in this study, and rebound insomnia occurred only after the first night of triazolam withdrawal.

Several well-designed studies have directly compared zolpidem and triazolam and have failed to show a difference in cognitive and psychomotor effects between the two drugs. The authors generally conclude that the cognitive and performance-impairing effects are remarkably similar, that they are linked directly to hypnotic potency, and that no clinically significant difference exists at the usually recommended, equipotent doses of these agents. Our conclusion from the available data is that zolpidem has no clinically important advantage over benzodiazepines (specifically, triazolam) with respect to the potential to cause cognitive, psychomotor, or withdrawal effects.

Bob L. Lobo, Pharm.D.
William L. Greene, Pharm.D.
Methodist Hospitals of Memphis, Memphis, TN 38104

5 References

1
Kupfer DJ, Reynolds CF III. Management of insomnia. N Engl J Med 1997;336:341-346
Full Text | Web of Science | Medline

2
Top 200 drugs of 1995. Pharmacy Times. April 1996:27-36.

3
Monti JM, Attali P, Monti D, Zipfel A, de la Giclais B, Morselli PL. Zolpidem and rebound insomnia -- a double-blind, controlled polysomnographic study in chronic insomniac patients. Pharmacopsychiatry 1994;27:166-175
CrossRef | Web of Science | Medline

4
Greenblatt DJ, Harmatz JS, Wright CE, Harrel L, Shader RI. Does zolpidem have unique clinical properties? A pharmacodynamic comparison with triazolam and placebo. Clin Pharmacol Ther 1996;59:178-178 abstract.

5
Wesensten NJ, Balkin TJ, Belenky GL. Effects of daytime administration of zolpidem and triazolam on performance. Aviat Space Environ Med 1996;67:115-120
Web of Science | Medline

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