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A Potential Hazard Following Withdrawal of Certain Benzodiazepines

Anthony Kales, MD; Martin B. Scharf, PhD; Joyce D. Kales, MD; Constantin R. Soldatos, MD

JAMA. 1979;241(16):1692-1695.

Abstract
Five benzodiazepine drugs (diazepam, flunitrazepam, flurazepam hydrochloride, nitrazepam, and triazolam) were evaluated separately in 15 sleep laboratory studies. Rebound insomnia, a worsening of sleep compared with baseline, occurred following withdrawal of triazolam, nitrazepam, and flunitrazepam after they had been given in only single, nightly doses for short periods. The rebound insomnia was attributed to the short and intermediate half-lives of these drugs. Diazepam and flurazepam, which have longer half-lives, did not cause rebound insomnia on withdrawal. Rebound insomnia may play a role in the development of hypnotic drug dependence with shorter-acting benzodiazepine drugs.

(JAMA 241:1692-1695, 1979)

Author Affiliations
From the Sleep Research and Treatment Center and the Departments of Psychiatry (Drs A. Kales, Scharf, J. Kales, and Soldatos) and Pharmacology (Dr Scharf), Pennsylvania State University College of Medicine, Hershey.

Footnotes
Reprint requests to Department of Psychiatry, Sleep Research and Treatment Center, The Milton S. Hershey Medical Center, Hershey, PA 17033 (Dr A. Kales).

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