Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines

Anthony Kales, Rocco L. Manfredi, Alexandros N. Vgontzas, Edward O. Bixler, Antonio Vela-Bueno, Eric C. Fee

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


In three parallel groups, brief and intermittent administration and withdrawal of triazolam, 0.5 mg, temazepam, 30 mg, and placebo were assessed in a 12-night sleep laboratory study of 18 subjects with insomnia. With this intermittent schedule both drugs improved sleep, with about a one-third reduction in total wake time; this reduction was significant for temazepam but not for triazolam. Even though the periods of drug administration were quite brief, withdrawal of triazolam consistently produced rebound insomnia, with increases in total wake time above baseline of 61% and 51%, respectively, for the first night of each withdrawal period. With temazepam this effect was more variable, with total wake time increased only with the second withdrawal period (39%). Thus these findings indicate that even under conditions of brief, intermittent use and withdrawal, triazolam and, to a lesser degree, temazepam produce rebound insomnia after abrupt withdrawal, thereby predisposing to drug-taking behavior and increasing the potential for drug dependence.

Original languageEnglish (US)
Pages (from-to)468-476
Number of pages9
JournalClinical pharmacology and therapeutics
Issue number4
StatePublished - 1991

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)


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