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

Kales, Anthony; Manfredi, Rocco L.; Vgontzas, AN; Bixler, Edward O.; Vela‐Bueno, Antonio; Fee, Eric C.

doi:10.1038/clpt.1991.55

Cited by 78 publications

(38 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This lack of significant side effects is consistent with our findings from our three previous sleep laboratory studies with temazepam [15][16][17][18] as well as studies by other investigators [19,20].…”

Section: Discussionsupporting

confidence: 83%

Temazepam 7.5 mg: effects on sleep in elderly insomniacs

Vgontzas

Kales

Bixler

et al. 1994

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Temazepam, 7.5 mg was evaluated in the sleep laboratory in 8 elderly insomniacs, using a 14-night protocol (4 placebo-baseline nights, 7 drug nights, and 3 placebo-withdrawal nights). With short-term use temazepam was found to be effective, producing a significant improvement in total wake time from baseline (100 vs. 145 min). With continued drug administration, total wake time remained below baseline but not significantly so (125 vs. 145 min). During drug administration, there were no major CNS and behavioral adverse effects reported such as daytime sedation, memory impairment or hyperexcitability (daytime anxiety). Following drug withdrawal, there was no significant increase in wakefulness, i.e., no rebound insomnia (150 vs. 145 min). In summary, temazepam, 7.5 mg is effective in elderly subjects with short-term use and has a minimum of adverse effects. Use of hypnotic drugs is an adjunctive therapy which should be for a short-term period with subsequent short-term intermittent use as needed. Because of its low propensity for producing rebound insomnia, temazepam can be effectively used in this manner.

show abstract

Section: Discussionsupporting

confidence: 83%

Temazepam 7.5 mg: effects on sleep in elderly insomniacs

Vgontzas

Kales

Bixler

et al. 1994

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…One study [96] showed that triazolam is associated with rebound in somnia even after a single night's dose. In another study [97], triazolam and, to a much lesser degree, temazepam produced rebound insomnia after only 1 or 2 nights of adminis tration. This side effect makes intermittent use, which is the most preferred form of treat ment for insomniacs, of rapidly eliminated hypnotics problematic, as it predisposes to drug-taking behavior and increases the poten tial for drug dependence [97], 210 Vgontzas/Kales/Bixlcr M echanism s o f Benzodiazepine Side Effects…”

Section: Withdrawal Phenomena (Rebound Insomnia and Anxiety)mentioning

confidence: 99%

Benzodiazepine Side Effects: Role of Pharmacokinetics and Pharmacodynamics

Vgontzas

Kales

Bixler³

1995

Pharmacology

Self Cite

103

View full text Add to dashboard Cite

Benzodiazepines have a wide variety of indications. However, CNS and psychiatric adverse reactions, tolerance, and withdrawal effects of benzodiazepines are becoming increasingly recognized and must be better understood for proper drug use. Certain benzodiazepines are associated with memory impairment and other cognitive defects and hyperexcitability phenomena during treatment (early-morning insomnia, daytime anxiety) and following withdrawal (rebound insomnia and anxiety, seizures). Elimination half-life, receptor-binding affinity, effects on the locus coeruleus-norepinephrine (LC-NE) and hypothalamic-pituitary-adrenal (HPA) axes, and the interaction of these factors appear to be major determinants of frequency and severity of these untoward effects. Rapid drug elimination and high receptor-binding affinity were initially suggested as primary underlying factors which determine frequency, severity, and type of the side effects of benzodiazepines during administration and withdrawal. Newer data and information on triazolobenzodiazepines indicate that these psychiatric adverse reactions also relate to whether the benzodiazepine has strong direct effects on the LC-NE and HPA systems. Initial suppression of the LC-NE and HPA systems is followed, on an interdose basis, by a significant rebound and activation. This repetitive pattern of suppression followed by rebound results in a neurophysiologic and behavioral sensitization (kindling) of the limbic system and consequently contributes to central nervous system and psychiatric adverse reactions. The tendency of certain of these side effects to worsen over time supports empirically this neurophysiologic and biochemical model.

show abstract

“…It is of interest that the group that had the most alcohol withdrawal rebound in the present study (lorazepam-treated multiple detoxification patients) also had the most drinking during this period. Rebound symptoms with benzodiazepines have been reported in other conditions, such as the short-term treatment of insomnia 43 and anxiety disorders. 44 It could be argued that the use of a longer-acting benzodiazepine for alcohol withdrawal might well prevent the problem of rebound symptoms.…”

Section: Discussionmentioning

confidence: 99%