Effect of Gradual Withdrawal on the Rebound Sleep Disorder after Discontinuation of Triazolam
Abstract
Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.
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Rebound anxiety can occur during ongoing treatment with rapidly eliminated benzodiazepines when their pharmacological effects decrease.
“Rebound anxiety can also occur during ongoing treatment with rapidly eliminated benzodiazepines when their pharmacological effects decrease.”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [71]
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- Authors
- Greenblatt, D. J., Harmatz, J. S., Zinny, M. A., & Shader, R. I.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1987-09-17
- Volume
- 317
- Issue
- 12
- Pages
- 722-728
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2326818216
- Cited by
- 96
- References
- 54
- Citations by year
- 2026: 2 · 2023: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2013: 1 · 2012: 1
- FWCI
- 13.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-00106)
- National Institute of Mental Health (MH 34223)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- triazolam, benzodiazepine withdrawal, medication tapering, abrupt discontinuation, insomnia, sleep latency, sleep duration, nocturnal awakenings, plasma drug concentration
- MeSH terms
- Adult, Clinical Trials as Topic, Double-Blind Method, Drug Administration Schedule, Female, Humans, Sleep Initiation and Maintenance Disorders, Male, Middle Aged, Random Allocation, Substance Withdrawal Syndrome, Triazolam
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