Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia
Open accessAbstract
Long-term use of benzodiazepines or benzodiazepine receptor agonists is widespread, although guidelines recommend short-term use. Only few controlled studies have characterized the effect of discontinuation of their chronic use on sleep and quality of life. We studied perceived sleep and quality of life in 92 older (age 55-91 years) outpatients with primary insomnia before and after withdrawal from long-term use of zopiclone, zolpidem or temazepam (BZDA). BZDA was withdrawn during 1 month, during which the participants received psychosocial support and blindly melatonin or placebo. A questionnaire was used to study perceived sleep and quality of life before withdrawal, and 1 month and 6 months later. 89 participants completed the 6-month follow-up. As melatonin did not improve withdrawal, all participants were pooled and then separated based solely on the withdrawal results at 6 months (34 Withdrawers. 55 Nonwithdrawers) for this secondary analysis. At 6 months, the Withdrawers had significantly (P < 0.05) shorter sleep-onset latency and less difficulty in initiating sleep than at baseline and when compared to Nonwithdrawers. Compared to baseline, both Withdrawers and Nonwithdrawers had at 6 months significantly (P < 0.05) less fatigue during the morning and daytime. Stress was alleviated more in Withdrawers than in Nonwithdrawers (P < 0.05). Satisfaction with life and expected health 1 year later improved (P < 0.05) in Withdrawers. In conclusion, sleep disturbances, daytime fatigue and impaired quality of life may resolve within 6 months of BZDA withdrawal. These results encourage withdrawal from chronic use of benzodiazepine-type hypnotics, particularly in older subjects.
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Reported rates of successful discontinuation using 2 mg of prolonged-release melatonin ranged from 31 to 46.5%.
“The reported rates of successful discontinuation using 2 mg of prolonged-release melatonin ranged from 31 to 46.5%. 84 85 86”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [86]
Only one placebo-controlled trial was conducted, which did not demonstrate significant efficacy of melatonin in facilitating withdrawal.
“Among these, only one placebo-controlled trial 86 was conducted, which did not demonstrate significant efficacy of melatonin in facilitating withdrawal.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [86]
The effectiveness of extended-release melatonin as an adjunctive agent for deprescribing BZDs and Z-drugs remains controversial; some studies reported beneficial effects, others found no advantage compared to placebo.
“Its effectiveness remains controversial: while some studies 84 85 have reported beneficial effects, others 86 have found no advantage compared to placebo.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [86]
There is limited clinical evidence to confirm the efficacy of add-on pharmacological approaches for Z-drug deprescription, but expert opinion supports their use.
“Although there is limited clinical evidence 84 85 86 90 91 97 to confirm the efficacy of these approaches, expert opinion supports their use (particularly when guided by a comprehensive evaluation of patient comorbidities) as a means to facilitate Z-drug withdrawal.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [86]
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- Authors
- Lähteenmäki, R., Neuvonen, P. J., Puustinen, J., Vahlberg, T., Partinen, M., Räihä, I., & Kivelä, S.
- Affiliations
- University of Turku (FI)
- University of Helsinki (FI)
- Department of Family Medicine University of Turku Turku Finland
- Corresponding author
- Neuvonen, Pertti J.
- Venue
- Basic & Clinical Pharmacology & Toxicology
- Publisher
- Wiley
- Published
- 2018-12-03
- Volume
- 124
- Issue
- 3
- Pages
- 330-340
- ISSN
- 1742-7835 (ISSN-L)
- 1742-7843
- OpenAlex
- W2896768616
- Cited by
- 34
- References
- 28
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 1
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Basic & Clinical Pharmacology & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- UTUPub (University of Turku) (submittedVersion)
- Funders
- Suomen Kulttuurirahasto
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- benzodiazepine withdrawal, zopiclone, zolpidem, temazepam, long-term hypnotic use, primary insomnia, older adults, quality of life, sleep latency, daytime fatigue, stress, melatonin, psychosocial support
- MeSH terms
- Sleep Aids, Pharmaceutical, Zolpidem, Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Hypnotics and Sedatives, Sleep Initiation and Maintenance Disorders, Male, Melatonin, Middle Aged, Piperazines, Quality of Life, Surveys and Questionnaires, Sleep, Substance Withdrawal Syndrome, Temazepam, Azabicyclo Compounds
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