Is Melatonin Helpful in Stopping the Long-Term Use of Hypnotics? A Discontinuation Trial
Open accessAbstract
OBJECTIVE: To find out if administration of melatonin facilitates discontinuation of benzodiazepine (BD) therapy in patients with insomnia. METHOD: A placebo controlled trial in nine general practices in the Netherlands. Long-term users of benzodiazepines were asked by their GP to participate in a discontinuation program in combination with melatonin or placebo. The intervention and follow-up period lasted one year. During this period participants received four questionnaires about their use of sleeping medication and several health instruments. The urine of all participants was tested for the presence of benzodiazepines, as proof of the discontinuation. MAIN OUTCOME MEASURE: The discontinuation of benzodiazepine use measured by questionnaires and urine samples at three assessment points. RESULTS: A total of 503 long-term users were selected by the GPs, of whom 38 patients (16M/22F) participated. After one year 40% had stopped their benzodiazepine use, both in the intervention group on melatonin and in the placebo control group. Comparing stoppers and non-stoppers did not reveal significant differences in benzodiazepine use, or awareness of problematic use. CONCLUSION: Our findings do not conclusively indicate that melatonin is helpful for the discontinuation of the use of benzodiazepines, but the average dose of benzodiazepines in the group was low. Further investigation is necessary, with special attention to the possible influence of the daily dose on the facilitation effect of melatonin.
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Two reviews show no added value of melatonin substitution for benzodiazepine discontinuation.
“Nevertheless, two reviews show no added value of melatonin substitution [66,67] and, to the best of our knowledge, arguments regarding the benefit of diazepam substitution are mostly theoretical (not evidence-based).”
From Cognitive behavioral therapy and acceptance and commitment therapy for the discontinuation of long-term benzodiazepine use in insomnia and anxiety disorders (2021) · cites this paper as [66]
The Results report nearly identical one-year benzodiazepine discontinuation rates with melatonin and placebo (8/20 versus 7/18), with no significant difference. But this source is a discontinuation trial, not a review, and its Abstract Conclusion says the findings are inconclusive, particularly because the participants' average benzodiazepine dose was low. It therefore supports a lack of demonstrated added benefit in this trial, not the claim that reviews establish no added value generally. (LLM, conf=0.88)
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“Nevertheless, two reviews show no added value of melatonin substitution [66,67] and, to the best of our knowledge, arguments regarding the benefit of diazepam substitution are mostly theoretical (not evidence-based).”
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- Authors
- Vissers, F. H. J. A., Knipschild, P. G., & Crebolder, H. F. J. M.
- Affiliations
- Maastricht University (NL)
- Corresponding author
- Crebolder, Harry F. J. M.
- Venue
- Pharmacy World & Science
- Published
- 2007-07-03
- Volume
- 29
- Issue
- 6
- Pages
- 641-646
- ISSN
- 0167-6555 (ISSN-L)
- 0928-1231
- 1573-739X
- PMC
- PMC2039831
- OpenAlex
- W1992643698
- Cited by
- 36
- References
- 13
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Pharmacy World & Science (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- melatonin, benzodiazepine discontinuation, hypnotics, insomnia, long-term benzodiazepine use, benzodiazepine dependence, hypnotic withdrawal
- MeSH terms
- Adult, Aged, Aged, 80 and over, Benzodiazepines, Female, Humans, Hypnotics and Sedatives, Sleep Initiation and Maintenance Disorders, Male, Melatonin, Middle Aged, Sex Characteristics
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