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Published in: International Journal of Clinical Pharmacy 6/2007

Open Access 01-12-2007 | Research Article

Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial

Authors: Frans H. J. A. Vissers, Paul G. Knipschild, Harry F. J. M. Crebolder

Published in: International Journal of Clinical Pharmacy | Issue 6/2007

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Abstract

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.
Literature
1.
go back to reference GIP-Signal: Use of benzodiazepines 1993–1998. Geneesmiddelen Informatie Project (GIP)/College voor zorgverzekeringen. Amstelveen, 2000. GIP-Signal: Use of benzodiazepines 1993–1998. Geneesmiddelen Informatie Project (GIP)/College voor zorgverzekeringen. Amstelveen, 2000.
2.
go back to reference Knuistingh Neven A, Graaff de WJ, Lucassen PLBJ, Springer MP, Bonsema K, Dijkstra RH. NHG-standard Insomnia and sleeping medication. Huisarts Wet 1992;35: 209–12. Knuistingh Neven A, Graaff de WJ, Lucassen PLBJ, Springer MP, Bonsema K, Dijkstra RH. NHG-standard Insomnia and sleeping medication. Huisarts Wet 1992;35: 209–12.
3.
go back to reference Cormack MA, Sweeney KG, Hughes-Jones Foot GA. Evaluation of an easy, cost effective strategy for cutting benzodiazepine use in general practice. Br J Gen Pract 1994;44:5–8.PubMed Cormack MA, Sweeney KG, Hughes-Jones Foot GA. Evaluation of an easy, cost effective strategy for cutting benzodiazepine use in general practice. Br J Gen Pract 1994;44:5–8.PubMed
4.
go back to reference Oude Voshaar RC, Gorgels WJM, Mol AJJ, et al. Treatments to discontinue long-term use of benzodiazepines. Ned Tijdschr Geneesk 2001;145:1347–50. Oude Voshaar RC, Gorgels WJM, Mol AJJ, et al. Treatments to discontinue long-term use of benzodiazepines. Ned Tijdschr Geneesk 2001;145:1347–50.
5.
go back to reference Niessen WJM, Sewart RE, Broer L, Haaijer-Ruskamp FM. Decrease of benzodiazepines of long-term users by a letter of their own GPs. Ned Tijdschr Geneeskd 2005;149 (7):356–61.PubMed Niessen WJM, Sewart RE, Broer L, Haaijer-Ruskamp FM. Decrease of benzodiazepines of long-term users by a letter of their own GPs. Ned Tijdschr Geneeskd 2005;149 (7):356–61.PubMed
6.
go back to reference Anonymus. Discontinuation of benzodiazepines. Gebu 1994;28(12):98–101. Anonymus. Discontinuation of benzodiazepines. Gebu 1994;28(12):98–101.
7.
go back to reference Oude Voshaar RC, Gorgels WJM, Mol AJJ, Balkom van AJLM, Lisdonk van de EH, Breteler MHM, Hoogen van den HJM, Zitman FG. Tapering off long-term benzodiazepine use with or without group cognitive-behavioural therapy: three-condition, randomised controlled trial. Br J Psychiatry 2003;182:498–504.CrossRef Oude Voshaar RC, Gorgels WJM, Mol AJJ, Balkom van AJLM, Lisdonk van de EH, Breteler MHM, Hoogen van den HJM, Zitman FG. Tapering off long-term benzodiazepine use with or without group cognitive-behavioural therapy: three-condition, randomised controlled trial. Br J Psychiatry 2003;182:498–504.CrossRef
8.
go back to reference Nagtegaal JE. Pharmaceutical, chronobiological and clinical aspects of melatonin. [PhD thesis] Amsterdam 2001; ISBN 90-9015249-0. Nagtegaal JE. Pharmaceutical, chronobiological and clinical aspects of melatonin. [PhD thesis] Amsterdam 2001; ISBN 90-9015249-0.
9.
go back to reference Olde Rikkert MG, Rigaud AS. Melatonin in elderly patients with insomnia. A systematic review. Z Gerontol Geriatr. 2001;34(6):491–7.PubMedCrossRef Olde Rikkert MG, Rigaud AS. Melatonin in elderly patients with insomnia. A systematic review. Z Gerontol Geriatr. 2001;34(6):491–7.PubMedCrossRef
10.
go back to reference Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin. A new clinical appraoch. Arch Intern Med 1999;159:2456–60.PubMedCrossRef Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin. A new clinical appraoch. Arch Intern Med 1999;159:2456–60.PubMedCrossRef
11.
go back to reference Cardinali DP, Gvozdenovich E, Kaplan MR, Fainstein I, Shifis HA, Perez Lloret S, Albornoz L, Negri A. A double blind-placebo controlled study on melatonin to reduce anxiolytic benzodiazepine use in the elderly. Neuro Endocrin Lett 2002;23(1):55–60. Cardinali DP, Gvozdenovich E, Kaplan MR, Fainstein I, Shifis HA, Perez Lloret S, Albornoz L, Negri A. A double blind-placebo controlled study on melatonin to reduce anxiolytic benzodiazepine use in the elderly. Neuro Endocrin Lett 2002;23(1):55–60.
12.
go back to reference Lamberts H, Wood M. ICP, International Classification of Primary Care. Oxford University Press, New York 1987. ISBN 90-5170-279-5. Lamberts H, Wood M. ICP, International Classification of Primary Care. Oxford University Press, New York 1987. ISBN 90-5170-279-5.
13.
go back to reference Diest van R, Milius H, Markusse R, Snel J. The sleep wake experience list. T Soc Gezondheidsz 1989;10:343–7. Diest van R, Milius H, Markusse R, Snel J. The sleep wake experience list. T Soc Gezondheidsz 1989;10:343–7.
14.
go back to reference Mulder-Hajonides van der Meulen WREH. The Groningen sleep quality scale. In: Proceedings of the 14th CINP congress. Florence: Italy; 1984. Mulder-Hajonides van der Meulen WREH. The Groningen sleep quality scale. In: Proceedings of the 14th CINP congress. Florence: Italy; 1984.
15.
go back to reference van der Zee KI, Sanderman R. Measuring general health with RAND-36: a manual. Groningen 1993: Noordelijk Centrum voor Gezondheidsvraagstukken, NCG. ISBN 90-72156-60-9. van der Zee KI, Sanderman R. Measuring general health with RAND-36: a manual. Groningen 1993: Noordelijk Centrum voor Gezondheidsvraagstukken, NCG. ISBN 90-72156-60-9.
16.
go back to reference Kan C. Structured appraoches to the Asessment of Benzodiazepine Dependence. The development of the Benzodiazepine Dependence Self-Report Questionnaire. [PhD thesis] Nijmegen 2000; ISBN 90-9013945-1. Kan C. Structured appraoches to the Asessment of Benzodiazepine Dependence. The development of the Benzodiazepine Dependence Self-Report Questionnaire. [PhD thesis] Nijmegen 2000; ISBN 90-9013945-1.
17.
go back to reference Benzodiazepines in urine. Cobas Integra 700, Roche Diagnostics, Mannheim, Germany. Benzodiazepines in urine. Cobas Integra 700, Roche Diagnostics, Mannheim, Germany.
18.
go back to reference Zitman FG, Couvée JE. Chronic benzodiazepine use in general practice patients with depression: an evaluation of controlled treatment and taper off. Br J Psychiatry 2001;178: 317–24.PubMedCrossRef Zitman FG, Couvée JE. Chronic benzodiazepine use in general practice patients with depression: an evaluation of controlled treatment and taper off. Br J Psychiatry 2001;178: 317–24.PubMedCrossRef
19.
go back to reference Vissers FHJA. Use of sleeping and sedative medication in daily practice. Determinants, consequences and the role of the GP. [PhD thesis] Maastricht 1998; ISBN 90-5681-047-2. Vissers FHJA. Use of sleeping and sedative medication in daily practice. Determinants, consequences and the role of the GP. [PhD thesis] Maastricht 1998; ISBN 90-5681-047-2.
20.
go back to reference Holden JD, Hughes IM, Tree A. Benzodiazepine prescribing and withdrawal for 3234 patients in 15 general practices. Fam Pract 1994;11:358–62.PubMedCrossRef Holden JD, Hughes IM, Tree A. Benzodiazepine prescribing and withdrawal for 3234 patients in 15 general practices. Fam Pract 1994;11:358–62.PubMedCrossRef
21.
go back to reference Oude Voshaar RC, Gorgels WJMJ, Mol AJJ, van Balkom AJLM, Breteler MHH, van de Lisdonk EH, Mulder J, Zitmans FG. Predictors of relapse after discontinuation of long-term benzodiazepine use by minimal intervention: 2-year follow-up study. Fam Pract 2003;20(4):370–72.CrossRef Oude Voshaar RC, Gorgels WJMJ, Mol AJJ, van Balkom AJLM, Breteler MHH, van de Lisdonk EH, Mulder J, Zitmans FG. Predictors of relapse after discontinuation of long-term benzodiazepine use by minimal intervention: 2-year follow-up study. Fam Pract 2003;20(4):370–72.CrossRef
Metadata
Title
Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial
Authors
Frans H. J. A. Vissers
Paul G. Knipschild
Harry F. J. M. Crebolder
Publication date
01-12-2007
Publisher
Springer Netherlands
Published in
International Journal of Clinical Pharmacy / Issue 6/2007
Print ISSN: 2210-7703
Electronic ISSN: 2210-7711
DOI
https://doi.org/10.1007/s11096-007-9118-y

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