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Published in: BMC Geriatrics 1/2018

Open Access 01-12-2018 | Research Article

Long-term persistence of withdrawal of temazepam, zopiclone, and zolpidem in older adults: a 3-year follow-up study

Authors: Juha Puustinen, Ritva Lähteenmäki, Janne Nurminen, Tero Vahlberg, Pertti Aarnio, Markku Partinen, Ismo Räihä, Pertti J. Neuvonen, Sirkka-Liisa Kivelä

Published in: BMC Geriatrics | Issue 1/2018

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Abstract

Background

Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications.

Methods

92 outpatients (≥55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 ± 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records.

Results

Of the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 ± 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001).
Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result.

Conclusions

At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase.
Literature
1.
go back to reference Obiora E, Hubbard R, Sanders RD, Myles PR. The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort. Thorax. 2013;68(2):163–70.CrossRefPubMed Obiora E, Hubbard R, Sanders RD, Myles PR. The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort. Thorax. 2013;68(2):163–70.CrossRefPubMed
3.
go back to reference Park H, Satoh H, Miki A, Urushihara H, Sawada Y. Medications associated with falls in older people: systematic review of publications from a recent 5-year period. Eur J Clin Pharmacol. 2015;71(12):1429–40.CrossRefPubMed Park H, Satoh H, Miki A, Urushihara H, Sawada Y. Medications associated with falls in older people: systematic review of publications from a recent 5-year period. Eur J Clin Pharmacol. 2015;71(12):1429–40.CrossRefPubMed
4.
go back to reference By the American Geriatrics Society Beers Criteria Update Expert P. American geriatrics society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46.CrossRef By the American Geriatrics Society Beers Criteria Update Expert P. American geriatrics society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46.CrossRef
5.
go back to reference Kurko TA, Saastamoinen LK, Tahkapaa S, Tuulio-Henriksson A, Taiminen T, Tiihonen J, Airaksinen MS, Hietala J. Long-term use of benzodiazepines: definitions, prevalence and usage patterns - a systematic review of register-based studies. Eur Psychiatry. 2015;30(8):1037–47.CrossRefPubMed Kurko TA, Saastamoinen LK, Tahkapaa S, Tuulio-Henriksson A, Taiminen T, Tiihonen J, Airaksinen MS, Hietala J. Long-term use of benzodiazepines: definitions, prevalence and usage patterns - a systematic review of register-based studies. Eur Psychiatry. 2015;30(8):1037–47.CrossRefPubMed
6.
go back to reference Puustinen J, Nurminen J, Kukola M, Vahlberg T, Laine K, Kivela SL. Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly. Drugs Aging. 2007;24(12):1045–59.CrossRefPubMed Puustinen J, Nurminen J, Kukola M, Vahlberg T, Laine K, Kivela SL. Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly. Drugs Aging. 2007;24(12):1045–59.CrossRefPubMed
8.
go back to reference Hosia-Randell H, Pitkälä K. Use of psychotropic drugs in elderly nursing home residents with and without dementia in Helsinki, Finland. Drugs Aging. 2005;22(9):793–800.CrossRefPubMed Hosia-Randell H, Pitkälä K. Use of psychotropic drugs in elderly nursing home residents with and without dementia in Helsinki, Finland. Drugs Aging. 2005;22(9):793–800.CrossRefPubMed
10.
go back to reference Paquin AM, Zimmerman K, Rudolph JL. Risk versus risk: a review of benzodiazepine reduction in older adults. Expert Opin Drug Saf. 2014;13(7):919–34.CrossRefPubMed Paquin AM, Zimmerman K, Rudolph JL. Risk versus risk: a review of benzodiazepine reduction in older adults. Expert Opin Drug Saf. 2014;13(7):919–34.CrossRefPubMed
11.
go back to reference Gould RL, Coulson MC, Patel N, Highton-Williamson E, Howard RJ. Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials. Br J Psychiatry. 2014;204(2):98–107.CrossRefPubMed Gould RL, Coulson MC, Patel N, Highton-Williamson E, Howard RJ. Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials. Br J Psychiatry. 2014;204(2):98–107.CrossRefPubMed
12.
go back to reference Curran HV, Collins R, Fletcher S, Kee SC, Woods B, Iliffe S. Older adults and withdrawal from benzodiazepine hypnotics in general practice: effects on cognitive function, sleep, mood and quality of life. Psychol Med. 2003;33(7):1223–37.CrossRefPubMed Curran HV, Collins R, Fletcher S, Kee SC, Woods B, Iliffe S. Older adults and withdrawal from benzodiazepine hypnotics in general practice: effects on cognitive function, sleep, mood and quality of life. Psychol Med. 2003;33(7):1223–37.CrossRefPubMed
13.
go back to reference Salzman C. The benzodiazepine controversy: therapeutic effects versus dependence, withdrawal, and toxicity. Harv Rev Psychiatry. 1997;4(5):279–82.CrossRefPubMed Salzman C. The benzodiazepine controversy: therapeutic effects versus dependence, withdrawal, and toxicity. Harv Rev Psychiatry. 1997;4(5):279–82.CrossRefPubMed
14.
go back to reference Morin CM, Belanger L, Bastien C, Vallieres A. Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse. Behav Res Ther. 2005;43(1):1–14.CrossRefPubMed Morin CM, Belanger L, Bastien C, Vallieres A. Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse. Behav Res Ther. 2005;43(1):1–14.CrossRefPubMed
16.
go back to reference Lahteenmaki R, Puustinen J, Vahlberg T, Lyles A, Neuvonen PJ, Partinen M, Raiha I, Kivela SL. Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial. Br J Clin Pharmacol. 2014;77(6):975–85.CrossRefPubMed Lahteenmaki R, Puustinen J, Vahlberg T, Lyles A, Neuvonen PJ, Partinen M, Raiha I, Kivela SL. Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial. Br J Clin Pharmacol. 2014;77(6):975–85.CrossRefPubMed
17.
go back to reference Nurminen J, Puustinen J, Lahteenmaki R, Vahlberg T, Lyles A, Partinen M, Raiha I, Neuvonen PJ, Kivela SL. Handgrip strength and balance in older adults following withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotics. BMC Geriatr. 2014;14:121.CrossRefPubMedPubMedCentral Nurminen J, Puustinen J, Lahteenmaki R, Vahlberg T, Lyles A, Partinen M, Raiha I, Neuvonen PJ, Kivela SL. Handgrip strength and balance in older adults following withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotics. BMC Geriatr. 2014;14:121.CrossRefPubMedPubMedCentral
18.
go back to reference Puustinen J, Lahteenmaki R, Polo-Kantola P, Salo P, Vahlberg T, Lyles A, Neuvonen PJ, Partinen M, Raiha I, Kivela SL. Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults. Eur J Clin Pharmacol. 2014;70(3):319–29.CrossRefPubMed Puustinen J, Lahteenmaki R, Polo-Kantola P, Salo P, Vahlberg T, Lyles A, Neuvonen PJ, Partinen M, Raiha I, Kivela SL. Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults. Eur J Clin Pharmacol. 2014;70(3):319–29.CrossRefPubMed
19.
go back to reference APA. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994. APA. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
20.
go back to reference Almeida OP, Almeida SA. Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV. Int J Geriatr Psychiatry. 1999;14(10):858–65.CrossRefPubMed Almeida OP, Almeida SA. Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV. Int J Geriatr Psychiatry. 1999;14(10):858–65.CrossRefPubMed
21.
go back to reference National Agency of Medicines. Classification of Medicines (ATC) and Defined Daily Doses (DDD). Helsinki: National Agency for Medicines; 1996. National Agency of Medicines. Classification of Medicines (ATC) and Defined Daily Doses (DDD). Helsinki: National Agency for Medicines; 1996.
22.
go back to reference Puustinen J, Nurminen J, Lopponen M, Vahlberg T, Isoaho R, Raiha I, Kivela SL. Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study. BMC Geriatr. 2011;11:70.CrossRefPubMedPubMedCentral Puustinen J, Nurminen J, Lopponen M, Vahlberg T, Isoaho R, Raiha I, Kivela SL. Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study. BMC Geriatr. 2011;11:70.CrossRefPubMedPubMedCentral
25.
go back to reference Lichstein KL, Nau SD, Wilson NM, Aguillard RN, Lester KW, Bush AJ, McCrae CS. Psychological treatment of hypnotic-dependent insomnia in a primarily older adult sample. Behav Res Ther. 2013;51:78–96.CrossRef Lichstein KL, Nau SD, Wilson NM, Aguillard RN, Lester KW, Bush AJ, McCrae CS. Psychological treatment of hypnotic-dependent insomnia in a primarily older adult sample. Behav Res Ther. 2013;51:78–96.CrossRef
26.
go back to reference Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN. Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ. 2012;17(345):e8343. https://doi.org/10.1136/bmj.e8343.CrossRef Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN. Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ. 2012;17(345):e8343. https://​doi.​org/​10.​1136/​bmj.​e8343.CrossRef
27.
go back to reference Wright A, Diebold J, Otal J, Stoneman C, Wong J, Wallace C, Duffett M. The effect of melatonin on benzodiazepine discontinuation and sleep quality in adults attempting to discontinue benzodiazepines: a systematic review and meta-analysis. Drugs Aging. 2015;32(12):1009–18.CrossRefPubMed Wright A, Diebold J, Otal J, Stoneman C, Wong J, Wallace C, Duffett M. The effect of melatonin on benzodiazepine discontinuation and sleep quality in adults attempting to discontinue benzodiazepines: a systematic review and meta-analysis. Drugs Aging. 2015;32(12):1009–18.CrossRefPubMed
Metadata
Title
Long-term persistence of withdrawal of temazepam, zopiclone, and zolpidem in older adults: a 3-year follow-up study
Authors
Juha Puustinen
Ritva Lähteenmäki
Janne Nurminen
Tero Vahlberg
Pertti Aarnio
Markku Partinen
Ismo Räihä
Pertti J. Neuvonen
Sirkka-Liisa Kivelä
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2018
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-018-0829-9

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