Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults

Juha Puustinen, Ritva Lähteenmäki, Päivi Polo-Kantola, Paula Salo, Tero Vahlberg, Alan Lyles, Pertti J. Neuvonen, Markku Partinen, Ismo Räihä, Sirkka Liisa Kivelä

Research output: Contribution to journalArticle

Abstract

Purpose: The aim of this study was to assess the effect of withdrawal from the long-term use of temazepam, zopiclone or zolpidem as hypnotics drugs (here referred to as BZD) on cognitive performance. Methods: Ninety-two adults (age ≥55 years) with primary insomnia and who were long-term daily users of BZD volunteered to participate in a 1-month medically supported withdrawal attempt from BZD use, with a subsequent 5-month follow-up. Withdrawal was based on plasma BZD measurements at baseline, at 1 month and during subsequent regular clinical appointments. Attention and psychomotor performance were measured using the CogniSpeed® at baseline and at 1, 2 and 6 months. Reaction times were determined in the Simple Reaction Time (SRT), Two-Choice Reaction Time (2-CRT) and Vigilance tests, and errors were measured by the 2-CRT and Vigilance tests. The cognition data of the withdrawal group were also compared with a cohort of BZD non-users. Results: Eighty-nine (97 %) participants (59 women, 30 men) were followed-up for a maximum of 6 months. During the follow-up period, changes in reaction times and errors did not differ between short-term withdrawers (no residual BZD at 1 month; N = 69), non-withdrawers (residual BZD at 1 month; N = 20) or long-term withdrawers (N = 34). Compared to the reaction times of the BZD-free cohort, those of BZD users were slower at baseline. The reaction times of BZD withdrawers based on the results of the SRT or 2-CRT tests during follow-up did not reach those of the BZD-free cohort, but there was no difference between these groups in the Vigilance test. Conclusions: Long-term use of BDZ as hypnotic drugs by older adults is related to prolonged impairment of attentional and psychomotor cognitive functioning that persists for at least 6 months after withdrawal.

Original languageEnglish (US)
Pages (from-to)319-329
Number of pages11
JournalEuropean Journal of Clinical Pharmacology
Volume70
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

Fingerprint

zopiclone
Temazepam
Hypnotics and Sedatives
Cognition
Reaction Time
Psychomotor Disorders
Psychomotor Performance
Sleep Initiation and Maintenance Disorders
zolpidem
Pharmaceutical Preparations

Keywords

  • Cognition
  • Long-term effects
  • Temazepam
  • Withdrawal
  • Zolpidem
  • Zopiclone

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults. / Puustinen, Juha; Lähteenmäki, Ritva; Polo-Kantola, Päivi; Salo, Paula; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J.; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka Liisa.

In: European Journal of Clinical Pharmacology, Vol. 70, No. 3, 03.2014, p. 319-329.

Research output: Contribution to journalArticle

Puustinen, J, Lähteenmäki, R, Polo-Kantola, P, Salo, P, Vahlberg, T, Lyles, A, Neuvonen, PJ, Partinen, M, Räihä, I & Kivelä, SL 2014, 'Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults', European Journal of Clinical Pharmacology, vol. 70, no. 3, pp. 319-329. https://doi.org/10.1007/s00228-013-1613-6
Puustinen, Juha ; Lähteenmäki, Ritva ; Polo-Kantola, Päivi ; Salo, Paula ; Vahlberg, Tero ; Lyles, Alan ; Neuvonen, Pertti J. ; Partinen, Markku ; Räihä, Ismo ; Kivelä, Sirkka Liisa. / Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults. In: European Journal of Clinical Pharmacology. 2014 ; Vol. 70, No. 3. pp. 319-329.
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abstract = "Purpose: The aim of this study was to assess the effect of withdrawal from the long-term use of temazepam, zopiclone or zolpidem as hypnotics drugs (here referred to as BZD) on cognitive performance. Methods: Ninety-two adults (age ≥55 years) with primary insomnia and who were long-term daily users of BZD volunteered to participate in a 1-month medically supported withdrawal attempt from BZD use, with a subsequent 5-month follow-up. Withdrawal was based on plasma BZD measurements at baseline, at 1 month and during subsequent regular clinical appointments. Attention and psychomotor performance were measured using the CogniSpeed{\circledR} at baseline and at 1, 2 and 6 months. Reaction times were determined in the Simple Reaction Time (SRT), Two-Choice Reaction Time (2-CRT) and Vigilance tests, and errors were measured by the 2-CRT and Vigilance tests. The cognition data of the withdrawal group were also compared with a cohort of BZD non-users. Results: Eighty-nine (97 {\%}) participants (59 women, 30 men) were followed-up for a maximum of 6 months. During the follow-up period, changes in reaction times and errors did not differ between short-term withdrawers (no residual BZD at 1 month; N = 69), non-withdrawers (residual BZD at 1 month; N = 20) or long-term withdrawers (N = 34). Compared to the reaction times of the BZD-free cohort, those of BZD users were slower at baseline. The reaction times of BZD withdrawers based on the results of the SRT or 2-CRT tests during follow-up did not reach those of the BZD-free cohort, but there was no difference between these groups in the Vigilance test. Conclusions: Long-term use of BDZ as hypnotic drugs by older adults is related to prolonged impairment of attentional and psychomotor cognitive functioning that persists for at least 6 months after withdrawal.",
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AU - Puustinen, Juha

AU - Lähteenmäki, Ritva

AU - Polo-Kantola, Päivi

AU - Salo, Paula

AU - Vahlberg, Tero

AU - Lyles, Alan

AU - Neuvonen, Pertti J.

AU - Partinen, Markku

AU - Räihä, Ismo

AU - Kivelä, Sirkka Liisa

PY - 2014/3

Y1 - 2014/3

N2 - Purpose: The aim of this study was to assess the effect of withdrawal from the long-term use of temazepam, zopiclone or zolpidem as hypnotics drugs (here referred to as BZD) on cognitive performance. Methods: Ninety-two adults (age ≥55 years) with primary insomnia and who were long-term daily users of BZD volunteered to participate in a 1-month medically supported withdrawal attempt from BZD use, with a subsequent 5-month follow-up. Withdrawal was based on plasma BZD measurements at baseline, at 1 month and during subsequent regular clinical appointments. Attention and psychomotor performance were measured using the CogniSpeed® at baseline and at 1, 2 and 6 months. Reaction times were determined in the Simple Reaction Time (SRT), Two-Choice Reaction Time (2-CRT) and Vigilance tests, and errors were measured by the 2-CRT and Vigilance tests. The cognition data of the withdrawal group were also compared with a cohort of BZD non-users. Results: Eighty-nine (97 %) participants (59 women, 30 men) were followed-up for a maximum of 6 months. During the follow-up period, changes in reaction times and errors did not differ between short-term withdrawers (no residual BZD at 1 month; N = 69), non-withdrawers (residual BZD at 1 month; N = 20) or long-term withdrawers (N = 34). Compared to the reaction times of the BZD-free cohort, those of BZD users were slower at baseline. The reaction times of BZD withdrawers based on the results of the SRT or 2-CRT tests during follow-up did not reach those of the BZD-free cohort, but there was no difference between these groups in the Vigilance test. Conclusions: Long-term use of BDZ as hypnotic drugs by older adults is related to prolonged impairment of attentional and psychomotor cognitive functioning that persists for at least 6 months after withdrawal.

AB - Purpose: The aim of this study was to assess the effect of withdrawal from the long-term use of temazepam, zopiclone or zolpidem as hypnotics drugs (here referred to as BZD) on cognitive performance. Methods: Ninety-two adults (age ≥55 years) with primary insomnia and who were long-term daily users of BZD volunteered to participate in a 1-month medically supported withdrawal attempt from BZD use, with a subsequent 5-month follow-up. Withdrawal was based on plasma BZD measurements at baseline, at 1 month and during subsequent regular clinical appointments. Attention and psychomotor performance were measured using the CogniSpeed® at baseline and at 1, 2 and 6 months. Reaction times were determined in the Simple Reaction Time (SRT), Two-Choice Reaction Time (2-CRT) and Vigilance tests, and errors were measured by the 2-CRT and Vigilance tests. The cognition data of the withdrawal group were also compared with a cohort of BZD non-users. Results: Eighty-nine (97 %) participants (59 women, 30 men) were followed-up for a maximum of 6 months. During the follow-up period, changes in reaction times and errors did not differ between short-term withdrawers (no residual BZD at 1 month; N = 69), non-withdrawers (residual BZD at 1 month; N = 20) or long-term withdrawers (N = 34). Compared to the reaction times of the BZD-free cohort, those of BZD users were slower at baseline. The reaction times of BZD withdrawers based on the results of the SRT or 2-CRT tests during follow-up did not reach those of the BZD-free cohort, but there was no difference between these groups in the Vigilance test. Conclusions: Long-term use of BDZ as hypnotic drugs by older adults is related to prolonged impairment of attentional and psychomotor cognitive functioning that persists for at least 6 months after withdrawal.

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KW - Long-term effects

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KW - Withdrawal

KW - Zolpidem

KW - Zopiclone

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