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 volume 70, pages319–329(2014)Cite this article

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.

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Author information

Affiliations

  1. Department of Family Medicine, University of Turku, Lemminkäisenkatu 1, 20014, Turku, Finland

    Juha Puustinen, Ritva Lähteenmäki, Ismo Räihä & Sirkka-Liisa Kivelä

  2. Medical Teaching and Research Health Centre, University Consortium of Pori, Pori, Finland

    Juha Puustinen & Ritva Lähteenmäki

  3. Department of Neurology, University of Turku, Turku, Finland

    Juha Puustinen

  4. Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland

    Juha Puustinen

  5. Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland

    Päivi Polo-Kantola

  6. University of Turku, Turku, Finland

    Päivi Polo-Kantola

  7. Sleep Research Unit, University of Turku, Turku, Finland

    Päivi Polo-Kantola

  8. Department of Psychology, University of Turku, Turku, Finland

    Paula Salo

  9. Research Unit for Psychosocial Factors, Finnish Institute of Occupational Health, Turku, Finland

    Paula Salo

  10. Department of Biostatistics, University of Turku, Turku, Finland

    Tero Vahlberg

  11. College of Public Affairs, University of Baltimore, Baltimore, MD, USA

    Alan Lyles

  12. Division of Social Pharmacy, University of Helsinki, Helsinki, Finland

    Alan Lyles & Sirkka-Liisa Kivelä

  13. Härkätie Health Centre, Lieto, Finland

    Alan Lyles

  14. Clinical Pharmacology, University of Helsinki, Helsinki, Finland

    Pertti J. Neuvonen

  15. HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

    Pertti J. Neuvonen

  16. Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland

    Markku Partinen

  17. Haartman Institute, University of Helsinki, Helsinki, Finland

    Markku Partinen

  18. Turku City Hospital, Turku, Finland

    Ismo Räihä

  19. Satakunta Central Hospital, Hospital District of Satakunta, Pori, Finland

    Sirkka-Liisa Kivelä

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  1. Juha Puustinen
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Puustinen, J., Lähteenmäki, R., Polo-Kantola, P. et al. Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults. Eur J Clin Pharmacol 70, 319–329 (2014). https://doi.org/10.1007/s00228-013-1613-6

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Keywords

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