European Journal of Clinical Pharmacology

, Volume 70, Issue 3, pp 319–329 | Cite as

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

  • Juha PuustinenEmail author
  • Ritva Lähteenmäki
  • Päivi Polo-Kantola
  • Paula Salo
  • Tero Vahlberg
  • Alan Lyles
  • Pertti J. Neuvonen
  • Markku Partinen
  • Ismo Räihä
  • Sirkka-Liisa Kivelä
Pharmacoepidemiology and Prescription



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.


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.


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.


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.


Temazepam Zopiclone Zolpidem Withdrawal Cognition Long-term effects 


Acknowledgments, author contributions and competing financial interests

See ESM Acknowledgments.

Supplementary material

228_2013_1613_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 30.6 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Juha Puustinen
    • 1
    • 2
    • 3
    • 4
    Email author
  • Ritva Lähteenmäki
    • 1
    • 2
  • Päivi Polo-Kantola
    • 5
    • 6
    • 7
  • Paula Salo
    • 8
    • 9
  • Tero Vahlberg
    • 10
  • Alan Lyles
    • 11
    • 12
    • 13
  • Pertti J. Neuvonen
    • 14
    • 15
  • Markku Partinen
    • 16
    • 17
  • Ismo Räihä
    • 1
    • 18
  • Sirkka-Liisa Kivelä
    • 1
    • 12
    • 19
  1. 1.Department of Family MedicineUniversity of TurkuTurkuFinland
  2. 2.Medical Teaching and Research Health CentreUniversity Consortium of PoriPoriFinland
  3. 3.Department of NeurologyUniversity of TurkuTurkuFinland
  4. 4.Division of Clinical NeurosciencesTurku University HospitalTurkuFinland
  5. 5.Department of Obstetrics and GynecologyTurku University HospitalTurkuFinland
  6. 6.University of TurkuTurkuFinland
  7. 7.Sleep Research UnitUniversity of TurkuTurkuFinland
  8. 8.Department of PsychologyUniversity of TurkuTurkuFinland
  9. 9.Research Unit for Psychosocial FactorsFinnish Institute of Occupational HealthTurkuFinland
  10. 10.Department of BiostatisticsUniversity of TurkuTurkuFinland
  11. 11.College of Public AffairsUniversity of BaltimoreBaltimoreUSA
  12. 12.Division of Social PharmacyUniversity of HelsinkiHelsinkiFinland
  13. 13.Härkätie Health CentreLietoFinland
  14. 14.Clinical PharmacologyUniversity of HelsinkiHelsinkiFinland
  15. 15.HUSLABHelsinki University Central HospitalHelsinkiFinland
  16. 16.Helsinki Sleep ClinicVitalmed Research CenterHelsinkiFinland
  17. 17.Haartman InstituteUniversity of HelsinkiHelsinkiFinland
  18. 18.Turku City HospitalTurkuFinland
  19. 19.Satakunta Central HospitalHospital District of SatakuntaPoriFinland

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