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

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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Correspondence to 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