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 Mar;70(3):319-29. doi: 10.1007/s00228-013-1613-6. Epub 2013 Dec 12.

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.

MeSH terms

  • Aged
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / adverse effects*
  • Cognition / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects*
  • Psychomotor Performance / drug effects
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Reaction Time / drug effects
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Substance Withdrawal Syndrome / psychology*
  • Temazepam / administration & dosage
  • Temazepam / adverse effects*
  • Time Factors
  • Zolpidem

Substances

  • Azabicyclo Compounds
  • Hypnotics and Sedatives
  • Piperazines
  • Pyridines
  • zopiclone
  • Zolpidem
  • Temazepam