Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia.

Long-term use of benzodiazepines or benzodiazepine receptor agonists is widespread, although guidelines recommend short-term use. Only few controlled studies have characterized the effect of discontinuation of their chronic use on sleep and quality of life. We studied perceived sleep and quality of life in 92 older (age 55-91 years) outpatients with primary insomnia before and after withdrawal from long-term use of zopiclone, zolpidem or temazepam (BZDA). BZDA was withdrawn during 1 month, during which the participants received psychosocial support and blindly melatonin or placebo. A questionnaire was used to study perceived sleep and quality of life before withdrawal, and 1 month and 6 months later. 89 participants completed the 6-month follow-up. As melatonin did not improve withdrawal, all participants were pooled and then separated based solely on the withdrawal results at 6 months (34 Withdrawers. 55 Nonwithdrawers) for this secondary analysis. At 6 months, the Withdrawers had significantly (P < 0.05) shorter sleep-onset latency and less difficulty in initiating sleep than at baseline and when compared to Nonwithdrawers. Compared to baseline, both Withdrawers and Nonwithdrawers had at 6 months significantly (P < 0.05) less fatigue during the morning and daytime. Stress was alleviated more in Withdrawers than in Nonwithdrawers (P < 0.05). Satisfaction with life and expected health 1 year later improved (P < 0.05) in Withdrawers. In conclusion, sleep disturbances, daytime fatigue and impaired quality of life may resolve within 6 months of BZDA withdrawal. These results encourage withdrawal from chronic use of benzodiazepine-type hypnotics, particularly in older subjects.

Long-term persistence of withdrawal of temazepam, zopiclone, and zolpidem in older adults: a 3-year follow-up study.

BACKGROUND: Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications. METHODS: 92 outpatients (≥55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 ± 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records. RESULTS: Of the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 ± 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001). Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result. CONCLUSIONS: At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase.

Handgrip strength and balance in older adults following withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotics.

BACKGROUND: Benzodiazepines and related drugs affect physical functioning negatively and increase fall and fracture risk. As impaired muscle strength and balance are risk factors for falls, we examined the effects of hypnotic withdrawal on handgrip strength and balance in older adult outpatients during and after long-term use of temazepam, zopiclone and zolpidem (here collectively referred to as "benzodiazepines"). METHODS: Eighty-nine chronic users (59 women, 30 men) of temazepam, zopiclone or zolpidem aged ≥55 years participated in a benzodiazepine withdrawal study. Individual physician-directed withdrawal was performed gradually over a one-month period and participants were followed up to six months. Handgrip strength was assessed using a handheld dynamometer, and balance using the Short Berg's Balance Scale during the period of benzodiazepine use (baseline), and at 1, 2, 3 weeks, and 1, 2 and 6 months after initiating withdrawal. Withdrawal outcome and persistence were determined by plasma benzodiazepine-determinations at baseline and at four weeks ("short-term withdrawers", n = 69; "short-term non-withdrawers", n = 20), and by interviews at six months ("long-term withdrawers", n = 34; "long-term non-withdrawers", n = 55). Also most of the non-withdrawers markedly reduced their benzodiazepine use. RESULTS: Within three weeks after initiating withdrawal, handgrip strength improved significantly (P ≤ 0.005) compared to baseline values. Among women, long-term withdrawers improved their handgrip strength both when compared to their baseline values (P = 0.001) or to non-withdrawers (P =0.004). In men, improvement of handgrip strength from baseline was not significantly better in withdrawers than in non-withdrawers. However, men did improve their handgrip strength values compared to baseline (P = 0.002). Compared to balance test results at baseline, withdrawers improved starting from the first week after withdrawal initiation. There was, however, only a borderline difference (P = 0.054) in balance improvement between the long-term withdrawers and long-term non-withdrawers. Of note, the non-withdrawers tended to improve their handgrip strength and balance compared to baseline values, in parallel with their reduced benzodiazepine use. CONCLUSIONS: Withdrawal from long-term use of benzodiazepines can rapidly improve muscle strength and balance. Our results encourage discontinuing benzodiazepine hypnotics, particularly in older women who are at a high risk of falling and sustaining fractures. TRIAL REGISTRATION: EU Clinical Trials Register: EudraCT2008000679530. Registered 31 October 2008.

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial.

AIM: We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. METHODS: A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. RESULTS: There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. CONCLUSIONS: Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo.

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

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.