CNS Medications as Predictors of Precipitous Cognitive Decline in the Cognitively Disabled Aged: A Longitudinal Population-Based Study

Background/Aims: Psychotropics and antiepileptics (AE) are medications commonly used among the aged with cognitive decline or dementia, although they may precipitate further cognitive decline. Our aim was to analyze the relationships between the use of (i) psychotropics (i.e. benzodiazepines or related drugs, BZD, antipsychotics, AP, or antidepressants, AD), opioids (Op), anticholinergics (ACh) or AEs or the concomitant use of two of these drugs, and (ii) the risk of precipitous cognitive decline in an older (≧65 years) cognitively disabled population. Methods: A longitudinal population-based study of general aged community-dwelling patients was executed in two phases (1990–1991 and 1998–1999) in Lieto, Finland. Fifty-two individuals cognitively disabled (MMSE score 0–23) at the 1990–1991 baseline form this study’s sample. Cognitive abilities were assessed in each phase with the Mini-Mental State Examination (MMSE) and medication utilization data were collected in both phases. The mean follow-up time was 7.6 years. Multivariate models were used to analyze the change in MMSE total score between medication users and non-users. Results: BZD or any psychotropic use was associated with greater cognitive decline in elders aged ≧75 years compared to non-users (change in MMSE sum score: –8.6 ± 7.0 vs. –3.3 ± 5.6 and –5.9 ± 7.0 vs. –2.7 ± 6.4, respectively). A greater decline was also associated specifically with the concomitant use of BZD and AP (–16 vs. –1.4 ± 7.8); as were BZD and any drug with CNS effects (–9.6 ± 9.9 vs. –1.3 ± 7.2) compared to non-users. The concomitant use of BZD and AD (–10.7 ± 4.7 vs. –3.2 ± 5.6) or ACh (–15.0 ± 8.5 vs. –3.3 ± 5.6) or any drug with CNS effects (–13.3 ± 6.5 vs. –3.3 ± 5.6) was associated with cognitive decline in patients ≧75 years compared to non-users of any drug with CNS effects. Conclusion: The use of a BZD or any psychotropic medication may be an independent risk factor for cognitive decline in the cognitively disabled aged, and patients co-prescribed psychotropic medications had greater cognitive decline. Studies with larger sample sizes and studies on possible pathophysiologic mechanisms are needed

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.Peer reviewe

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

Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study

<p>Abstract</p> <p>Background</p> <p>Previous studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (≥ 65 yrs) population that is cognitively intact at baseline.</p> <p>Methods</p> <p>We conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance.</p> <p>Results</p> <p>After adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men.</p> <p>Conclusions</p> <p>Of all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects.</p

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.Peer reviewe