Juha Puustinen

Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly.

AbstractObjective: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. Methods: A non-randomised clinical study of patients aged ≥65 years admitted to acute hospital wards during 1 month. 164 patients (mean age ± standard deviation [SD] 81.6 ± 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring ≥20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. Results: The mean ± SD duration of BZD/RD use was 7 ± 7 years (range 1–31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. Conclusions: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.

Effects of Potent Anticholinergics, Sedatives and Antipsychotics on Postoperative Mortality in Elderly Patients with Hip Fracture: A Retrospective, Population-Based Study

AbstractBackground: Concomitant use of several medications for somatic and mental disorders is common in elderly people and increases the risk of falls, with hip fracture being the most serious consequence. Objective: The objective of this study was to describe relationships between use of sedatives, antipsychotics or potent anticholinergics and postoperative mortality in patients with hip fractures. Methods: A retrospective analysis was conducted on population-based data collected during a 2-year period from 1999 to 2000 on 461 hip fracture surgery patients aged ≥65 years in Finland. Information on co-morbidities and intake of sedatives, antipsychotics and potent anticholinergics was obtained from the original patient records. Information on deaths was obtained from the official death statistics in Finland. Results: In men, use of potent anticholinergics was associated with excess age-adjusted mortality at 30 days, 3 months, 6 months and 3 years, but not in women at any timepoint. Use of potent anticholinergic drugs emerged as an independent predictor of excess mortality in men at 3 months and 3 years. Presence of cardiovascular disease and chronic lung disease were independent risk factors for excess mortality at 6 months and 3 years in men. In addition, chronic lung disease independently predicted excess mortality at 30 days. Conclusion: Use of potent anticholinergics should be evaluated critically after diseases.

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

BackgroundPrevious 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.MethodsWe 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.ResultsAfter 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.ConclusionsOf 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.

Psychotropic drugs and the risk of fractures in old age: a prospective population-based study

BackgroundThere is evidence that the use of any psychotropic and the concomitant use of two or more benzodiazepines are related to an increased risk of fractures in old age. However, also controversial results exist. The aim was to describe associations between the use of a psychotropic drug, or the concomitant use of two or more of these drugs and the risk of fractures in a population aged 65 years or over.MethodsThis study was a part of a prospective longitudinal population-based study carried out in the municipality of Lieto, South-Western Finland. The objective was to describe gender-specific associations between the use of one psychotropic drug [benzodiazepine (BZD), antipsychotic (AP) or antidepressant (AD)] or the concomitant use of two or more psychotropic drugs and the risk of fractures in a population 65 years or over. Subjects were participants in the first wave of the Lieto study in 1990-1991, and they were followed up until the end of 1996. Information about fractures confirmed with radiology reports in 1,177 subjects (482 men and 695 women) during the follow-up was collected from medical records. Two follow-up periods (three and six years) were used, and previously found risk factors of fractures were adjusted as confounding factors separately for men and women. The Poisson regression model was used in the analyses.ResultsThe concomitant use of two or more BZDs and the concomitant use of two or more APs were related to an increased risk of fractures during both follow-up periods after adjusting for confounding factors in men. No similar associations were found in women.ConclusionsThe concomitant use of several BZDs and that of several APs are associated with an increase in the risk of fractures in older men. Our findings show only risk relations. We cannot draw the conclusion that these drug combinations are causes of fractures.

Opioids, antiepileptic and anticholinergic drugs and the risk of fractures in patients 65 years of age and older: a prospective population-based study

BACKGROUND in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

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.

The Use of Chemical Restraints for Older Long-Term Hospital Patients: A Case Report from Finland

The purpose of this study was to describe the use and concomitant use of psychotropics and other drugs as chemical restraints in the aged in long-term hospital care. The study consisted of 154 patients (42 men, 112 women) hospitalized in five long-term care wards in Pori City Hospital, Finland. Three or more psychotropics were regularly given to 33% of the patients and regularly or irregularly to 53% of the patients. Two or more benzodiazepine derivatives or related drugs were regularly given to 24% of the patients and regularly or irregularly to 46% of the patients. The very poor cognitive and functional abilities of the patients, the common concomitant use of psychotropic drugs, the use of psychotropics to control the behavior of the patients, and the lack of documentation of the effects and side effects of the drugs give rise to the conclusion that psychotropics were used as chemical restraints in these long-term care wards.

Can Practical Nurses Identify Older Home Care Clients at Risk of Drug-Related Problems–Geriatricians’ Appraisal of Their Risk Screenings: A Pilot Study

Background: Home care (HC) clients are increasingly older, have many chronic diseases, and use multiple medicines and thus are at high risk for drug-related problems (DRPs). Objective: Establish the sensitivity of practical nurse (PN) administered DRP risk assessment tool (DRP-RAT) compared with geriatrician’s assessment of the medical record. Identify the clinically most significant DRPs needing action. Methods: Twenty-six PNs working in HC of Härkätie Health Center in Lieto, Finland, 46 HC clients (≥65 years), and a geriatrician participated in this pilot study. The geriatrician reviewed HC clients’ medications using 3 different methods. The reviews were based on the following: (1) the PN’s risk screening (ie, PN-completed DRP-RAT) and medication list, (2) health center’s medical records, and (3) methods 1 and 2 together. The main outcome was the number of “at-risk patients” (ie, the patient is at risk of clinically significant DRPs) by using each review method. Secondary outcomes were clinically most significant DRP-risk predicting factors identified by the geriatrician. Results: The geriatrician reviewed 45 clients’ medications using all 3 methods. Based on PN-completed DRP-RAT and medication list, 93% (42/45) of the clients were classified as “at-risk patients.” Two other review methods resulted in 45/45 (100%) “at-risk patients.” Symptoms suggestive of adverse drug reactions were the most significant risk predicting factors. Small sample size limits the generalizability of the results. Conclusions: The PN-completed DRP-RAT was able to provide clinically important timely patient information for clinical decision making. DRP-RAT could make it possible to more effectively involve PNs in medication risk management among older HC clients.

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.