The objective of this study was to investigate the prevalence of acetylcholinesterase inhibitor (AChEI) and memantine use, duration of treatment, concomitant use of these drugs, and factors associated with the discontinuation of AChEI therapy during 2006-2009. We utilized data from a nationwide sample of community-dwelling individuals with a clinically verified Alzheimer's disease diagnosed during the year 2005 (n=6858) as a part of the MEDALZ-2005 study. During the 4-year follow-up, 84% used AChEI and 47% used memantine. Altogether, 22% of the sample used both drugs concomitantly. The median duration of the first AChEI use period was 860 (interquartile range 295-1458) days and 1103 (interquartile range 489-1487) days for the total duration of AChEI use. Although 20% of the AChEI users discontinued the use during the first year, over half of them restarted later. The risk of discontinuation was higher for rivastigmine [hazard ratio 1.34 (confidence interval 1.22-1.48)] and galantamine users [hazard ratio 1.23 (confidence interval 1.15-1.37)] compared with donepezil users in the adjusted model. In conclusion, median time for AChEI use was over 3 years and every fifth Alzheimer's disease patient used AChEI and memantine concomitantly during the follow-up. The low rate of discontinuation is consistent with the Finnish Care Guideline but in contrast to the results reported from many other countries.
It is unknown if antidepressant treatment is associated with either increased or decreased risk of suicide.
To estimate the risk of suicide, attempted suicide, and overall mortality during antidepressant treatments in a real-life setting with high statistical power.
A cohort study in which all subjects without psychosis, hospitalized because of a suicide attempt from January 1, 1997, to December 31, 2003, in Finland, were followed up through a nationwide computerized database.
A total of 15 390 patients with a mean follow-up of 3.4 years.
The propensity score-adjusted relative risks (RRs) during monotherapy with the most frequently used antidepressants compared with no antidepressant treatment.
In the entire cohort, fluoxetine use was associated with the lowest risk (RR, 0.52; 95% confidence interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially lower mortality was observed during selective serotonin reuptake inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P
Comment In: Evid Based Ment Health. 2007 Aug;10(3):9017652572
To study whether antidepressant use is associated with an increased risk of hip fracture among community-dwelling persons with and without Alzheimer's disease (AD), and to compare the risk according to duration of use and between antidepressant groups.
Retrospective cohort study, including 50,491 persons with AD (mean age 80) and 100,982 comparison persons without AD from Finnish register-based MEDALZ cohort. Antidepressant use was compared with nonuse with Cox proportional hazard models. Incident users were identified with a one year washout period from Prescription register data. Main outcome was hospitalization due to hip fracture.
During antidepressant use, the age-adjusted rate of hip fractures per 100 person-years was 3.01 (95% CI 2.75-3.34) among persons with and 2.28 (1.94-2.61) among persons without AD. Antidepressant use was associated with an increased risk of hip fracture among persons with and without AD (adjusted HR 1.61, 95% CI 1.45-1.80 and 2.71, 2.35-3.14, respectively) compared with nonuse. The risk was most prominent in the beginning of use and was elevated even up to 4 years. The risk was increased with all of the most frequently used antidepressants.
Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (
Antipsychotic polypharmacy (APP) is not recommended in treatment of behavioral and psychological symptoms of dementia (BPSD). There is lack of studies concerning prevalence of APP among persons with dementia.
The objective of our study was to describe prevalence and risk factors associated with antipsychotic polypharmacy among antipsychotic users with Alzheimer's disease (AD).
Data from nationwide MEDALZ-2005 cohort including all community-dwelling persons diagnosed with AD in Finland was utilized. Register-based data included prescriptions, comorbidities, and hospital discharge diagnoses. Users of antipsychotics during 2006-2009 were included (n = 9,803). The risk of starting antipsychotic polypharmacy was evaluated with Cox proportional hazards model.
Prevalence of antipsychotic polypharmacy was 8% (n = 750) among antipsychotic users (n = 9,803). Quetiapine and risperidone was the most common combination of two antipsychotics followed by combination of quetiapine and haloperidol. Antipsychotic polypharmacy was associated with younger age (HR 1.35 [Confidence Interval, CI, 1.16-1.56]), male gender (HR 1.18 [CI 1.02-1.38]), and history of psychiatric disorder (HR 1.50 [CI 1.26-1.78]) in the adjusted model.
In conclusion, we found higher prevalence of APP than previously reported among older populations. This is concerning since effectiveness of APP has not been demonstrated and APP is not recommended in the treatment of BPSD. Clinicians should pay more attention to avoid APP and use of antipsychotics to other indications than BPSD among persons with AD.
The use of antipsychotic agents has been associated with increased pneumonia risk, but although people with dementia are particularly susceptible to pneumonia, only one small study has assessed the risk of pneumonia in relation to the use of antipsychotic agents among people with Alzheimer disease (AD).
We investigated whether the incident use of antipsychotic agents, or specific antipsychotic agents, are related to a higher risk of hospitalization or death due to pneumonia in the Medication and Alzheimer Disease (MEDALZ) cohort. The cohort includes all individuals with AD who received a clinically verified AD diagnosis in Finland in 2005 to 2011 (N = 60,584; incident pneumonia, n = 12,225). A matched comparison cohort without AD (N = 60,584; incident pneumonia, n = 6,195) was used to compare the magnitude of risk. Results were adjusted for a propensity score derived from comorbidities, concomitant medications, and sociodemographic characteristics. Sensitivity analyses with case-crossover design were conducted.
The use of antipsychotic agents was associated with a higher risk of pneumonia (adjusted hazard ratio [HR], 2.01; 95% CI, 1.90-2.13) in the AD cohort and a somewhat higher risk in the non-AD cohort (adjusted HR, 3.43; 95% CI, 2.99-3.93). Similar results were observed with case-crossover analyses (OR, 2.02; 95% CI, 1.75-2.34 in the AD cohort and OR, 2.59; 95% CI, 1.77-3.79 in the non-AD cohort). The three most commonly used antipsychotic agents (quetiapine, risperidone, haloperidol) had similar associations with pneumonia risk.
Regardless of applied study design, treatment duration, or the choice of drug, the use of antipsychotic agents was associated with a higher risk of pneumonia. With observational data, we cannot fully rule out a shared causality between pneumonia and the use of antipsychotic agents, but the risk to benefit balance should be considered when antipsychotic agents are prescribed.
The aim of the Medicine use and Alzheimer's disease (MEDALZ) study is to investigate the changes in medication and healthcare service use among persons with Alzheimer's disease (AD) and to evaluate the safety and effectiveness of medications in this group. This is important, because the number of persons with AD is rapidly growing and even though they are a particularly vulnerable patient group, the number of representative, large-scale studies with adequate follow-up time is limited.
MEDALZ contains all residents of Finland who received a clinically verified diagnosis of AD between 2005 and 2011 and were community-dwelling at the time of diagnosis (N=70 719). The diagnosis is based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCS-ADRDA) and Diagnostic and Statistical Manual Fourth Edition (DSM-IV) criteria for Alzheimer's disease. The cohort contains socioeconomic data (education, occupational status and taxable income, 1972-2012) and causes of death (2005-2012), data from the prescription register (1995-2012), the special reimbursement register (1972-2012) and the hospital discharge register (1972-2012). Future updates are planned.The average age was 80.1 years (range 34.5-104.6 years). The majority of cohort (65.2%) was women. Currently, the average length of follow-up after AD diagnosis is 3.1 years and altogether 26 045 (36.8%) persons have died during the follow-up.
Altogether 53% of the cohort had used psychotropic drugs within 1 year after AD diagnoses. The initiation rate of for example, benzodiazepines and related drugs and antidepressants began to increase already before AD diagnosis.
We are currently assessing if these, and other commonly used medications are related to adverse events such as death, hip fractures, head injuries and pneumonia.
Cites: Lancet. 2015 Nov 28;386(10009):2145-9126321261
Dementia, with Alzheimer's disease (AD) being the most common form, is a major hip fracture risk factor, but currently it is not known whether the same factors predict hip fracture among persons with and without dementia/AD. We compared the predictors of hip fracture and mortality after hip fracture in persons with and without AD.
An exposure-matched cohort of all community-dwellers of Finland who received a new clinically verified AD diagnosis in 2005-2011 and had no history of previous hip fracture (N = 67,072) and an age, sex, and region-matched cohort of persons without AD (N = 67,072). Associations between sociodemographic characteristics, comorbidities and medications and risk of hip fracture and mortality after hip fracture were assessed with Cox regression.
As expected, the incidence of hip fractures in 2005-2012 (2.19/100 person-years vs 0.90/100 person-years in the non-AD cohort), as well as mortality after hip fracture (29/100 person-years vs 23/100 person-years in the non-AD cohort) were higher in the AD cohort. This difference was evident regardless of the risk factors. Mental and behavioural disorders (adjusted hazard ratio; HR 95% confidence interval CI: 1.16, 1.09-1.24 and 1.71, 1.52-1.92 in the AD and non-AD-cohorts), antipsychotics (1.12, 1.04-1.20 and 1.56, 1.38-1.76 for AD and non-AD-cohorts) and antidepressants (1.06, 1.00-1.12 and 1.34 1.22-1.47 for AD and non-AD-cohorts) were related to higher, and estrogen/combination hormone therapy (0.87, 0.77-0.9 and 0.79, 0.64-0.98 for AD and non-AD-cohorts) to lower hip fracture risk in both cohorts. Stroke (1.42, 1.26-1.62), diabetes (1.13, 0.99-1.28), active cancer treatment (1.67, 1.22-2.30), proton pump inhibitors (1.14, 1.05-1.25), antiepileptics (1.27, 1.11-1.46) and opioids (1.10, 1.01-1.19) were associated with higher hip fracture risk in the non-AD cohort. Similarly, the associations between mortality risk factors (age, sex, several comorbidities and medications) were stronger in the non-AD cohort.
AD itself appears to be such a significant risk factor for hip fracture, and mortality after hip fracture, that it overrules or diminishes the effect of other risk factors. Thus, it is important to develop and implement preventive interventions that are suitable and effective in this population.
Given the high prevalence of psychotropic medication use in people with dementia and the potential for different prescribing practices in men and women, our study aimed to investigate sex differences in psychotropic medication use in older adults with Alzheimer's disease (AD) living in the US and Finland.
We used data collected between 2005 and 2011 as part of the National Alzheimer's Coordinating Center (NACC) in the US, and Medication use and Alzheimer's disease (MEDALZ) cohorts in Finland. We evaluated psychotropic medication use (antidepressant, antipsychotic, anxiolytic, sedative, or hypnotic) in participants aged 65 years or older. We employed multivariable logistic regression adjusted for demographics, co-morbidities, and other medications to estimate the magnitude of the association (adjusted odds ratio [aOR] with 95% confidence intervals [CIs]) according to sex.
We included 1099 NACC participants (502 [45.68%] men, 597 [54.32%] women), and 67,049 participants from the MEDALZ cohort (22,961 [34.24%] men, 44,088 [65.75%] women). Women were more likely than men to use psychotropic medications: US, 46.2% vs. 33.1%, p
Concomitant use of acetylcholine esterase inhibitors (AChEIs) and anticholinergic drugs, such as urinary antispasmodics (UA), is generally considered as inappropriate because of their opposite pharmacological actions. However, prevalence and the duration or factors associated with concomitant use have not been previously studied among community-dwelling persons with Alzheimer disease (AD). The aim of this study was to examine the prevalence and duration of concomitant use of AChEIs and UAs among community-dwelling persons with AD and factors associated with concomitant use. Register-based data of the MEDALZ-2005 Study included all community-dwelling persons with clinically diagnosed AD at the end of year 2005 in Finland. Persons using AChEI drugs during the 4-year follow-up (2006-2009) were included in the present study (n = 20,442). Among AChEI users, 1576 persons used UA during the follow-up. Prevalence of concomitant use of AChEIs and UAs was 7.3% (n = 1491) during the 4-year follow-up. The median duration of concomitant use was 236 days. Factors associated with concomitant use were age younger than 80 years (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.34), male sex (OR, 1.16; 95% CI, 1.04-1.30), Parkinson disease (OR, 1.98; 95% CI, 1.55-2.52), diabetes (OR, 1.25; 95% CI, 1.08-1.45), and prostatic cancer (OR, 1.54; 95% CI, 1.13-2.09). Despite their antagonizing action, concomitant use of AChEIs and UAs was quite common among Finnish community-dwelling persons with AD. In addition, duration of concomitant use was comparatively long. It is recommended to consider some other options than UAs to treat urinary incontinence among persons with AD.