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Antidementia drug use among community-dwelling individuals with Alzheimer's disease in Finland: a nationwide register-based study.

https://arctichealth.org/en/permalink/ahliterature260126
Source
Int Clin Psychopharmacol. 2014 Jul;29(4):216-23
Publication Type
Article
Date
Jul-2014
Author
Heidi Taipale
Antti Tanskanen
Marjaana Koponen
Anna-Maija Tolppanen
Jari Tiihonen
Sirpa Hartikainen
Source
Int Clin Psychopharmacol. 2014 Jul;29(4):216-23
Date
Jul-2014
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Alzheimer Disease - drug therapy
Cholinesterase Inhibitors - adverse effects - therapeutic use
Cohort Studies
Diagnostic and Statistical Manual of Mental Disorders
Drug Monitoring
Drug Prescriptions
Drug Therapy, Combination - adverse effects
Excitatory Amino Acid Antagonists - adverse effects - therapeutic use
Female
Finland
Follow-Up Studies
Galantamine - adverse effects - therapeutic use
Guideline Adherence
Humans
Indans - adverse effects - therapeutic use
Male
Memantine - adverse effects - therapeutic use
Nootropic Agents - adverse effects - therapeutic use
Phenylcarbamates - adverse effects - therapeutic use
Piperidines - adverse effects - therapeutic use
Practice Guidelines as Topic
Proportional Hazards Models
Registries
Abstract
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.
Notes
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PubMed ID
24608822 View in PubMed
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Antidepressant use and risk of hip fractures among community-dwelling persons with and without Alzheimer's disease.

https://arctichealth.org/en/permalink/ahliterature292637
Source
Int J Geriatr Psychiatry. 2017 12; 32(12):e107-e115
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
12-2017
Author
Sanna Torvinen-Kiiskinen
Anna-Maija Tolppanen
Marjaana Koponen
Antti Tanskanen
Jari Tiihonen
Sirpa Hartikainen
Heidi Taipale
Author Affiliation
Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.
Source
Int J Geriatr Psychiatry. 2017 12; 32(12):e107-e115
Date
12-2017
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Aged
Aged, 80 and over
Alzheimer Disease - complications
Antidepressive Agents - therapeutic use
Female
Finland - epidemiology
Hip Fractures - epidemiology
Hospitalization - statistics & numerical data
Humans
Male
Proportional Hazards Models
Retrospective Studies
Risk factors
Abstract
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.
Antidepressant use is associated with an increased risk of hip fracture among older persons. Copyright © 2017 John Wiley & Sons, Ltd.
Notes
CommentIn: Evid Based Nurs. 2017 Jul;20(3):94 PMID 28601807
PubMed ID
28055139 View in PubMed
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Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland.

https://arctichealth.org/en/permalink/ahliterature266764
Source
J Clin Psychopharmacol. 2014 Aug;34(4):435-40
Publication Type
Article
Date
Aug-2014
Author
Heidi Taipale
Marjaana Koponen
Antti Tanskanen
Anna-Maija Tolppanen
Jari Tiihonen
Sirpa Hartikainen
Source
J Clin Psychopharmacol. 2014 Aug;34(4):435-40
Date
Aug-2014
Language
English
Publication Type
Article
Keywords
Aged, 80 and over
Alzheimer Disease - drug therapy - epidemiology - psychology
Antipsychotic Agents - administration & dosage
Cohort Studies
Dose-Response Relationship, Drug
Female
Finland - epidemiology
Follow-Up Studies
Humans
Male
Residence Characteristics
Abstract
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 (
PubMed ID
24875073 View in PubMed
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Antipsychotic polypharmacy among a nationwide sample of community-dwelling persons with Alzheimer's disease.

https://arctichealth.org/en/permalink/ahliterature261391
Source
J Alzheimers Dis. 2014;41(4):1223-8
Publication Type
Article
Date
2014
Author
Heidi Taipale
Marjaana Koponen
Antti Tanskanen
Anna-Maija Tolppanen
Jari Tiihonen
Sirpa Hartikainen
Source
J Alzheimers Dis. 2014;41(4):1223-8
Date
2014
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Alzheimer Disease - drug therapy - epidemiology - psychology
Antipsychotic Agents - therapeutic use
Cohort Studies
Confidence Intervals
Databases, Factual - statistics & numerical data
Female
Finland
Humans
Male
Middle Aged
Polypharmacy
Residence Characteristics
Abstract
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.
PubMed ID
24787914 View in PubMed
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Antipsychotic Use and Risk of Hospitalization or Death Due to Pneumonia in Persons With and Those Without Alzheimer Disease.

https://arctichealth.org/en/permalink/ahliterature282670
Source
Chest. 2016 Dec;150(6):1233-1241
Publication Type
Article
Date
Dec-2016
Author
Anna-Maija Tolppanen
Marjaana Koponen
Antti Tanskanen
Piia Lavikainen
Reijo Sund
Jari Tiihonen
Sirpa Hartikainen
Heidi Taipale
Source
Chest. 2016 Dec;150(6):1233-1241
Date
Dec-2016
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Alzheimer Disease - complications - drug therapy
Antipsychotic Agents - adverse effects
Comorbidity
Cross-Over Studies
Female
Finland - epidemiology
Hospitalization - statistics & numerical data
Humans
Incidence
Male
Middle Aged
Pneumonia - mortality
Propensity Score
Risk factors
Socioeconomic Factors
Abstract
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.
PubMed ID
27298071 View in PubMed
Less detail

Cohort profile: the Finnish Medication and Alzheimer's disease (MEDALZ) study.

https://arctichealth.org/en/permalink/ahliterature287549
Source
BMJ Open. 2016 Jul 13;6(7):e012100
Publication Type
Article
Date
Jul-13-2016
Author
Anna-Maija Tolppanen
Heidi Taipale
Marjaana Koponen
Piia Lavikainen
Antti Tanskanen
Jari Tiihonen
Sirpa Hartikainen
Source
BMJ Open. 2016 Jul 13;6(7):e012100
Date
Jul-13-2016
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Alzheimer Disease - complications - diagnosis - drug therapy
Antidepressive Agents - adverse effects - therapeutic use
Benzodiazepines - adverse effects - therapeutic use
Cohort Studies
Diagnostic and Statistical Manual of Mental Disorders
Drug Evaluation
Drug Monitoring
Female
Finland
Humans
Male
Middle Aged
Patient Acceptance of Health Care
Psychotropic Drugs - adverse effects - therapeutic use
Abstract
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.
Notes
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PubMed ID
27412109 View in PubMed
Less detail

Drug use in persons with and without Alzheimer's disease aged 90 years or more.

https://arctichealth.org/en/permalink/ahliterature287349
Source
Age Ageing. 2016 Nov;45(6):900-904
Publication Type
Article
Date
Nov-2016
Author
Heidi Taipale
Marjaana Koponen
Antti Tanskanen
Anna-Maija Tolppanen
Jari Tiihonen
Sirpa Hartikainen
Source
Age Ageing. 2016 Nov;45(6):900-904
Date
Nov-2016
Language
English
Publication Type
Article
Keywords
Age Factors
Aged, 80 and over
Alzheimer Disease - diagnosis - drug therapy - epidemiology - psychology
Antidepressive Agents - therapeutic use
Antipsychotic Agents - therapeutic use
Bone Density Conservation Agents - therapeutic use
Chi-Square Distribution
Drug Prescriptions
Female
Finland - epidemiology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Logistic Models
Male
Odds Ratio
Polypharmacy
Practice Patterns, Physicians' - trends
Prevalence
Registries
Risk factors
Time Factors
Abstract
increasing number of persons reach very high age but few studies have investigated their drug use patterns.
to compare drug use among persons with Alzheimer's disease (AD) aged =90 years to persons without AD with similar age and to younger persons with AD.
register-based data were from the MEDALZ cohort including all community-dwelling persons diagnosed with AD 2005-11 in Finland. They were identified from Special Reimbursement register. One comparison person without AD was matched with age-, gender- and region of residence. Persons with AD were divided to those aged =90 years (N = 3,319) and
PubMed ID
27609205 View in PubMed
Less detail

Duration of new antidepressant use and factors associated with discontinuation among community-dwelling persons with Alzheimer's disease.

https://arctichealth.org/en/permalink/ahliterature300475
Source
Eur J Clin Pharmacol. 2019 Mar; 75(3):417-425
Publication Type
Journal Article
Date
Mar-2019
Author
Reetta Kettunen
Heidi Taipale
Anna-Maija Tolppanen
Antti Tanskanen
Jari Tiihonen
Sirpa Hartikainen
Marjaana Koponen
Author Affiliation
School of Pharmacy, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.
Source
Eur J Clin Pharmacol. 2019 Mar; 75(3):417-425
Date
Mar-2019
Language
English
Publication Type
Journal Article
Keywords
Age Factors
Aged
Aged, 80 and over
Alzheimer Disease - drug therapy
Antidepressive Agents - administration & dosage - therapeutic use
Antipsychotic Agents - administration & dosage - therapeutic use
Cohort Studies
Female
Finland
Humans
Independent living
Male
Proportional Hazards Models
Registries
Sex Factors
Time Factors
Abstract
To study how long antidepressants initiated after diagnoses of Alzheimer's disease (AD) were used and factors associated with discontinuation of use among persons with Alzheimer's disease (AD). In addition, differences in duration of use between the antidepressants groups were compared.
Register-based Medication use and Alzheimer's disease (MEDALZ) cohort included 70,718 community-dwelling people with AD who were diagnosed during the years 2005-2011. For this study, the new antidepressant users were included after 1-year washout period (N?=?16,501; 68.6% females, mean age 80.9). The duration of antidepressant use was modeled with the PRE2DUP method. Factors associated with treatment discontinuation were assessed with Cox proportional hazard models and included age, gender, comorbid conditions and concomitant medications.
Median duration of the new antidepressant use period was 309 days (IQR 93-830). For selective serotonin reuptake inhibitor (SSRI) use, the median duration was 331 days (IQR 101-829), for mirtazapine 202 days (IQR 52-635), and for serotonin and norepinephrine reuptake inhibitors (SNRIs) 134 days (IQR 37-522). After 1-year follow-up, 40.8% had discontinued antidepressant use, 54.6% after 2 years and 64.1% after 3 years. Factors associated with treatment discontinuation were age over 85, male gender, diabetes, and use of memantine, opioids, and antiepileptics whereas benzodiazepines and related drugs and antipsychotic use were inversely associated with discontinuation.
Antidepressants are used for long-term among people with AD. Need and indication for antidepressant use should be assessed regularly as evidence on their efficacy for behavioral and psychological symptoms of dementia is limited.
PubMed ID
30413841 View in PubMed
Less detail

From prescription drug purchases to drug use periods – a second generation method (PRE2DUP).

https://arctichealth.org/en/permalink/ahliterature271333
Source
BMC Med Inform Decis Mak. 2015;15:21
Publication Type
Article
Date
2015
Author
Antti Tanskanen
Heidi Taipale
Marjaana Koponen
Anna-Maija Tolppanen
Sirpa Hartikainen
Riitta Ahonen
Jari Tiihonen
Source
BMC Med Inform Decis Mak. 2015;15:21
Date
2015
Language
English
Publication Type
Article
Keywords
Drug Prescriptions - statistics & numerical data
Drug Utilization - statistics & numerical data
Finland
Humans
Models, Theoretical
Prescription Drugs
Registries - statistics & numerical data
Time Factors
Abstract
Databases of prescription drug purchases are now widely used in pharmacoepidemiologic studies. Several methods have been used to generate drug use periods from drug purchases to investigate various aspects; e.g., to study associations between exposure and outcome. Typically, such methods have been fairly simplistic, with fixed assumptions of drug use pattern and or dose (for example, the assumed usage of 1 tablet per day). This paper describes a novel PRE2DUP method that constructs drug use periods from purchase histories, and verified by a validation based on an expert evaluation of the drug use periods generated by the method.
The PRE2DUP method is a novel approach based on mathematical modelling of personal drug purchasing behaviors. The method uses a decision procedure that includes each person's purchase history for each ATC code, processed in a chronological order. The method constructs exposure time periods and estimates the dose used during the period by considering the purchased amount in Defined Daily Doses (DDDs), which is recorded in the prescription register database. This method takes account of stockpiling of drugs, personal purchasing pattern; i.e., regularity of the purchases, and periods of hospital or nursing home care where drug use is not recorded in the prescription register. The method can be applied to a variety of drug classes with different doses and use patterns by controlling restriction parameters for each ATC class, or even each drug package. In the presented example, the PRE2DUP method was applied to a register-based MEDALZ-2005 study cohort. All drug purchases (3,793,085) recorded in the Finnish prescription register between 2002 and 2009 for persons with Alzheimer's disease (28,093) were included.
Results of the expert-opinion based validation indicate that PRE2DUP method creates drug use periods with a relatively high correctness. Drugs with varying patterns of use and drugs used on a short-term basis only require more precise parameters.
PRE2DUP method gives highly accurate drug use periods for most drug classes, especially those meant for long-term use.
Notes
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PubMed ID
25890003 View in PubMed
Less detail

High prevalence of psychotropic drug use among persons with and without Alzheimer's disease in Finnish nationwide cohort.

https://arctichealth.org/en/permalink/ahliterature266724
Source
Eur Neuropsychopharmacol. 2014 Nov;24(11):1729-37
Publication Type
Article
Date
Nov-2014
Author
Heidi Taipale
Marjaana Koponen
Antti Tanskanen
Anna-Maija Tolppanen
Jari Tiihonen
Sirpa Hartikainen
Source
Eur Neuropsychopharmacol. 2014 Nov;24(11):1729-37
Date
Nov-2014
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Alzheimer Disease - drug therapy - epidemiology
Case-Control Studies
Cohort Studies
Drug Utilization - statistics & numerical data - trends
Female
Finland - epidemiology
Humans
Male
Mental Disorders - drug therapy - epidemiology
Middle Aged
Prevalence
Psychotropic Drugs - therapeutic use
Registries
Abstract
Psychotropic drugs are used for treatment of behavioral and psychological symptoms of dementia (BPSD) although they are associated with serious adverse drug events. Objective of our study was to investigate prevalence of psychotropic drug use one year after diagnoses of Alzheimer's disease (AD), to compare prevalence to persons without AD and to assess changes in prevalence over time. Data from the MEDALZ (Medication use and Alzheimer's disease) cohort was utilized in the study including all 69,080 community-dwelling persons with new diagnosis of AD during years 2005-2011 in Finland. Four age-, gender- and region of residence-matched persons without AD were identified for each case. Register-based data included prescription drug purchases and comorbidities from Special Reimbursement Register. Annual prevalence of psychotropic drug use one year after diagnosis was determined for each person. Psychotropic drugs were used by 53% of persons with AD compared with 33% of persons without AD during one year after diagnoses. Persons with AD were six times more likely to use antipsychotics and three times more likely to use antidepressants whereas benzodiazepine and related drug (BZDR) use was comparable between persons with and without AD. According to year of AD diagnoses during 2005-2011, antipsychotic use increased from 18% to 20% (p
PubMed ID
25453487 View in PubMed
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