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.
Persons with Alzheimer's disease (AD) are frequently hospitalized from infection-related causes. There are no previous studies investigating hospitalization associated with antibiotic initiation in persons with AD.
To investigate the frequency and risk of hospitalization associated with oral antibiotic initiation among community dwellers with and without AD.
We performed a retrospective register-based study utilizing register-based Medication Use and Alzheimer's disease (MEDALZ) cohort. It includes all community dwellers diagnosed with AD during 2005-2011 in Finland and their matched comparison persons without AD. Antibiotic use was initiated by 34,785 persons with and 36,428 without AD. Drug use data were collected from Prescription Register and comorbidities from Special Reimbursement and Hospital Care Registers. Infection diagnoses were collected from the Hospital Care Register. Factors associated with hospitalization were estimated utilizing logistic regression models.
Risk of hospitalization following antibiotic initiation was higher among antibiotic initiators with AD than without AD (adjusted odds ratio, aOR, 1.37, 95% Cl 1.28-1.46).Strongest association with hospitalization was found for oral glucocorticoid use, aOR 1.41 (1.25-1.59); epilepsy, aOR 1.33 (1.10-1.63); and active cancer, aOR 1.30 (1.14-1.49). Among initiators of cephalexin, pivmecillinam, amoxicillin/amoxicillin, and enzyme inhibitor and doxycycline, persons with AD were more frequently hospitalized than persons without AD. A quarter of hospitalized antibiotic initiators had infection diagnosis in their hospital care records.
Persons with AD initiating an antibiotic had a higher risk for hospitalization than antibiotic initiators without AD. Further research is needed to determine whether infection-related hospitalization could be reduced.
The study aimed to investigate the incidence of antidepressant use in persons with and without Alzheimer's disease (AD) from 9?years before to 4?years after AD diagnosis and to examine the incidence of different antidepressant groups.
We used register-based data from the Medication use and Alzheimer's disease cohort including all Finnish persons diagnosed with AD in 2005-2011 with their age-matched and gender-matched comparison persons without AD. In this study, 62,104 persons with AD and 62,104 comparison persons were included. Data on dispensed antidepressants during 1995-2012 were collected from the Prescription Register. A 1-year washout period was utilized to measure the rate of new antidepressant users every 6-month period starting from 9?years before and until 4?years after the AD diagnoses. The incidence rate between persons with and without AD was compared with Poisson regression.
The incidence of antidepressant use in persons with AD was higher during the whole study period compared with that in persons without AD. The incidence rate was highest at 6?months after AD diagnosis (incidence rate ratio?=?5.22, 95% confidence interval 4.77-5.72). Selective serotonin reuptake inhibitors were the most frequently initiated group (61.3% of initiations in persons with AD).
The objective of this study was to investigate whether incident opioid use is associated with an increased risk of hip fractures among community-dwelling persons with Alzheimer disease (AD) and to assess the association in terms of duration of use and opioid strength. Among community-dwelling persons with AD diagnosed in 2010 to 2011 (N = 23,100), a matched cohort study comparing incident opioid users (N = 4750) with opioid nonusers (N = 4750) was constructed. Matching was based on age, sex, and time since AD diagnosis at opioid initiation. Data on drug use and hip fractures were retrieved from nationwide registers. Incident opioid users were identified with a 1-year washout. Cox proportional hazard models compared the risk of hip fracture between opioid use and nonuse, and were weighted with inverse probability of treatment (IPT), based on a propensity score. Age-adjusted incidence rate of hip fractures was 3.47 (95% confidence interval [CI] 2.62-4.33) during opioid use and 1.94 (95% CI 1.65-2.22) during nonuse. Opioid use was associated with an increased risk of hip fracture (IPT-weighted hazard ratio [HR] 1.96, 95% CI 1.27-3.02). The risk was observed during the first 2 months of use (IPT-weighted HR 2.37, 1.04-5.41) and attenuated after that. The results suggest an increase in the risk of hip fracture by increasing opioid strength; weak opioids IPT-weighted HR 1.75 (0.91-3.35), buprenorphine IPT-weighted HR 2.10 (1.41-3.13), and strong opioids IPT-weighted HR 2.89 (1.32-6.32). Further research is needed to find out whether the risk of injurious falls is avoidable by slow titration of opioid doses in the beginning of treatment.
The aim of this study was to investigate the prevalence of benzodiazepine and related drug (BZDR) use, especially long-term use, and associated factors among community-dwelling individuals with and without Alzheimer's disease (AD). We utilized data from the MEDALZ-2005 cohort, which includes all community-dwelling individuals diagnosed with AD in Finland at the end of 2005 and matched comparison individuals without AD. Register-based data included prescription drug purchases, comorbidities, and hospital discharge diagnoses. In this study, 24,966 individuals with AD and 24,985 individuals without AD were included. During the 4-year follow-up, we found that 45% (N = 11,312) of individuals with AD and 38% (N = 9534) of individuals without AD used BZDRs. The prevalence of long-term (= 180 days) BZDR use was more common among individuals with AD (30%) than individuals without AD (26%). The median durations of the first long-term use periods of BZDRs were 1.5 and 2 years for individuals with and without AD, respectively. Factors associated with long-term BZDR use included female sex, AD, schizophrenia, bipolar disorder, depression, coronary artery disease, and asthma/chronic obstructive pulmonary disease. The high prevalence of long-term BZDR use among individuals with AD is especially a cause for concern because long-term use may further impair cognition and may be associated with serious adverse events.
Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease.
A matched cohort study was conducted by comparing new antidepressant users (n?=?10,910) with two matched nonusers (n?=?21,820) in the MEDALZ study cohort. The MEDALZ cohort includes all community-dwelling persons newly diagnosed with Alzheimer's disease between 2005 and 2011 in Finland. Incident antidepressant users were identified based on register-based dispensing data from the Prescription register with a 1-year washout period for antidepressant use. Nonusers were matched with users based on age, gender, and time since Alzheimer's disease diagnosis. The outcome events were defined as any head injuries and traumatic brain injuries based on diagnoses in Hospital Discharge and Causes of Death registers. Propensity score adjusted Cox proportional hazard models were utilized. Sensitivity analyses with case-crossover design were conducted. All registers are linkable with unique personal identification numbers assigned for each resident.
Antidepressant use was associated with an increased risk of head injuries (age-adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49-3.06) during use and 2.43 (95% CI 2.06-2.35) during nonuse, adjusted hazard ratio (HR) 1.35, 95% CI 1.20-1.52) and traumatic brain injuries (age-adjusted event rate per 100 person-years 1.33 (95% CI 1.13-1.53) during use and 1.10 (95% CI 1.00-1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06-1.50). The risk was highest during the first 30 days of use (HR 1.71, 95% CI 1.10-2.66 for head injuries; HR 2.06, 95% CI 1.12-3.82 for traumatic brain injuries) and remained at an elevated level for head injuries for over 2 years of use. In case-crossover analyses, antidepressant use was consistently associated with a higher risk of head injuries.
Antidepressant use was associated with an increased risk of the most severe outcomes, head and brain injuries, in persons with Alzheimer's disease. Antidepressant use should be carefully considered and the association confirmed in future studies.
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It is unknown whether cognitive status or diagnosed cognitive decline affects estrogen use.
We assessed how common systemic estrogen use was among community-dwellers with Alzheimer's disease (AD) and a matched comparison cohort without AD.
This study included an exposure-matched cohort of all Finnish community-dwelling women who received a clinically verified diagnosis of AD in 2005-2011 (N?=?46,116; index cases) and an equally sized matched comparison cohort without AD. Follow-up began on the matching date (date of the AD diagnosis of the index case). Data on systemic estrogen use were obtained from the prescription register. Use initiation and discontinuation were assessed.
Altogether 3.1% of women with AD and 4.3% of women without AD used estrogen during the follow-up period. Only?