Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Residents of Long-Term Care Facilities.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Effect of severity of depression on augmentation of antidepressant medication in young adults with depression.

BACKGROUND: Antipsychotics (AP) have been used to augment antidepressant (AD) medication in treatment-resistant depression. In this study we examined factors (including severity of depression and initial antidepressant) affecting AP augmentation, as well as which APs were initiated as augmentation in young adults. METHODS: Data were extracted from Finnish nationwide registers. Of persons aged 18-29 years diagnosed with a depression during 2004-2017 we focused on incident AD users (who initiated AD 6 months before and after the diagnosis) whose severity level of depression was recorded (N = 21,966). AP augmentation was studied during 1 year after diagnosis of depression. Persons diagnosed with severe depression with psychotic features (n = 1486) were excluded from main analyses and analyzed separately. RESULTS: Overall, 8.4% of new antidepressant users initiated AP augmentation. Risk of augmentation increased with severity of depression as 3.9%, 5.8%, and 14.0% of persons with mild, moderate, and severe depression, respectively, initiated augmentation. Male sex, comorbid anxiety and personality disorders, substance abuse and selfharm/suicide attempt were positively associated with augmentation. Compared to citalopram, use of tricyclic antidepressant, paroxetine and venlafaxine were associated with increased risk of augmentation, while use of bupropion was associated with a decreased risk. Quetiapine and risperidone were the most common APs used in augmentation. Among persons with severe depression with psychotic features, use of sertraline was associated with AP augmentation, whereas use of fluoxetine decreased risk of augmentation. CONCLUSIONS: Use of APs as augmentation of AD therapy was common in severe depression. Comorbidities had only a small effect to augmentation, but selection of initial AD was more closely associated to risk of augmentation. Interestingly, use of bupropion decreased risk of augmentation, which warrants further studies, as well as the decrease in risk of augmentation when fluoxetine in case of psychotic depression was used.

Diagnostic groups of hospital stays and outpatient visits during 10 years before Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a major determinant of healthcare costs and increase in the healthcare service use occur already before the AD diagnosis. However, little is known how the different diagnosis categories contribute to this increase in healthcare use. We investigated how the hospitalizations and specialized healthcare outpatient visits from different diagnosis categories, based on the International Classification of Diseases (ICD-10) chapters, contribute to increased specialized healthcare service use during ten-year period preceding AD diagnosis. METHODS: A register-based nationwide cohort of 42,934 community-dwelling persons who received clinically verified AD diagnosis in between 2008 and 2011 in Finland and 1:1 age, sex and hospital district- matched comparison cohort were included. Hospitalizations and specialized healthcare visits were categorized by the main diagnosis, according to the ICD-10 chapters. AD and dementia were separated to their own category. The number of persons with visits and stays was calculated for every 6 months, irrespective of the frequency of visits/stays individual had during that time window. Furthermore, the relative distribution of the diagnosis categories was computed. RESULTS: AD cohort was more likely to have visits and stays during the 10-year period (OR 1.19, 95% CI 1.17-1.21). The number of persons with visits and stays peaked in AD cohort from 1.5 years before the diagnosis when the differences in relative distribution of different diagnosis categories also became evident. The largest differences were observed for visits/stays with cognitive disorders, symptoms of unspecified diseases and psychiatric disorders diagnoses, and those with missing diagnosis codes in the last time window before AD diagnosis. CONCLUSIONS AND IMPLICATIONS: Increased healthcare service use before AD diagnosis does not seem to arise from differences in specific diagnosis categories of ICD-10 such as diseases of the circulatory system, but from the higher frequency of visits and stays among persons with AD across diagnosis categories. Based on the relative distribution of diagnosis categories, the steep increase in healthcare service use just before and during the diagnostic process is likely due to prodromal symptoms and visits related to cognition.

Incidence of cataract surgeries in relation to diagnosis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) causes also visual dysfunction including decreased visual acuity, even already at the prodromal phase of disease. Still, it has been suggested that persons with PD may be less likely to be referred for cataract surgery, although early management increases the chances for successful cataract surgery. METHODS: Data from nationwide register-based Finnish Study on Parkinson's Disease (N=22189) was used. This study included 17546 persons with PD diagnosed in 1996-2015 and 114817 comparison persons who were at least 45 years old. Comparison persons were matched for age (+/-1 year, sex and hospital district on the date of PD diagnosis (index date). Incidence of cataract surgeries was investigated from ten years before to ten years after the index date. Information on cataract surgeries and comorbidities were extracted from several nationwide healthcare registers. RESULTS: The incidence rate of cataract surgeries was 20.4/1000 and 18.7/1000 person-years (PY) for persons with or without PD, respectively. Before PD diagnosis, rate of surgeries was higher in persons with PD (incidence rate 16.5 vs 13.7 /1000PY, IRR, 95%CI 1.21, 1.16-1.26). After PD diagnosis there was no difference in the incidence rate. Persons who had undergone cataract surgery were older and had more eye diseases and other comorbidities compared to those without surgery. CONCLUSIONS: Diagnosis of PD does not decrease the incidence of cataract surgeries. Conversely, the incidence may be increased prior to PD diagnosis, probably due to other eye diseases and prodromal symptoms of PD.

Incidence of cataract surgeries in people with and without Alzheimer's disease.

PURPOSE: To investigate the incidence of cataract surgeries in relation to Alzheimer's disease (AD) diagnosis and to compare it with that in people without AD. METHODS: The MEDALZ-study includes community-dwelling Finnish persons who received clinically verified AD diagnoses (n = 70718) during 2005-2011 and a matched comparison cohort without AD (n = 70718). The cataract surgeries were identified from the Care Register for Healthcare (1996-2015) using NOMESCO surgical procedure codes CJE (10,15,20,25,99), CJF (00,10,20,30,40,45,50,55,99) and CJG (00,05,10,15,20,25,99). The incidence rates for surgeries per 100 person-years were calculated from 10 years before to 3 years after the index date (date of AD diagnosis from the Special Reimbursement Register). RESULTS: 25 763 cataract procedures were performed on persons with AD and 26 254 on persons without AD during the follow-up. The incidence of surgery increased similarly in both groups before the index date of AD diagnosis, and the rate of surgery was similar in people with and without AD (3.5 and 3.3/100 person-years, respectively). The incidence diminished steeply in the AD group already one year after the index date, whereas the slow increase continued in the non-AD group. After the index date, the rates were 3.7 and 4.7/100 person-years in people with and without AD. CONCLUSION: The diminishing surgery rate very soon after AD diagnosis is concerning. The stigma of AD diagnosis may lead to fewer referrals to surgery, although these patients are expected to benefit from surgery.

Changes in the use of diabetes drugs among community-dwelling people with Alzheimer's disease.

BACKGROUND: Type 2 diabetes is common in persons with Alzheimer's disease (AD). Management of diabetes in persons with AD is challenging due to changing goals of care and susceptibility to adverse drug events including hypoglycemia. The aim of this study was to investigate the prevalence of diabetes drug use from 5 years before to 5 years after the time of AD diagnosis among persons with and without AD. METHODS: This was a nationwide register-based study of persons with and without AD and diabetes in Finland. We analyzed data from the Medication Use and Alzheimer's disease (MEDALZ) study that included 70,718 community-dwelling people diagnosed with AD from 2005 to 2011. The study population included 8418 persons with AD and 6666 matched persons without AD who were diagnosed with diabetes 5 years before AD diagnosis (index date). We defined the prevalence of diabetes drug use in three-month evaluation periods from 5 years before until 5 years after the index date. RESULTS: Nearly all people with diabetes (94% in both cohorts) used one or more diabetes drugs on the index date. The most prevalent drug metformin was used by 60.9% of people with AD and 59.1% of people without AD. The next most prevalent drugs were sulfonylureas and insulin. The prevalence of diabetes drug use was similar in people with and without AD but began to decline 1 year after AD diagnosis in the AD cohort compared to non-AD cohort. CONCLUSIONS: The decline in diabetes drug use after AD diagnosis may be attributed to clinicians and patients seeking to avoid serious adverse drug events including hypoglycemia. In addition, the findings may reflect personalized glycemic control and unintentional weight loss in persons with AD reducing the need for diabetes drugs.

Switches and early discontinuations of antidepressant medication in young adults with depression.

BACKGROUND: Receiving treatment for depression is increasingly common among young adults. Antidepressants (AD) are important in depression treatment and modification of medication is common. We examined switches and discontinuations of ADs among young Finnish adults aged 18-29 years. METHODS: All persons diagnosed with depression in inpatient or specialized outpatient care or having received sickness absence or disability pension due to depression at age of 18-29 years during 2004-17 were included (N = 110761). Among them, we focused on incident AD users (N = 52855, 47.7%) who were identified with a 6 month washout before AD initiation. The follow-up was 2 years. RESULTS: The majority (76.3%) initiated with selective serotonin reuptake inhibitors (SSRIs). The initial AD was switched in 17.4% of cases. Switching was most common when treatment was initiated with tricyclic antidepressants (TCA) or polytherapy, and least common when initiated with SSRIs or serotonin-noradrenaline reuptake inhibitors. Factors associated with switch included initiation with polytherapy, TCA or mirtazapine, and use of benzodiazepines or Z-drugs at baseline. During the first 3 months, 27.6% discontinued AD use, and only 14.1% used AD for 2 years. Factors associated with discontinuation included substance abuse, ADHD, previous suicide attempt and initiation with mirtazapine. SSRIs had the longest time to discontinuation (median 144 days, IQR 64-302). LIMITATIONS: Our data sources lack those treated in primary care only, without receiving a sick leave of ≥2 weeks. In addition, we do not have data on severity of depression, social factors or psychotherapy. CONCLUSIONS: Special emphasis should be paid to persons with increased risk of discontinuation, including those with previous self-harm/suicide attempt or substance abuse.

Asthma and Chronic Obstructive Pulmonary Disease as a Comorbidity and Association with the Choice of Antidementia Medication Among Persons with Alzheimer's Disease.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common comorbidities in persons with Alzheimer's disease (AD). However, pharmacotherapy of these diseases may have opposite mechanisms of action; anticholinergics in asthma/COPD and acetylcholinesterase inhibitors (AChEI) in AD. OBJECTIVE: To investigate whether existing asthma/COPD affects the choice of AD medication, and the survival of the patients with AD. METHODS: In this retrospective cohort study, data from the MEDALZ-study, which includes all community-dwelling persons with AD during 2005-2011 in Finland (n = 70718) was utilized. Persons with asthma/COPD (N = 7211) were defined as having a special reimbursement for asthma/COPD, or long-term use (≥250 days) of inhaled anticholinergics, inhaled corticosteroids, or leukotriene antagonists during the year before AD diagnosis. We compared persons with and without asthma/COPD regarding the choice of the initial antidementia medication (AChEI versus memantine) with logistic regression and mortality with Cox regression model during the follow-up (up to end of 2015). RESULTS: Memantine was favored over AChEIs as first-line treatment to AD in persons with asthma/COPD compared to those without asthma/COPD (odds ratio 1.23, 95% confidence interval (CI) 1.15-1.31). Memantine was also more commonly used among those who used multiple asthma/COPD medications (7.9% of memantine initiators used ≥3 asthma/COPD medications compared with 5.5% of those who initiated with AChEI). Mortality was higher in persons with asthma/COPD compared to those without asthma/COPD (adjusted hazard ratio 1.10, 95% CI 1.07-1.13). CONCLUSION: More frequent use of memantine instead of AChEI may result from an attempt to prevent possible worsening of asthma/COPD by AChEIs. Vulnerable persons with both AD and asthma/COPD need individually assessed pharmacotherapy for their medical conditions.

Antiepileptic Drug Use Is Associated with an Increased Risk of Pneumonia Among Community-Dwelling Persons with Alzheimer's Disease-Matched Cohort Study.

BACKGROUND: Antiepileptic drugs (AEDs) have sedative properties which may lead to an increased risk of pneumonia. OBJECTIVES: To investigate whether incident AED use is associated with an increased risk of pneumonia among community-dwelling persons with Alzheimer's disease (AD). In addition, we determined the risk according to duration of AED use and specific AEDs. METHODS: Persons with AD were identified from the MEDALZ dataset which includes all community-dwelling persons who received a clinically verified diagnosis of AD during 2005-2011 in Finland (N=70,718). New AED users were identified with one-year washout period. A matched cohort (1 : 1, N=5,769, matching criteria age, gender, and time since AD diagnoses) of nonusers was formed. Data from nationwide registers included dispensed medications which were modelled with PRE2DUP method, hospitalizations, and causes of death. The association between AED use and hospital admission or death due to pneumonia was analyzed with Cox proportional hazard models. RESULTS: AED use was associated with an increased risk of pneumonia (adjusted HR 1.92, 95% CI 1.63-2.26; incidence rate per 100 person-years 12.58, 95% CI 12.49-12.66 during AED use and 6.41, 95% CI 6.37-6.45 during nonuse). The highest risk was observed during the first month of use (aHR 3.59, 95% CI 2.29-5.61) and the risk remained elevated until two years of use. Of specific drug substances, phenytoin, carbamazepine, valproic acid, and pregabalin were associated with an increased risk. CONCLUSION: Antiepileptic drug use may increase the risk of pneumonia which is concerning as persons with AD have elevated risk of pneumonia.

Antipsychotic Use and the Risk of Initiating Medication for Benign Prostate Hyperplasia in Persons With Alzheimer Disease: A Matched Cohort Study.

BACKGROUND: Antipsychotics (APs) are known to exacerbate symptoms of benign prostate hyperplasia (BPH) and may even cause urinary retention. The anticholinergic effects of APs and their dopamine D2- and α-receptor blockade may lead to voiding dysfunction of BPH patients. The objective of our study was to investigate whether the use of APs is associated with an increased risk of initiating medication for BPH in men with Alzheimer disease (AD). METHODS: Data from the nationwide MEDALZ (MEDication use and ALZheimer's disease) cohort, including all community-dwelling persons diagnosed with AD in Finland, were utilized. Register-based data included medication dispensing, comorbidities, and hospital discharge diagnoses. Men who initiated APs (n = 4579) were 1:1 matched with men who did not initiate APs (n = 4579), according to time since AD diagnoses and age. The risk of starting BPH medication was investigated with Cox regression. RESULTS: Among AP users, BPH medication was initiated to 345 persons (7.5%). Antipsychotic use was not associated with risk of initiating BPH medication (comorbidity-adjusted hazard ratio, 0.92; 95% confidence interval, 0.74-1.15) compared with no use of APs. In addition, no risk was found when AP drug substances were analyzed separately. CONCLUSIONS: Use of APs did not increase the risk of initiating medication for BPH in men with AD.

Anticholinergic burden and dry mouth among Finnish, community-dwelling older adults.

OBJECTIVE: The aim was to study whether the anticholinergic burden of drugs is related to xerostomia and salivary secretion among community-dwelling elderly people. BACKGROUND: Anticholinergic drugs have been shown to be a risk factor for dry mouth, but little is known about the effects of cumulative exposure to anticholinergic drugs measured by anticholinergic burden on salivary secretion or xerostomia. METHODS: The study population consisted of 152 community-dwelling, dentate, non-smoking, older people from the Oral Health GeMS study. The data were collected by interviews and clinical examinations. Anticholinergic burden was determined using the Anticholinergic Drug Scale (ADS). A Poisson regression model with robust error variance was used to estimate relative risks (RR) with 95% confidence intervals (CI 95%). RESULTS: Participants with a high-anticholinergic burden (ADS ≥ 3) were more likely to have xerostomia (RR: 3.17; CI: 1.44-6.96), low-unstimulated salivary flow (<0.1 mL/min; RR: 2.31, CI: 1.22-4.43) and low-stimulated salivary flow (<1.0 mL/min; RR: 1.50, CI: 0.80-2.81) compared to reference group (ADS 0). In participants with a moderate anticholinergic burden (ADS 1-2), all the risk estimates for xerostomia, unstimulated and stimulated salivary secretion varied between 0.55 and 3.13. Additional adjustment for the total number of drugs, antihypertensives and sedative load caused only slight attenuation of the risk estimates. CONCLUSION: A high-anticholinergic burden was associated with low-unstimulated salivary secretion and xerostomia.

Is Alzheimer's Disease Associated with Previous Opioid Use?

Objective: We investigated whether opioid use, duration of use, and cumulative dose are associated with an increased risk of Alzheimer's disease (AD). Methods: A Finnish nationwide nested case-control study, MEDALZ, included 70,718 individuals with AD and up to four age-, sex-, and region of residence-matched comparison individuals. The cohort included all Finnish persons with a clinically verified AD diagnosis during 2005 to 2011; the mean age was 80 years (SD = 7 years), and 65% were women. Register-based data on opioid purchases (excluding codeine) were modeled into drug use periods using the PRE2DUP method. Cumulative opioid doses were transformed to total standardized doses (TSDs). We utilized a three-year time window between exposure (opioid use) and outcome (AD) to avoid reverse causality. Analyses were adjusted for comorbid conditions and drug use. Results: Opioid use was not associated with an increased risk of AD (adjusted odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.98-1.03). Neither longer duration of use (cumulative use for >365 days: adjusted OR = 1.02, 95% CI = 0.96-1.08) nor high cumulative doses (>90 TSDs: adjusted OR = 1.02, 95% CI = 0.98-1.07) of opioids was associated with risk of AD. Conclusions: Although opioid use was not associated with an increased risk of AD, further studies should be performed to assess the safety of long-term opioid use in terms of other cognitive effects.

Anticholinergic Exposure and Risk of Pneumonia in Persons with Alzheimer's Disease: A Nested Case-Control Study.

BACKGROUND: Risk of pneumonia is increased in persons with Alzheimer's disease (AD). In some studies, anticholinergic drugs (AC) have been associated with an increased pneumonia risk. OBJECTIVE: We analyzed the risk of pneumonia associated with ACs in persons with AD. METHODS: We performed a nested case-control study using register-based data from a Finnish nationwide MEDALZ cohort including all community-dwelling persons diagnosed with AD during 2005-2011. Cases were identified based on pneumonia diagnoses (n = 12,442) from hospital discharge and causes of death registers. Up to two controls without pneumonia were matched based on time since AD diagnoses, age, and gender for each case; AC use was measured using Anticholinergic Drug Scale. RESULTS: Use of AC was associated with an increased risk of pneumonia (adjusted odds ratio (OR) 1.36, 95% confidence interval (CI) 1.29-1.43). However, there was no increased pneumonia risk in persons using level 3 ACs. Incident use was associated with higher risk of pneumonia (OR 2.68, 95% CI 2.15-3.34) than prevalent use (OR 1.48, 95% CI 1.40-1.57). Among persons using cholinesterase inhibitors (AChEIs), risk of pneumonia was increased in persons using also ACs (OR 1.53, 95% CI 1.41-1.66). CONCLUSION: ACs were associated with an increased risk of pneumonia in persons with AD, especially at the time of initiation of these drugs. AC use was associated with increased pneumonia risk also in persons using AChEIs. This risk should be carefully considered when treating AD patients.

The effect of comprehensive geriatric assessment on anticholinergic exposure assessed by four ranked anticholinergic lists.

BACKGROUND: Older people often use multiple drugs, and some of them have anticholinergic activity. Anticholinergic drugs may cause adverse reactions, and therefore their use should be limited. To identify anticholinergic load, several ranked lists with different drugs and scoring systems have been developed and used widely in research. We investigated, if a comprehensive geriatric assessment (CGA) decreased the anticholinergic drug score in a 4-year period. We used four different anticholinergic ranked lists to determine the anticholinergic score and to describe how the results differ depending on the list used. METHODS: We analyzed data from population-based intervention study, in which a random sample of 1000 persons aged ≥75 years were randomized to either an intervention group or a control group. Those in the intervention group underwent CGA including medication assessment annually between 2004 and 2007. Current medication use was assessed annually. The anticholinergic load was calculated by using four ranked lists of anticholinergic drugs (Boustani's, Carnahan's, Chew's and Rudolph's) for each person and for each year. RESULTS: CGA had no statistically significant effect on anticholinergic exposure during the 4-year follow-up, but improvements towards more appropriate medication use were observed especially in the intervention group. However, age, gender and functional comorbidity index were associated to higher anticholinergic exposure, depending on the list used. CONCLUSIONS: Repeated CGAs may result as more appropriate anticholinergic medication use. The selection of the list may affect the results and therefore the selection of the list is important.

Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer's disease.

INTRODUCTION: Persons with Alzheimer's disease are at an increased risk of pneumonia, but the comparative risks during specific antidementia treatments are not known. We compared the risk of pneumonia in the use of donepezil, rivastigmine (oral, transdermal), galantamine and memantine. PATIENTS AND METHODS: We used data from a nationwide cohort of community-dwelling individuals diagnosed with Alzheimer's disease during 2005-2011 in Finland, who initiated monotherapy with acetylcholinesterase inhibitor or memantine (n = 65,481). The risk of hospitalization or death due to pneumonia was investigated with Cox proportional hazard models. RESULTS: The risk of pneumonia was higher in persons using rivastigmine patch (n = 9709) (adjusted hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04-1.27) and memantine (n = 11,024) (HR 1.59, 95% CI 1.48-1.71) compared with donepezil users (n = 26,416) whereas oral rivastigmine (n = 7384) (HR 1.08, 95% CI 0.98-1.19) and galantamine (n = 10,948) (HR 0.91, 95% CI 0.83-1.00) were not associated with an increased risk. These results did not change when adjusting for comorbid conditions, use of psychotropic drugs or with inverse probability of treatment weighting. DISCUSSION: The increased risk of pneumonia in this fragile group of aged persons should be taken into account. Memantine is associated with the highest risk in the comparison of antidementia drugs. KEY Message Pneumonia risk is increased in persons with Alzheimer's disease who use memantine or rivastigmine patches.

Central Anticholinergic Adverse Effects and Their Measurement.

Drugs with anticholinergic properties are widely used. However, they may evoke a variety of adverse reactions (such as dry mouth and constipation, but also drowsiness and confusion), and therefore unnecessary use of drugs with anticholinergic properties should be avoided. In particular, older people are particularly vulnerable to the central anticholinergic effects of drugs. However, monitoring of drug-induced anticholinergic effects and drug concentrations in serum is challenging. In addition to the 'pure' anticholinergics such as atropine and oxybutynin, several other drugs whose principal mode of action is not anticholinergic, possess anticholinergic properties, thus increasing the risk of anticholinergic adverse effects. In this paper, we focus on the central anticholinergic effects of drugs, and on the usefulness of the serum anticholinergic assay (SAA) in the prediction of anticholinergic effects. Results on the anticholinergic effects of drugs on cognition are mixed. This may be because of differences in the populations as well as in the drugs used. In addition, the clinical conditions of the patients may affect the results. The SAA has been used in an attempt to measure anticholinergic burden. However, the results are variable and the SAA levels do not necessarily reflect the medication used by the patient. Therefore, its usefulness in determining anticholinergic adverse reactions is questionable.

Anticholinergic drug use, serum anticholinergic activity, and adverse drug events among older people: a population-based study.

BACKGROUND: The serum anticholinergic activity (SAA) assay has been used to quantify patients' anticholinergic load. In addition, several ranked lists of anticholinergic drugs have been developed to assess anticholinergic drug burden. OBJECTIVE: This study investigated whether SAA assay results and scores from three ranked lists of anticholinergic drugs (Carnahan's Anticholinergic Drug Scale, Rudolph's Anticholinergic Risk Scale, and Chew's list) are associated with anticholinergic adverse drug events (ADEs) in older people. METHODS: We analyzed data from participants in the population-based Geriatric Multidisciplinary Good Care of the Elderly Study in Kuopio, Finland (n = 621). Demographic, diagnostic, and drug use data were collected during standardized interviews and verified from medical records. Vision, functional capacity, cognition, and mood were assessed using validated techniques. The SAA was measured from blood samples. RESULTS: The SAA was not associated with anticholinergic ADEs. Anticholinergic drug burden computed using each of the three lists was inversely associated with short-distance vision (p < 0.01), activities of daily living (p < 0.05), and instrumental activities of daily living (p < 0.05) in persons with and without dementia. Furthermore, poorer Mini Mental State Examination and poorer Geriatric Depression Scale scores were associated with the anticholinergic drug burden in persons without dementia (p < 0.05-p < 0.001). The association between anticholinergic drug burden and ADEs was strongest when using the lists developed by Carnahan and Chew. CONCLUSIONS: Scores obtained from ranked lists of anticholinergic drugs were associated with clinically significant anticholinergic ADEs but the SAA was not. This finding supports the usefulness of these lists to help identify patients at risk of anticholinergic ADEs in clinical practice.

Comprehensive geriatric assessment decreases prevalence of orthostatic hypotension in older persons.

BACKGROUND: Orthostatic hypotension (OH) is associated with significant morbidity and mortality among older people. We have studied whether its prevalence can be reduced by a Comprehensive Geriatric Assessment (CGA). STUDY DESIGN AND SETTING: 1000 randomly-selected persons aged ≥75 years were divided into intervention (n = 500) and control groups (n = 500). We focused on those subjects in whom an orthostatic blood pressure test had been performed at least once during the study period (2004-2007) (n = 365 and 332 for intervention and control groups, respectively). A CGA, including evaluation of the adequacy of the medication, was performed annually in the intervention group but not in the control group. We conducted Markov models to study change in the OH profiles and the effect of CGA on it. Competing risk of mortality was modeled as an absorbing state to avoid attrition bias. RESULTS: Over 3 years, the prevalence of OH decreased (35.0% → 28.0%) in the intervention group, whereas its prevalence increased in the control group (32.8% → 40.8%). By Markov models it was shown that CGA had a statistically significant effect on recovering from OH. In addition, CGA was shown to protect from developing OH. CONCLUSIONS: Repeated CGA performed annually can reduce the prevalence of OH.