Anticholinergic Levels Research Articles

Anticholinergic Burden of Geriatric Ward Inpatients.

Background and Objectives: Anticholinergic drug use in the pharmacotherapy of elderly persons is common despite the increased risk of side effects. We examined the prevalence of anticholinergic drug use and total anticholinergic drug burden among patients admitted to an acute care geriatric ward in Poland. Materials and Methods: Cross-sectional study of 329 subjects hospitalized at the geriatric ward. Patient condition was assessed with a comprehensive geriatric assessment. The Anticholinergic Cognitive Burden (ACB) scale was used to estimate the total anticholinergic load. Results: Mean patient age was 79.61 ± 6.82 years. 40.73% of them were burdened with at least one anticholinergic drug. The clinically significant anticholinergic burden was observed in 13.98% of subjects. Patients with dementia, risk of falls, and severe disability had significantly higher total ACB scores compared to other groups. The receiver operating characteristics (ROC) curve revealed that the total ACB score ≥ 1 was significantly associated with dementia and the risk of falls. Total ACB score ≥ 2 was significantly associated with severe disability. Conclusions: Patients admitted to an acute care geriatric ward had an anticholinergic cognitive burden score comparable to other patient populations. We found associations at both low and elevated levels of anticholinergic burden with dementia and risk of falls. At elevated anticholinergic burden levels, we found associations with severe disability. Despite recommendations against the use of anticholinergics in older adults these medications are still commonly prescribed. Further study is necessary to define the characteristics of anticholinergic medication most closely associated with negative outcomes in elderly populations.

Measuring cumulative anticholinergic medicines burden in older Australian women

ABSTRACT
 ObjectivesAnticholinergic medicines burden is common, can have negative impacts, and is problematic to identify. Many medicines used by older women have anticholinergic effects. Importantly for older women, where multimorbidity and use of multiple medicines is common, even when anticholinergic effect of an individual medicine is small, the anticholinergic effects of multiple medicines may be additive, constituting cumulative anticholinergic burden. This study describes medicines contributing to and predictors of anticholinergic burden among community-dwelling older Australian women.
 ApproachRetrospective longitudinal analysis of data from the Australian Longitudinal Study on Women’s Health linked to Pharmaceutical Benefits Scheme medicines data from 1 January 2008 to 30 December 2010; for 3694 women born in 1921–1926.Anticholinergic medicines were assigned anticholinergic potency levels 0 to 3, according to the Anticholinergic Drug Scale. Anticholinergic Drug Scale ratings for all medicines used by each woman were summed across each six months to give an Anticholinergic Drug Scale score. Commonly used medicines were identified for women with high ADS scores (defined as 75th percentile of scores). Predictors of high ADS scores were analysed using generalised estimating equations. 
 ResultsDuring 2008-2010, 1126 (59.9%) of women used at least one anticholinergic medicine. Median Anticholinergic Drug Scale score was 4. Most anticholinergic medicines used by women who had a high anticholinergic burden (Anticholinergic Drug Scale score > 9) had a low anticholinergic potency (Anticholinergic Drug Scale level 1). Increasing age, cardiovascular disease, and number of other medicines used were predictive of a higher anticholinergic burden.
 ConclusionHigh anticholinergic medicines burden in this group was driven by use of multiple lower anticholinergic potency medicines rather than use of higher potency medicines. While we might expect that doctors would readily identify anticholinergic burden risk for those using high potency medicines, they may be less likely to identify this risk for users of multiple low potency anticholinergic medicines. The paper will also discuss how GPs view these findings, and how to translate them into the prescribing setting.

Potentially inappropriate medications (PIMs) and anticholinergic levels in the elderly: A population based study in a French region

Prescriptions of PIMs and anticholinergic drugs lead to adverse events and hospitalizations in the elderly. The objective of this study was to determine the prevalence of PIMs and prescriptions with a high anticholinergic effect in a French region. All prescriptions dispensed at community pharmacies in patients aged 75 and older between January 1 and March 31, 2012 were extracted from French Health Insurance information System – Nord-Pas-de-Calais Region for patients affiliated to the Social Security. Prescription of PIMs was defined according to the Laroche list. The anticholinergic score for each prescription was calculated using the Anticholinergic Drug Scale (ADS). 65.6% (n=207,979) of people aged over 75 years, living in the Nord-Pas-de-Calais Region were included, of which 4.5% (n=9284) living in nursing homes. Patients received an average of 8.3 drugs over the 3-month study period. In 32.6% (n=67,863) of patients, at least one PMI was prescribed. According to the ADS, 10.0% (n=20,978) of patients in the general population and 24.0% (n=2231) of patients living in nursing homes was exposed to a prescription with a high or very high anticholinergic score (ADS≥3). Hydroxyzine prescribed in 51.4% (n=10,792) of them ranked first among drugs most often reported. In conclusion, PMIs and anticholinergic drugs were commonly prescribed in elderly living in the Nord-Pas-de-Calais Region. Improving the quality of prescriptions in the elderly appears necessary.

Cognitive Risks of Anticholinergics in the Elderly

Many drugs commonly prescribed to the elderly have anticholinergic properties. Due to the current clinical use of drugs with mild-to-modest anticholinergic activity, the clinical manifestations of anticholinergic toxicity are likely to be nonspecific (e.g., cognitive impairment) and reflect the effects of cumulative anticholinergic burden. Age-associated physiological and pharmacokinetic changes increase anticholinergic drug effects in later life. Those with cognitive impairment and neurodegeneration are particularly susceptible to anticholinergic toxicity. Recent findings suggest that chronic anticholinergic burden may hasten or contribute to a neurodegenerative process. APOE ε4 carrier status may be a genetic risk factor for vulnerability to negative anticholinergic effects. There is no clinically available laboratory test to assess anticholinergic levels. Clinicians need to be cognizant of anticholinergic risks in later life. The use of clinical scales (e.g., Anticholinergic Drug Scale) and consensus guidelines (e.g., Revised Beers Criteria) may be helpful.

Significant correlation between plasma and CSF anticholinergic activity in presurgical patients

Previous studies have suggested a possible link between cognitive impairment and anticholinergic burden as reflected by high serum anticholinergic activity (SAA). Thus, we hypothesized a close relationship between anticholinergic activity in cerebral spinal fluid (CSF) and blood. However, it has never been convincingly demonstrated that peripheral anticholinergic activity correlates with central anticholinergic levels in presurgical patients. Therefore, anticholinergic activity was measured in blood and CSF from 15 patients with admission scheduled for urological surgery to compare peripheral and central anticholinergic level. Blood and CSF probes were taken after routine premedication and before spinal anesthesia. Anticholinergic activity was determined by competitive radioreceptor binding assay for muscarinergic receptors. Correlation analysis was conducted for peripheral and central anticholinergic levels. The mean anticholinergic levels were 2.4 ± 1.7 in the patients’ blood and 5.9 ± 2.1 pmol/mL of atropine equivalents in CSF. Interestingly, the anticholinergic activity in CSF was about 2.5-fold higher than in patients’ blood. A significant linear correlation was detected between blood and CSF levels. Therefore we conclude that SAA levels adequately reflect central anticholinergic activity. When patients receiving or not receiving anticholinergic medication were compared, anticholinergic activity tended to increase in blood and CSF after receiving anticholinergic medication ≥4 weeks ( p > 0.05).

Cognitive, Behavioral, and Physiological Changes in Alzheimer Disease Patients as a Function of Incontinence Medications

Objective Authors evaluated the cognitive, neurophysiologic, and behavioral effects of incontinence medications in patients with Alzheimer disease (AD). Methods Nine patients were evaluated, both on and off incontinence medication, for cognitive status, neuropsychiatric status, activities of daily living, and serum anticholinergic level. Caregivers were interviewed to evaluate behavioral status and caregiver burden. Results Patients showed better performance on specific measures of cognition and behavior when not taking medication for incontinence. A significant, inverse correlation was found between mental status and anticholinergic level. Conclusion Although the sample size was small, the findings suggest that, in patients with AD, incontinence medications with anticholinergic properties may have detrimental effects on mental status and behavior.

Cognitive, Behavioral, and Physiological Changes in Alzheimer Disease Patients as a Function of Incontinence Medications

Authors evaluated the cognitive, neurophysiologic, and behavioral effects of incontinence medications in patients with Alzheimer disease (AD). Nine patients were evaluated, both on and off incontinence medication, for cognitive status, neuropsychiatric status, activities of daily living, and serum anticholinergic level. Caregivers were interviewed to evaluate behavioral status and caregiver burden. Patients showed better performance on specific measures of cognition and behavior when not taking medication for incontinence. A significant, inverse correlation was found between mental status and anticholinergic level. Although the sample size was small, the findings suggest that, in patients with AD, incontinence medications with anticholinergic properties may have detrimental effects on mental status and behavior.

Anticholinergic delirium: Assessing the role of anticholinergic burden in the elderly

Intoxication due to anticholinergic burden, exposure to multiple medications with anticholinergic effects, is one of the most common and potentially preventable causes of delirium in the elderly. This paper reviews the basic and clinical literature supporting the ubiquitous nature of this syndrome. Clinical studies in which serum and plasma anticholinergic levels have been measured and correlated with presence and severity of confusional states and delirium are highlighted. They provide the best available support for the anticholinergic hypothesis of delirium. Special emphasis is placed on studies of anticholinergics in patients with Alzheimer disease (AD). Because of the pre-existing cholinergic “lesion” in AD, they may be particularly vulnerable to the effects of anticholinergics. Two recent studies support this, suggesting a deleterious effect on clinical course of AD and possibly on its pathophysiology.

Anticholinergicity and cognitive processing in chronic schizophrenia

Patients with chronic schizophrenia suffer from alterations in cholinergic functioning due to several factors, including the disease diathesis and pharmacologic treatments. Acetylcholine–cognition relationships are well explored in normals but are unclear in schizophrenia. Prior work indicated serum anticholinergicity does not cause global cognitive impairment in this group ( Tracy et al., 1998a), raising the possibility that anticholinergicity normalizes an abnormal hyperactive cholinergic state. Serum anticholinergic levels were determined in 38 chronic schizophrenia patients using an established radioreceptor assay method. Six cognitive functions associated with cholinergic tone in normals were tested. The potential role of autonomic arousal and cigarette smoking were also assessed as both have been linked to cholinergic functioning. Regression analyses showed measures of inhibitory executive control and effortful memory accounted for a greater proportion of the variance in the anticholinergicity measure compared to the other variables. The data demonstrate a relationship between high anticholinergicity and worse performance on two types of attention-resource demanding cognitive processes and do not support the notion that reduced cholinergic tone normalizes a hyperactive cortical acetylcholine substrate. Relevant neuroanatomic structures and implications for models of cognitive deficits in schizophrenia are discussed.

Therapeutic Effects of Imipramine Are Counteracted by Its Metabolite, Desipramine, in Patients With Generalized Anxiety Disorder

Imipramine has been shown to reduce anxiety in patients with generalized anxiety disorder (GAD). However, some properties of imipramine may diminish or counteract its anxiolytic effects. The authors previously found that the greater the reduction in cardiac vagal control after 6 weeks of imipramine treatment, the smaller the improvement in anxiety-related symptoms. The purpose of this study was to determine whether the authors' previous findings were replicable and to gather information on the plasma levels of imipramine, desipramine (the major metabolite of imipramine), and anticholinergic levels. Fourteen patients with GAD were administered imipramine for 6 weeks. Their scores from self-administered and investigator-administered rating scales were obtained before and after the treatment, and the changes in these scores were contrasted with the changes in cardiac vagal tone, along with the absolute plasma levels of imipramine, desipramine, and anticholinergic activity at the end of week 6. The authors observed a greater improvement in symptoms of anxiety in those who showed the smallest decreases in cardiac vagal tone and in those who showed the smallest increases in desipramine and anticholinergic plasma levels. Moreover, strong relationships were observed between desipramine and anticholinergic levels. These results demonstrate that imipramine not only has therapeutic effects, but it may also have properties that result in physiologic states that counteract its therapeutic effects. Future research should investigate the direct anticholinergic effects of desipramine and determine whether there is a parallel between the anticholinergic effects and the clinical outcome of other pharmacologic treatments, including antidepressants with predominantly norepinephrine or serotonin reuptake inhibitory properties.

Anticholinergic Differences Among Patients Receiving Standard Clinical Doses of Olanzapine or Clozapine

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.

Serum anticholinergic activity levels and delirium in the elderly.

This article will briefly review the clinical studies focusing on measurement of serum levels of anticholinergic activity in delirious states. Three experimental approaches have been taken. First, to identify medications currently prescribed that have subtle anticholinergic effects. The current "list" includes 48 commonly prescribed medications. Second, to associate serum anticholinergic activity with delirium in various clinical states including postcardiotomy delirium, postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing home patients. Third, to intervene in patients with elevated anticholinergic activity by reducing known anticholinergics and correlating this reduction with clinical measures of cognition and delirium. Our most recent data investigate the impact of anticholinergics on demented patients. Prevalence of delirium was significantly higher in patients receiving larger numbers of anticholinergics.

Relation of Serum Anticholinergicity to Cognitive Status in Schizophrenia Patients Taking Clozapine or Risperidone

A potential beneficial outcome of treatment with certain of the atypical neuroleptics is the reduced risk of cognitive impairment, stemming from purported low affinity for cholinergic receptors. In vitro experiments have shown that clozapine is highly anticholinergic and risperidone is minimally so. In vivo tests of the anticholinergic burden imposed by these medications and its potential cognitive consequences are needed. This study examines anticholinergic burden in schizophrenia patients taking clozapine and risperidone and tests whether this burden is associated with cognitive deficits. Serum anticholinergic levels were determined in a sample of 22 chronic schizophrenia patients using the radioreceptor assay method of Tune and Coyle (1980). Fifteen patients received clozapine; 7 received risperidone. Mean +/- SD age of the sample, comprising 12 men and 10 women (68% white), was 44.7 +/- 8.4 years. Mean +/- SD age at onset of schizophrenia illness was 23.5 +/- 7.4 years. Two anticholinergic assays based on blood samples collected 1 week apart were available on each patient. Data indicated that clozapine patients had significantly (p < .001) higher anticholinergic levels at both collection points, and levels for both drugs remained stable over time. The clozapine and risperidone patients had essentially equivalent scores on the cognitive measure. These data suggest that anticholinergicity distinguishes clozapine and risperidone in vivo but that this effect is not associated with differences in global cognitive functioning. Results suggest that clozapine, despite producing moderately high in vivo serum anticholinergic levels, still holds clinical advantage over standard neuroleptics in terms of cognitive side effects. Reasons for this lowered risk of cognitive impairment are discussed.

P-13-13 - Ratio of neuroleptic to anticholinergic level and extrapyramidal symptoms induced by nemonapride

Treatment-emergent tardive dyskinesia (TD) can be a serious side effect of antipsychotic treatment. Atypical antipsychotics are associated with a lower risk for TD than are conventional agents. A long-acting atypical antipsychotic, with more stable blood levels and lower peak blood levels than an oral formulation, may provide differential benefit regarding side effects, including movement disorders. This analysis assessed TD by defined research criteria in patients receiving long-acting, injectable risperidone.Clinically stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week, open-label trial of long-acting, injectable risperidone. TD was studied by defined research criteria (Schooler and Kane, 1982, American Psychiatric Association, 2000). The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale (ESRS).ESRS dyskinesia data were available for 662 patients. Five of 530 subjects without dyskinesia at baseline (0.94%) met the predefined criteria for emergent persistent TD during therapy. Based on either exposure to study medication or Kaplan–Meier analysis, the 1-year rate was 1.19%. Among the 132 subjects with dyskinesia at baseline, the mean score on the ESRS physician's exam for dyskinesia improved significantly at endpoint (− 2.77; P < 0.0001), regardless of anticholinergic drug use. (P = 0.243 for patients with versus without anticholinergic drug use.)In this open-label study, treatment with long-acting risperidone was associated with a low rate of emergent persistent TD. Significant improvement in existing dyskinesias was noted. The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics.

Increased anticholinergic levels, memory and judgement

AbstractClinicians who have contact with patients taking medications which produce cholinergic blockade may need to consider possible links between increased anticholinergic levels and problems in judgement. Although it appears that there has as yet been no direct experimental test of the impact of anticholinergic agents on the judgement of normals or psychiatric patients, a review is offered of two types of basic cognitive findings which strongly suggest that the risk of such a link should figure in clinical cost—benefit analysis. It is then argued that, in the absence of definitive findings, several clinical considerations suggest that the clinician should consider the possible impact of anticholinergics on judgement in his or her practice.

Anticholinergic serum levels and cognitive performance

Integrity of central cholinergic neurotransmission is essential for adequate cognitive functioning. Many psychotherapeutic medications have anticholinergic side-effects. In order to determine the impact of circulating anticholinergic activity on cognitive performance, 28 geropsychiatric inpatients underwent cognitive testing at different levels of anticholinergic serum activity. In 10 subjects with a diagnosis of probable Alzheimer's disease, significant deterioration of selected cognitive functions was observed at anticholinergic serum levels that caused no dysfunction in the 18 non-demented subjects. The data suggest that non-demented elderly patients with psychiatric problems tolerate psychotropic pharmacotherapy without significant negative impact on their cognitive competency. By contrast, patients with Alzheimer's disease are at risk of additional impairment. The introduction of anticholinergic serum activity as a monitoring technique for safe psychopharmacotherapy in geriatric patients is discussed.

Effects of anticholinergic medication on memory in schizophrenia

Verbal memory and reaction time of ten schizophrenia patients were compared at two different serum anticholinergic levels. Verbal recall was worse at higher drug levels, while reaction time tended to be improved by anticholinergic treatment. Implications for studies of memory in schizophrenia are considered.

Serum haloperidol and anticholinergic levels in drug-induced parkinsonism

Serum haloperidol and anticholinergic levels in drug-induced parkinsonism

The Relationship of Symptomatology and Medication to Electrodermal Activity in Schizophrenia

An electrodermal assessment procedure using mild innocuous tones, task-relevant tones, and loud white noise was administered to a sample of schizophrenic patients (n = 77). The present study investigated the relationship of schizophrenic symptomatology and anticholinergic level of neuroleptic medication to electrodermal variables. Each patient was evaluated for positive (florid) and negative (defect) symptoms. The neuroleptics that patients received were rated according to their anticholinergic effect. No significant differences in symptomatology were observed between electrodermal responders and nonresponders; however, nonresponders showed a nonsignificant tendency to have more positive and negative symptoms than responders. Both negative symptoms and anticholinergic levels were significant predictors of lower tonic levels of skin conductance. Patients receiving high anticholinergic neuroleptics showed significantly reduced measures of electrodermal responsivity and tonic levels. Thus, both symptomatology and type of neuroleptic are related to electrodermal measures, with the anticholinergic effect of neuroleptic medication being more pronounced.

Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients.

Low-dose scopolamine, given as presurgery medication, resulted in low levels of serum anticholinergic activity and caused measurable cognitive impairment in 18 psychiatrically healthy elderly patients. The degree of impairment was directly related to serum anticholinergic activity levels and, in the small subgroup of patients scheduled for spinal anesthesia, to CSF anticholinergic activity. Two of the mental status tests used, the Rey Auditory-Verbal Learning Test and the Saskatoon Delirium Checklist, were sensitive enough to detect these mild drug-induced changes, while two other tests, the Mini-Mental State and the Symbol Digit Modalities Test, were not.