Biomedical subjects

Benoit H Mulsant

Publications and source records attributed to Benoit H Mulsant.

At least 55 records · Page 3Linked to original sources

PubMed2005

Somatic symptoms in late-life anxiety: treatment issues.

Understanding and addressing somatic symptoms are complex in older adults, who have more comorbid medical illnesses. This article describes a systematic review of the literature on somatic symptoms in older patients with anxiety disorders. Additionally, the hypothesis was tested that somatic symptoms would respond to selective serotonin reuptake inhibitor treatment in 30 anxious patients aged 60 years and older who participated in a 32-week trial of citalopram. The literature review showed few original data articles about somatic symptoms in older patients with anxiety disorders. These articles suggest that such a relationship is common and that treatment of anxiety, or anxious depression, is associated with a reduction in somatic symptoms. In the analysis, citalopram treatment was associated with a significant decrease in several somatic symptoms from pretreatment baseline. It is concluded that somatic symptoms in older adults with anxiety disorders or anxious depression often improve with successful antidepressant treatment. However, additional treatment and integrated approaches are likely to be necessary for many such individuals.

Age of Onset↗

PubMed2005

Predictors of remission after electroconvulsive therapy in unipolar major depression.

CONTEXT: Electroconvulsive therapy (ECT) is the most effective biological treatment for major depression. However, there is little agreement about clinically useful predictors of acute ECT outcomes. OBJECTIVE: To assess whether age, sex, burden of comorbid physical illness, age at onset, history of recurrence, episode duration, chronic depression or comorbid dysthymia, melancholic features, episode severity, and medication resistance are predictors of remission after an acute course of ECT. DESIGN: We performed an analysis using data gathered prospectively in 328 patients with unipolar major depression (according to Research Diagnostic Criteria) treated with ECT. The study was conducted from 1993 through 1999. Patients had a pretreatment score of 21 or higher on the 24-item Hamilton Rating Scale for Depression (HAM-D). Treatment history was assessed using the Antidepressant Treatment History Form. Remission was defined as a 24-item HAM-D score of 10 or less and a 60% or more relative reduction of the HAM-D score. RESULTS: On univariate logistic regression, statistically significant predictors of nonremission were chronic depression/dysthymia, medication resistance, longer episode duration, and younger age. On backward elimination logistic regression, only medication resistance (OR = 1.67, 95% CI = 1.05 to 2.67) and chronic depression/ dysthymia (OR = 1.84, 95% CI = 1.06 to 3.21) were statistically significant predictors of nonremission. CONCLUSIONS: In patients with major depression, lower rates of remission after acute ECT are associated with medication resistance and chronicity, but not with age or burden of physical illness.

Age of Onset↗

PubMed2004

Estimating treatment effects from longitudinal clinical trial data with missing values: comparative analyses using different methods.

The selection of a method for estimating treatment effects in an intent-to-treat analysis from clinical trial data with missing values often depends on the field of practice. The last observation carried forward (LOCF) analysis assumes that the responses do not change after dropout. Such an assumption is often unrealistic. Analysis with completers only requires that missing values occur completely at random (MCAR). Ignorable maximum likelihood (IML) and multiple imputation (MI) methods require that data are missing at random (MAR). We applied these four methods to a randomized clinical trial comparing anti-depressant effects in an elderly depressed group of patients using a mixed model to describe the course of the treatment effects. Results from an explanatory approach showed a significant difference between the treatments using LOCF and IML methods. Statistical tests indicate violation of the MCAR assumption favoring the flexible IML and MI methods. IML and MI methods were repeated under the pragmatic approach, using data collected after termination of protocol treatment and compared with previously reported results using piecewise splines and rescue (treatment adjustment) pragmatic analysis. No significant treatment differences were found. We conclude that attention to the missing-data mechanism should be an integral part in analysis of clinical trial data.

Aged↗

PubMed2004

Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial.

CONTEXT: Suicide rates are highest in late life; the majority of older adults who die by suicide have seen a primary care physician in preceding months. Depression is the strongest risk factor for late-life suicide and for suicide's precursor, suicidal ideation. OBJECTIVE: To determine the effect of a primary care intervention on suicidal ideation and depression in older patients. DESIGN AND SETTING: Randomized controlled trial known as PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) with patient recruitment from 20 primary care practices in New York City, Philadelphia, and Pittsburgh regions, May 1999 through August 2001. PARTICIPANTS: Two-stage, age-stratified (60-74, > or =75 years) depression screening of randomly sampled patients; enrollment included patients who screened positive and a random sample of screened negative patients. This analysis included patients with a depression diagnosis (N = 598). INTERVENTION: Treatment guidelines tailored for the elderly with care management compared with usual care. MAIN OUTCOME MEASURES: Assessment of suicidal ideation and depression severity at baseline, 4 months, 8 months, and 12 months. RESULTS: Rates of suicidal ideation declined faster (P =.01) in intervention patients compared with usual care patients; at 4 months, in the intervention group, raw rates of suicidal ideation declined 12.9% points (29.4% to 16.5%) compared with 3.0% points (20.1% to 17.1% in usual care [P =.01]). Among patients reporting suicidal ideation, resolution of ideation was faster among intervention patients (P =.03); differences peaked at 8 months (70.7% vs 43.9% resolution; P =.005). Intervention patients had a more favorable course of depression in both degree and speed of symptom reduction; group difference peaked at 4 months. The effects on depression were not significant among patients with minor depression unless suicidal ideation was present. CONCLUSIONS: Evidence of the intervention's effectiveness in community-based primary care with a heterogeneous sample of depressed patients introduces new challenges related to its sustainability and dissemination. The intervention's effectiveness in reducing suicidal ideation, regardless of depression severity, reinforces its role as a prevention strategy to reduce risk factors for suicide in late life.

Aged↗

PubMed2004

Paroxetine-induced hyponatremia in older adults: a 12-week prospective study.

BACKGROUND: Older depressed patients are at high risk for development of hyponatremia after initiation of the selective serotonin reuptake inhibitor paroxetine, despite clinical monitoring and preventive management. The purposes of this study were to determine the incidence and etiology of paroxetine-induced hyponatremia in older patients and to identify patient characteristics that may account for variability in susceptibility to this adverse event. METHODS: This prospective, longitudinal study was conducted in a university-based ambulatory psychiatric research clinic from August 1999 through September 2001. Patients included 75 men and women aged 63 through 90 years (mean +/- SD age, 75.3 +/- 6.0 years) who received a diagnosis of a current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive episode and were prescribed paroxetine. We monitored plasma sodium levels before initiating paroxetine therapy and after 1, 2, 4, 6, and 12 weeks of treatment. In a subset of individuals, we measured levels of antidiuretic hormone, glucose, serum urea nitrogen, and creatinine. Hyponatremia was defined as a plasma sodium level of less than 135 mEq/L after initiation of paroxetine therapy. RESULTS: Hyponatremia developed in 9 (12%) of the 75 patients after initiation of paroxetine treatment. Mean +/- SD time to development of hyponatremia was 9.3 +/- 4.7 days (median, 9 days; range, 1-14 days; n = 8). In the multivariate regression, lower body mass index and lower baseline plasma sodium level (<138 mEq/L) were significant risk factors for the development of hyponatremia in these patients. CONCLUSIONS: Hyponatremia is an under recognized and potentially serious complication of paroxetine treatment in older patients. Our results provide a foundation for understanding the etiology and risk factors associated with paroxetine-induced hyponatremia.

Aged↗

PubMed2004

The nature and determinants of neuropsychological functioning in late-life depression.

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Age Factors↗

PubMed2004

Adverse effects of depression and cognitive impairment on rehabilitation participation and recovery from hip fracture.

OBJECTIVES: This study examines the effects of depression and cognitive impairment in elderly hip fracture patients receiving inpatient rehabilitation. Our goal was to determine whether any association of depression and cognitive impairment with rehabilitation outcome is accounted for by more immediate effects of these variables on rehabilitation participation. METHODS: We measured depression using the Hamilton Rating Scale for Depression (Ham-D), cognition using the Mini Mental State Examination (MMSE), and rehabilitation outcomes using the motor scale of the Functional Independence Measure (motor FIM) in a prospective observational study of 57 elderly rehabilitation hospital patients admitted to a university-affiliated, freestanding rehabilitation hospital with primary diagnosis of hip fracture. We also assessed rehabilitation participation, to determine whether this accounted for (mediated) any relationship of depression and cognitive impairment with rehabilitation outcome. RESULTS: Baseline Ham-D and MMSE scores were correlated with motor FIM efficiency-those with higher depressive symptoms had lower efficiency (r = -0.44, p < 0.001); similarly, those with more cognitive impairment had lower motor FIM efficiency (r = 0.52, p < 0.001). Rehabilitation participation was a mediator of this association: greater depressive symptoms and cognitive impairment predicted poorer rehabilitation participation which, in turn, predicted lower motor FIM efficiency. Ham-D and MMSE scores were predictors of discharge location: subjects with high depressive symptoms and greater cognitive impairment were more likely to go to a nursing home or personal care home upon discharge. CONCLUSIONS: Depression and cognitive impairment are predictive of negative outcomes in elderly patients' rehabilitation from hip fracture. This effect is mediated by rehabilitation participation, and ratings in this area may serve as a potentially useful clinical and research tool for the rehabilitation environment.

Aged↗

PubMed2004

Neuropathologic correlates of late-onset major depression.

Late life major depression (LLMD) is frequently associated with cognitive impairment, and increases the risk for subsequent dementia. Cerebrovascular disease, Alzheimer's disease (AD), and dementia with Lewy bodies (DLB) have all been hypothesized to contribute to this increased risk, though prospective studies have yet to examine these hypotheses with autopsy confirmation of the clinical diagnoses. The aim of this study is to examine the rates of cerebrovascular, AD, and DLB pathology among the first 10 participants in an LLMD brain tissue donation program. Subjects' psychiatric diagnoses and cognitive status were prospectively determined during their participation in clinical research protocols of the Intervention Research Center for Late Life Mood Disorders. After death, final clinical diagnoses were made using all clinical information, while blind to neuropathologic diagnoses. Neuropathologic assessments were conducted blind to final clinical diagnoses. Rates of neuropathology were compared with those in a cohort of subjects with dementia, without a history of LLMD, participating in an Alzheimer Disease Research Center. Seven (70%) subjects had evidence of onset of a dementia prior to death. LLMD with dementia was significantly associated with a neuropathologic diagnosis of AD. Cerebrovascular disease and DLB pathology were also frequent in the LLMD subjects with dementia, and were found in an LLMD subject without dementia. Rates of AD, DLB, and cerebrovascular disease were similar to those in the comparison subjects. These preliminary findings suggest that AD is the predominant neuropathologic condition in LLMD subjects with dementia. Further assessment of the role of comorbid cerebrovascular disease and comorbid DLB is needed.

Adult↗

PubMed2004

Serotonin 1A receptor binding and treatment response in late-life depression.

Depression in late life carries an increased risk of dementia and brittle response to treatment. There is growing evidence to support a key role of the serotonin type 1A (5-HT(1A)) receptor as a regulator of treatment response, particularly the 5-HT(1A) autoreceptor in the dorsal raphe nucleus (DRN). We used [11C]WAY 100635 and positron emission tomography (PET) to test our hypothesis that 5-HT(1A) receptor binding in the DRN and prefrontal cortex is altered in elderly depressives and that these measures relate to treatment responsivity. We studied 17 elderly subjects with untreated (nonpsychotic, nonbipolar) major depression (four men, 13 women; mean age: 71.4+/-5.9) and 17 healthy control subjects (eight men, nine women; mean age: 70.0+/-6.7). Patients were subsequently treated with paroxetine as part of a clinical trial of maintenance therapies in geriatric depression. [11C]WAY 100635 PET imaging was acquired and binding potential (BP) values derived using compartmental modeling. We observed significantly diminished [11C]WAY 100635 binding in the DRN in depressed (BP = 2.31+/-0.90) relative to control (BP = 3.69+/-1.56) subjects (p = 0.0016). Further, the DRN BP was correlated with pretreatment Hamilton Depression Rating Scores (r = 0.60, p = 0.014) in the depressed cohort. A trend level correlation between DRN binding and time to remission (r = 0.52, p = 0.067) was observed in the 14 depressed patients for whom these data were available. Our finding of decreased [11C]WAY 100635 binding in the brainstem region of the DRN in elderly depressed patients supports evidence of altered 5-HT(1A) autoreceptor function in depression. Further, this work indicates that dysfunction in autoreceptor activity may play a central role in the mechanisms underlying treatment response to selective serotonin reuptake inhibitors in late-life depression.

Aged↗

PubMed2004

Depression after stroke: a prospective epidemiological study.

OBJECTIVES: To elucidate the relationship between stroke and depressive symptoms and to determine whether disability or cerebrovascular risk factors mediate that relationship. DESIGN: A prospective longitudinal epidemiological survey. SETTING: The mid-Monongahela Valley, a rural, nonfarm, low-socioeconomic-status community. PARTICIPANTS: Random sample of 1,134 subjects aged 65 and older. MEASUREMENTS: The dependent variable was clinically significant depressive symptoms, as defined by five or more symptoms on the modified Center for Epidemiological Studies Depression scale. The independent variables were demographics (age, sex, education), stroke, number of impaired instrumental activities of daily living (IADLs), diabetes mellitus, hypertension, atherosclerotic heart disease, and smoking. Logistic regression analyses were conducted for cross-sectional and longitudinal models examining whether stroke was associated with or predicted depressive symptoms, with other associated factors included as covariates. RESULTS: Clinically significant depressive symptoms were cross-sectionally associated with stroke (odds ratio (OR)=3.5, 95% confidence interval (CI)=1.4-8.3), diabetes mellitus (OR=2.8, 95% CI=1.7-4.6; P</=.05), and IADL impairment (OR=1.6, 95% CI=1.4-1.8; P<.05). Longitudinal analysis demonstrated that stroke (OR=6.3, 95% CI=1.7-23.2) and depressive symptoms at baseline (OR=15, 95% CI=7.7-29.5) predicted subsequent clinically significant depressive symptoms measured 2 years later, whereas education was protective (OR=0.4, 95% CI=0.2-0.8). CONCLUSION: Stroke survivors have a greatly elevated risk for clinically significant depressive symptoms even 2 or more years after index stroke, independent of functional disability, cerebrovascular risk factors, and previous depressive symptoms.

Activities of Daily Living↗

PubMed2004

Actors' portrayals of depression to test interrater reliability in clinical trials.

OBJECTIVE: This study determined if actors could portray depressed patients to establish the interrater reliability of raters using the Hamilton Depression Rating Scale (HDRS). METHOD: Actors portrayed depressed patients using scripts derived from HDRS assessments obtained at three points during treatment. Four experienced raters blindly viewed videotapes of two patients and two actors. They guessed if each interviewee was a patient or an actor and rated the certainty of their guesses. For each interview, they also rated the realism of the portrayal and completed the HDRS. RESULTS: Experienced raters could not distinguish actors and patients better than chance and were equally certain of their right and wrong guesses. Actors and patients received high scores on the realism of their portrayals. The HDRS scores of the actor-patient pairs were correlated. CONCLUSIONS: Actors can effectively portray depressed patients. Future studies will determine if actors can accurately portray patients with anxiety and psychosis.

Clinical Trials as Topic↗

PubMed2004

Clinical outcome of ECT in patients with major depression and comorbid borderline personality disorder.

OBJECTIVE: Previous research suggests that the comorbidity of major depression with a personality disorder, especially borderline personality disorder, is associated with a poorer response to ECT. The authors compared the acute outcome of ECT in depressed patients with borderline personality disorder, with personality disorders other than borderline personality disorder, and with no personality disorder. METHOD: The study subjects were 139 patients with a primary diagnosis of unipolar major depression and scores of at least 20 on the 24-item Hamilton Depression Rating Scale. Patients were treated with suprathreshold right unilateral or bilateral ECT in a standardized manner and were assessed with the Hamilton depression scale within 3 days and 4-8 days after completing ECT. RESULTS: Compared to patients with personality disorders other than borderline personality disorder (N=42) and those with no personality disorder (N=77), patients with borderline personality disorder (N=20) had less symptomatic improvement assessed up to 8 days after ECT. Patients with personality disorders other than borderline personality disorder responded as well to ECT as those with no personality disorder. Borderline personality disorder patients were more likely to be female and to have medication-resistant depression than the patients in the two comparison groups; they were also younger. However, none of these differences accounted for the borderline personality disorder patients' poorer response to ECT. CONCLUSIONS: Patients with borderline personality disorder have a poorer acute response to ECT, but explanations for this finding remain elusive.

Adult↗

PubMed2004

Cognitive functioning in late-life bipolar disorder.

OBJECTIVE: This study characterized cognitive functioning in elderly patients with bipolar disorder. METHOD: The cognitive functioning of 18 euthymic patients with a history of bipolar disorder I or II, ages 60 years and older, was tested with the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale, and the Executive Interview. Cognitive functioning in these subjects was compared with that of an age- and education-matched group of 45 comparison subjects without mood disorders. RESULTS: Approximately half of the bipolar subjects scored one or more standard deviations below the mean of the comparison subjects on the MMSE (N=8, 44%) and the Mattis Dementia Rating Scale total (N=10, 56%). On the Executive Interview, three subjects (17%) scored between one and two standard deviations below the mean of the comparison subjects. CONCLUSIONS: A significant proportion of older bipolar subjects exhibited neuropsychological deficits when they were clinically euthymic.

Aged↗

PubMed2004

Concurrent psychiatric diagnoses by age and race among persons with bipolar disorder.

The authors characterized concurrent psychiatric diagnoses among patients with a diagnosis of bipolar disorder who were in routine care by using administrative data from a Department of Veterans Affairs facility. Of 813 patients who had a diagnosis of bipolar disorder in 2000, 21 percent were older (>/=60 years) whites, and 2 percent were older African Americans. Older African Americans were the most likely to have a diagnosis of schizophrenia documented in the medical record compared with younger African Americans, older whites, and younger whites (67 percent, 34 percent, 38 percent, and 27 percent, respectively). The results suggest that older African-American patients with bipolar disorder are more likely to receive diagnoses of mutually exclusive conditions, such as schizophrenia, and thus appear to have an elevated risk of their illness being underrecognized or misdiagnosed and receiving inappropriate treatment.

Aged↗

PubMed2004

Time course of response to antidepressants in late-life major depression: therapeutic implications.

In the treatment of depression, there is considerable interest in the time course of response and, in particular, the speed with which individuals recover from depressive episodes. Examination of the time course and speed of response is critical for assessing the usefulness of specific treatments. However, while this issue has received attention in mid-life adult populations, it has received little consideration in the context of late-life major depression. The synthesis of empirical reports indicates that, while older adults with depression seem to respond with the same speed as mid-life adults, several factors have consistently been associated with reduced speed of response to antidepressant treatment, including greater severity of depressive symptoms and co-occurring anxiety symptoms. Limited evidence suggests that sleep impairment and genetic factors (e.g. presence of the s allele of the serotonin transporter gene promoter region) may also be associated with reduced speed of response. Some factors have consistently been found to be unrelated to speed of response (demographic characteristics, nonpsychiatric physical illnesses) whereas other factors have only mixed evidence supporting any effect (psychosocial and other clinical factors). While there is little work available to date, some evidence suggests that time course and speed of response affect longer-term outcomes of depression pharmacotherapy; thus, older adults with more rapid versus slower patterns of response may differ in the types of maintenance treatment needed to avert additional depressive episodes. None of potential strategies for accelerating speed of response have been clearly shown to be effective in late-life depression. Future treatment studies for late-life depression should routinely consider not only overall efficacy of a given pharmacotherapy (i.e. total rate of response), but time course and speed of response. To this end, new investigations must be designed to overcome the methodological limitations of prior studies that have examined time course and they should include a range of potential covariates and outcomes of between-patient differences in speed of response. Better understanding of factors related to such differences may suggest new intervention strategies to accelerate response.

Aged↗

PubMed2004

Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors.

BACKGROUND: Up to a third of elderly patients with major depressive disorder are treatment resistant, yet little objective evidence is available to guide the clinician in managing these patients. We report here our experience with elderly subjects with prospectively defined treatment-resistant depression in 2 separate research studies: one entailing an augmentation strategy, the other a change to venlafaxine extended release (XR). METHOD: Fifty-three elderly subjects with major depressive disorder according to DSM-IV criteria who failed treatment with paroxetine plus interpersonal psychotherapy received 1 to 3 trials of augmentation with bupropion sustained release, nortriptyline, or lithium. Successively fewer subjects entered each sequential trial of augmentation. Twelve subjects subsequently received venlafaxine XR monotherapy. Response to treatment was defined as a 17-item Hamilton Rating Scale for Depression score of < 10 for 3 weeks. RESULTS: Sixty percent of subjects (N = 32) responded to some form of augmentation, with 45% (24/53), 31% (5/16), and 43% (3/7) responding to the first, second, and third augmentation trials, respectively. The mean time to response after starting the first augmentation trial was 6.0 (SD = 5.8) weeks. Forty-two percent (N = 5) of the venlafaxine XR-treated subjects responded with the mean time to response of 6.4 (SE = 0.9) weeks. Adverse effects leading to treatment discontinuation and falls were more common in the augmentation subjects than in the venlafaxine XR subjects. CONCLUSION: We observed similar rates and speed of response with an augmentation strategy and a strategy of switching to venlafaxine XR in elderly subjects with prospectively defined treatment-resistant major depressive disorder. Venlafaxine XR was generally better tolerated than the augmentation strategies. Further investigation of venlafaxine XR as a preferred strategy for treatment-resistant geriatric depression is warranted.

Aged↗

PubMed2004

Correlates of anticholinergic activity in patients with dementia and psychosis treated with risperidone or olanzapine.

BACKGROUND: Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade. STUDY DESIGN: This was a 6-week multisite, randomized clinical trial. SUBJECTS: Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone. ASSESSMENTS: Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales. RESULTS: There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior. IMPLICATIONS: Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.

Antipsychotic Agents↗

PubMed2003

Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance.

BACKGROUND: Serum anticholinergic activity (SAA), as measured by a radioreceptor assay, quantifies a person's overall anticholinergic burden caused by all drugs and their metabolites. In several small geriatric patient groups, SAA has been associated with cognitive impairment or frank delirium. To our knowledge, there has not yet been any systematic study of the prevalence of SAA and its effect on cognition in a community-based population. METHODS: Serum anticholinergic activity was measured in 201 subjects who were randomly selected among the participants in an epidemiological community study, based on their age and sex. Cognitive performance was assessed with use of the Mini-Mental State Examination. The association between SAA and cognitive performance was examined using a univariate analysis and a multiple logistic regression model, adjusting for age, sex, educational level, and number of medications. RESULTS: Serum anticholinergic activity was detectable in 180 (89.6%) participants (range, 0.50-5.70 pmol/mL). Univariate testing showed a significant association between SAA and Mini-Mental State Examination scores. Logistic regression analysis indicated that subjects with SAA at or above the sample's 90th percentile (ie, SAA >/=2.80 pmol/mL) were 13 times (odds ratio, 1.08-152.39) more likely than subjects with undetectable SAA to have a Mini-Mental State Examination score of 24 (the sample's 10th percentile) or below. CONCLUSIONS: To our knowledge, this is the largest analysis of SAA and the first to examine its extent and relationship with cognitive performance in a community sample. Its results suggest that SAA can be detected in most older persons in the community and confirm that even low SAA is associated with cognitive impairment.

Age Factors↗