Biomedical subjects

Bruce G Pollock

Publications and source records attributed to Bruce G Pollock.

At least 37 records · Page 2Linked to original sources

PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Does education moderate neuropsychological impairment in late-life depression?

OBJECTIVE: The increased resistance of better-educated individuals to the cognitive effects of neuropathology has been conceptualized as reflecting brain reserve. This study examined whether educational level influences the degree of neuropsychological impairment associated with late-life depression. METHODS: The neuropsychological performances of 115 older depressed patients and of 44 comparison subjects of similar age and education were compared as a function of educational level. RESULTS: While depressed patients performed worse than comparison subjects on all the measures, the severity of this impairment (with respect to comparison subjects) did not differ with the educational level of the patients. CONCLUSIONS: Brain reserve, as indexed by the patients' level of education, does not mitigate the cognitive decrements associated with late-life depression.

Aged↗

PubMed2005

Late-onset major depression: clinical and treatment-response variability.

OBJECTIVE: To explore clinical and treatment-response variability in late-onset vs early-onset non-bipolar, non-psychotic major depression. METHODS: We grouped patients from a late-life depression treatment study according to illness-course characteristics: those with early-onset, recurrent depression (n = 59), late-onset, recurrent depression (n = 27), and late-onset, single-episode depression (n = 95). Early-onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late-onset was defined as having a first episode of major depression at age 60 or later. We characterized the three groups of patients with respect to baseline demographic, neuropsychological, and clinical characteristics, use of augmentation pharmacotherapy to achieve response, and treatment outcomes. RESULTS: Rates of response, remission, relapse, and termination were similar in all three groups; however, patients with late-onset, recurrent major depression took longer to respond to treatment than those with late-onset, single-episode depression (12 weeks vs 8 weeks) and had more cognitive and functional impairment. Additionally, patients with recurrent depression (whether early or late) were more likely to require pharmacotherapy augmentation to achieve response than patients with a single lifetime episode. CONCLUSION: Late-onset, recurrent depression takes longer to respond to treatment than late-onset single-episode depression and is more strongly associated with cognitive and functional impairment. Further study of biological, neuropsychologic, and psychosocial correlates of late-onset, recurrent depression is needed.

Activities of Daily Living↗

PubMed2005

Comorbid anxiety disorder in late life depression: association with memory decline over four years.

OBJECTIVE: In elderly persons with Major Depressive Disorder (MDD), coexisting Generalized Anxiety Disorder (GAD) or Panic Disorder (PD) is associated with more severe symptoms and poorer short-term treatment outcomes. The purpose of this study was to determine whether comorbid GAD or PD was associated with poorer long-term outcomes of late-life MDD, in terms of symptoms, functional disability, and cognitive status. METHODS: Seventy-nine older subjects with major depressive disorder who had responded to initial treatment in clinical trials were followed at yearly intervals for up to four years with assessment of their symptoms, cognitive status, and functional disability. For this analysis, subjects were divided into two groups, anxious and non-anxious, based on presence (n = 37) or absence (n = 42) of a lifetime diagnosis of GAD and/or PD. RESULTS: The anxious group showed a greater decline in memory, but not in other cognitive measures or measures of functional status. Depression recurrence was similar in the anxious and non-anxious groups. Among those in the anxious group, a later age of onset (> 55) of the anxiety disorder was associated with worse overall cognition at baseline, but a similar rate of decline in cognition over time, compared with early-onset anxiety disorder. CONCLUSION: We found evidence that comorbid GAD or PD is associated with a greater decline in memory in late-life MDD. The data also suggest that anxiety disorders with an onset later in life may be associated with cognitive impairment, although further study is needed to confirm this finding.

Aged↗

PubMed2005

Dextromethorphan-induced delirium and possible methadone interaction.

INTRODUCTION: Dextromethorphan is a commonly used antitussive agent that can be purchased over the counter. It is metabolized primarily by the cytochrome P450 (CYP) 2D6 isozyme. Methadone has been found to inhibit CYP2D6, indicating a potential for interaction with dextromethorphan. CASE SUMMARY: An 83-year-old woman was evaluated for delirium, hypersomnia, confusion, lethargy, impaired concentration, and poor food intake. Symptoms resolved soon after discontinuing dextromethorphan. DISCUSSION: Vulnerability to delirium was potentially caused by coadministration of methadone, which can inhibit the CYP2D6 isozyme. CONCLUSION: Evaluation of delirium should include close investigation of the patient's medications for potential interactions with dextromethorphan.

Aged↗

PubMed2005

Population pharmacokinetics as a method to detect variable risperidone exposure in patients suffering from dementia with behavioral disturbances.

OBJECTIVE: This study was intended to compare the consistency of risperidone exposure in patients who have dementia and behavioral disturbances treated in a psychiatric hospital versus a community care setting. METHODS: Population pharmacokinetic modeling was used to assess the consistency of risperidone exposure in Alzheimer's disease patients with agitation. The ratio of predicted to observed drug concentrations (Cpred/Cobs) derived from this model was used to compare exposure in the inpatient versus long-term/home care settings using both the mean and the variance of this term across groups. RESULTS: The modeled Cpred/Cobs ratios had a much higher within-subject variance in the inpatients than in the community care patients (117.03% vs 72.35%; P < 0.001). The central tendencies of the Cpred/Cobs ratios across the 2 groups were not significantly different. CONCLUSIONS: Exposure to risperidone was more variable in a psychiatric hospital than in a community care setting. Future research may help to identify the specific contributors to the increased variance observed in this pilot study.

Aged↗

PubMed2005

Trajectories of treatment response in late-life depression: psychosocial and clinical correlates.

The authors examined the effect of psychosocial and clinical variables on treatment response trajectory in elderly patients with major depressive disorder. Three studies provided data on treatment response in 360 elderly depressed subjects who participated in protocols using either nortriptyline or paroxetine as monotherapy or, in 2 studies, combined with interpersonal psychotherapy. Treatment response was assessed with the Hamilton Rating Scale for Depression-17 Item (HRSD-17) score over 12 weeks of acute treatment in each study. The mixture-modeling method of trajectory analysis was used to identify different subpopulations of response, and to determine whether baseline HRSD-17 score, depressive illness course (single or recurrent), current episode duration, Interpersonal Self Evaluation List-Self-esteem factor, age at study entry, and medical burden were risk factor covariates associated with response trajectory. As a contrast, logistic regression was used to assess the association between the same covariates and the probability of response (defined as HRSD-17 < or =10 and 50% reduction from baseline). In each study, there were 2 response trajectories with similar course, but with different speed. We classified the trajectories as "rapid response" and "slower response." Baseline HRSD-17 score was a significant predictor of response trajectory, with higher initial score related to slower response trajectory. Higher self-esteem was associated with more rapid response trajectory. In the logistic regression analysis, in two of the studies, higher baseline HRSD-17 score was a significant risk factor for nonresponse. In the study without psychotherapy, higher self-esteem was associated with responding to treatment. Thus, trajectory analysis can identify different trajectories of responders and determine psychosocial and clinical variables associated with response trajectory in the acute treatment of geriatric depression. Further study focusing on risk factors associated with slower response may help optimize treatment in elderly patients who do not respond quickly to first-line therapies.

Age Factors↗

PubMed2005

The pharmacokinetic imperative in late-life depression.

Older patients frequently have a high burden of medical illness, are subject to extensive medication regimens, and often experience adverse drug events. In general, pharmacokinetic changes associated with aging result in higher and more variable drug concentrations in older patients. Nonetheless, available information on pharmacokinetics of antidepressants is inadequate particularly with regard to medical subgroups and potential drug interactions. Although age-associated pharmacodynamic changes appear to make older patients more sensitive to side effects of antidepressants, differences in pharmacodynamics are not interpretable in the absence of drug concentration data. Population pharmacokinetics provides a means for assessing antidepressant drug exposure with relative ease and precision in clinical trials.

Age Factors↗

PubMed2005

Assessment of geriatric information on the drug label for commonly prescribed drugs in older people.

Older people contribute to a significant portion of all prescription drug use and expenditures in the United States. Despite this, older people are often excluded from clinical trials examining the safety and efficacy of drugs. It is unclear to what extent drugs commonly used in older people contain information about prescribing in older people on their product labeling. The objective of this study was to determine the availability of pharmacokinetic, safety, and dosing information with reference to older people on product labels or package inserts (PIs) for commonly prescribed drugs in patients aged 65 and older. The top 50 oral drugs prescribed at the University of Pittsburgh Medical Center were identified through a computerized search of pharmacy records. PIs for these drugs were evaluated for information on elderly patients. Information on drug use in older people was found in 41 (82%) of the PIs. Drugs marketed after 1990 were more likely to contain information on geriatric use, with pharmacokinetic information being the most common type. Approximately 50% of the PIs contained precautionary statements for older people, but most did not provide any specific problems that might be encountered in this population. Only 28 (56%) PIs had dosing information available, and of these, just eight provided specific milligram recommendations for elderly patients. This analysis provides evidence that more should be done to improve the availability of prescribing information, particularly dosing and safety, on drug labels for older people. Additional regulatory action requiring this information to be included on drug product labels may be warranted.

Aged↗

PubMed2005

Development of a short form of the Severe Impairment Battery.

OBJECTIVE: The authors sought to develop a short form of the Severe Impairment Battery (SIB). METHODS: Authors describe the development of an empirically-derived short form of the SIB (SIB-S) by use of data from 191 subjects with severe dementia in the United States and France. RESULTS: Mean (standard deviation) Mini-Mental State Exam scores for the American and French samples were 7.7 (4.8) and 5.7 (3.4), respectively, and original SIB scores were 71.87 (18.34) and 58.38 (26.86), respectively. Exploratory factor analyses were conducted separately and in combination for the two samples, to determine the number of clinically meaningful factors. An eight-factor model, explaining 60.2% of the common variance, was selected. The eight constructs were described as: expressive language, memory (verbal and nonverbal), social interaction, color-naming, praxis, reading and writing, fluency, and attention. Derived SIB-S scores were 38.41 (9.12) and 29.79 (13.17) for the American and French samples, respectively. CONCLUSIONS: The original SIB is a valid and reliable research tool developed to enable reliable assessment of patients with severe dementia; it takes approximately 30 minutes to administer. The SIB-S takes only 10-15 minutes to administer, making it more appropriate for use in patients with very severe dementia, while it maintains the attributes of the original SIB.

Aged↗

PubMed2005

Accelerating symptom-reduction in late-life depression: a double-blind, randomized, placebo-controlled trial of sleep deprivation.

OBJECTIVE: Authors tested the hypothesis that one night of total sleep deprivation (TSD) would accelerate antidepressant response to paroxetine, as compared with TSD+placebo (PBO) and paroxetine-alone, in late-life major depression. METHODS: Eighty elderly outpatients with current episodes of non-psychotic, non-bipolar major depression were randomly assigned to one of three treatment conditions: TSD+paroxetine (N = 27), TSD + PBO (N = 27), and paroxetine-only (N = 26). Primary outcome was percentage of subjects in each condition who demonstrated early response (Hamilton Rating Scale for Depression scores [Ham-D: 17-item] of < or = 10) or remission (score of < or = 7) on Day 14. RESULTS: Response rates after 14 days were 22% in subjects randomly assigned to the TSD + paroxetine condition, 41% in TSD + PBO, and 46% in paroxetine alone. Remission rates after 14 days were 11% in TSD+paroxetine, 22% in TSD + PBO, and 38% in paroxetine. After adjusting for baseline depression severity, there were no statistically significant differences in response or remission rates. CONCLUSION: Contrary to the study hypothesis, one night of total sleep deprivation did not accelerate onset of antidepressant response to paroxetine pharmacotherapy of late-life depression. The data suggest, rather, that the two interventions might have counteracted each other.

Aged↗

PubMed2005

Association of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) genotype with depression in elderly persons after hip fracture.

OBJECTIVE: The authors examined the serotonin transporter gene-linked polymorphic region (5-HTTLPR) as a predictor of major depressive disorder and depressive symptoms after hip fracture, a common stressful medical event. METHODS: This was a prospective, observational study of 23 elderly rehabilitation-hospital patients during their inpatient stay. Depressive symptoms were assessed by Hamilton Rating Scale for Depression (Ham-D) and PRIME-MD. Subjects were also genotyped for 5-HTTLPR. RESULTS: Survival analysis showed that genotype significantly predicted time-to-major depressive episode. Subjects with an s allele (genotype s/l or s/s) had significantly higher Ham-D scores over 14 weeks of follow-up than those with the l/l genotype. CONCLUSION: Depressive symptoms and major depressive disorder in elderly persons after a stressful medical event may be associated with 5-HTTLPR genotype. This finding requires confirmation in a larger sample.

Aged↗

PubMed2005

Serum anticholinergic activity and cognition in patients with moderate-to-severe dementia.

OBJECTIVE: The authors investigated the association between serum anticholinergic activity (SAA) and cognitive performance in a group of patients with moderate-to-severe dementia. METHODS: SAA and cognitive performance were assessed in 26 patients admitted to a geropsychiatric unit for the treatment of behavioral disturbances associated with dementia. SAA was measured by radioreceptor competitive binding assay. Cognition was tested with the Mini-Mental State Exam and the Severe Impairment Battery. RESULTS: Higher SAA was associated with lower cognitive performance. CONCLUSION: This study extends to patients with moderate-to-severe dementia the finding that higher SAA is associated with lower cognitive performance.

Aged↗

PubMed2005

Efficacy and tolerability of citalopram in the treatment of late-life anxiety disorders: results from an 8-week randomized, placebo-controlled trial.

OBJECTIVE: Anxiety disorders are highly prevalent in elderly persons. However, to date, the efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety disorders in this age group has not been established. METHOD: Thirty-four participants age 60 and older with a DSM-IV anxiety disorder (mainly generalized anxiety disorder) and a Hamilton Anxiety Rating Scale score of 17 or higher were randomly assigned under double-blind conditions to either citalopram or placebo. Response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Improvement scale or a 50% reduction in the Hamilton anxiety scale score. Response and side effects with citalopram and placebo were compared by using chi-square tests and linear modeling. RESULTS: Eleven (65%) of the 17 citalopram-treated participants responded by 8 weeks, versus four (24%) of the 17 placebo-treated participants. The most common and problematic side effect in the citalopram group was sedation. CONCLUSIONS: The authors believe this to be the first prospective controlled study to test the efficacy of an SSRI in the management of anxiety disorders among the elderly. These results support the efficacy of citalopram in late-life anxiety disorders. They need to be replicated in a larger study group.

Age Factors↗

PubMed2005

Aging and clinical pharmacology: implications for antidepressants.

The elderly frequently have changes in pharmacokinetics, sensitivity to medications, homeostatic reserve (ability to tolerate physiological challenges), exposure to multiple medications, and adherence. All of these age-associated factors can potentially influence total exposure to medication, adverse effects, and subsequent treatment outcome. Most clinical trials are performed with healthy, younger adults. Extrapolating the results of these trials to the elderly may be inappropriate, particularly for the antidepressant treatment of depression. The authors review these age-associated differences and discuss their implications for antidepressant use in older adults.

Adult↗

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

Neuroendocrine response to intravenous citalopram in healthy control subjects: pharmacokinetic influences.

RATIONALE: The neuroendocrine response to intravenous citalopram may provide an acute, functional, in vivo measure of the neural serotonin (5-HT) system. OBJECTIVE: To refine the quantification of acute neuroendocrine responses following intravenous citalopram in studies of 5-HT function. METHODS: In 75 adult healthy subjects taking part in four similar protocols, we measured plasma prolactin and cortisol, as well as serial citalopram concentrations following intravenous citalopram (10 mg, 20 mg, 40 mg, 0.33 mg/kg) and placebo. The relationship between the AUC for intravenous citalopram during the first 150 min (AUC(150)) and the magnitude of the neuroendocrine response was determined. The role of pharmacokinetic (PK) parameters, as well as sensitivity to placebo injections, in influencing the neuroendocrine response to citalopram was then evaluated. RESULTS: Citalopram produced a dose-dependent increase in cortisol and prolactin. The maximal increase from baseline correlated significantly but modestly with citalopram's AUC(150) (prolactin r(2)=0.23, P<0.0001; cortisol r(2)=0.3, P<0.0001). Additionally, citalopram's AUC(150) was affected by between-subject differences in both the peripheral and central volume of distribution. However, the neuroendocrine responses to citalopram did not correlate with the responses to placebo. CONCLUSIONS: The parenteral citalopram challenge test is characterized by a modest concentration-response relationship, with concentration influenced by variable PK factors. Accounting for individual differences in drug distribution may improve the power of the citalopram challenge test, when used as an in vivo measure of central 5-HT function.

Adult↗

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↗