Biomedical subjects

B H Mulsant

Publications and source records attributed to B H Mulsant.

At least 73 records · Page 4Linked to original sources

PubMed1997

The relationship between self-rated health and depressive symptoms in an epidemiological sample of community-dwelling older adults.

OBJECTIVE: To confirm the association between depression and self-rated general health, independent of demographics, functional disability, physical illness burden, and health services utilization. DESIGN: Logistic regression analyses of data obtained in a cross-sectional epidemiological survey. SETTING: The mid-Monongahela Valley, a rural, nonfarm, low SES community. PARTICIPANTS: Random sample of 880 subjects aged 65 and older. MEASUREMENTS: The dependent variable was self-rated overall health, categorized as excellent, good, fair, or poor. The independent variables were demographics (age, gender, education), number of depressive symptoms, number of impaired instrumental activities of daily living (IADLs), measures of physical illness burden (individual medical conditions, number of affected organ systems or disease processes, and number of prescription medications), and measures of health services utilization (number of visits to physicians, and acute hospitalization). RESULTS: Univariate analyses indicated that poorer self-rated health was associated with lesser education, higher numbers of depressive symptoms, impaired IADLs, prescription medications, physician visits, hospitalizations, and affected organ systems, and with the presence of several specific conditions. However, multiple logistic regression analyses revealed that only the following variables were associated independently with poorer self-rated health: age less than 75 years, education less than high school graduation, greater numbers of depressive symptoms, impaired IADLs, prescription medications, and physician visits. CONCLUSIONS: Even when controlling for physical illness and functional disability, subjective rating of overall health remains strongly and independently associated with depressive symptoms.

Activities of Daily Living↗

PubMed1997

Mortality of elderly patients with psychiatric disorders.

OBJECTIVE: The goal of this study was to evaluate the impact of common late-life mental disorders on the life expectancy and causes of death of older psychiatric patients. METHOD: The study population consisted of 809 older psychiatric patients who met DSM-III-R criteria for organic mental disorders, mood disorders, or psychotic disorders and who were discharged after a comprehensive multidisciplinary evaluation and acute inpatient treatment for their behavioral disorders. Dates and causes of death during a 5.75-year follow-up period were provided by the Pennsylvania Department of Health. Univariate and multivariate survival procedures were used to compare the survival rates of the three groups to each other and to a reference population of Pennsylvania residents. Causes of death were also tabulated according to ICD-9-CM and compared across the groups. RESULTS: Age, gender, race, and medical comorbidity made significant independent contributions to survival. When these variables were controlled, the survival of patients with organic mental disorders was less than half of that for patients with mood or psychotic disorders. However, all three groups experienced higher rates of mortality than the reference population, with standardized mortality ratios of 1.5 to 2.5. Deaths occurred from the usual spectrum of natural causes, with the exception that patients with mood disorders were more likely to have died from disorders of the digestive system and suicide. CONCLUSIONS: The mental disorders of late life have a significant negative impact on the survival of older psychiatric patients.

Age Factors↗

PubMed1997

Low use of neuroleptic drugs in the treatment of psychotic major depression.

OBJECTIVE: The adequacy of pharmacologic treatment received by patients with psychotic major depression was evaluated. METHOD: The authors systematically assessed the pharmacotherapy received by 187 depressed patients before initiation of ECT and compared the medication trials of those with psychotic (N = 53) and nonpsychotic (N = 134) depression. RESULTS: Despite a median of four medication trials and median index episode duration of 20 weeks, only two (4%) of the patients with psychotic depression received at least one adequate pharmacotherapy trial. In contrast, 70 (52%) of the patients with nonpsychotic depression received at least one adequate trial. Twenty-five (47%) of the patients with psychotic depression received either no neuroleptic treatment (N = 11) or treatment for less than 3 weeks (N = 14). Only eight (15%) received a daily neuroleptic dose higher than 200 mg of chlorpromazine equivalents. CONCLUSIONS: These findings suggest that many patients with psychotic major depression referred for ECT receive inadequate pharmacotherapy because of either the absence or the inadequate use of neuroleptic medication.

Antidepressive Agents↗

PubMed1997

Effect of sertraline on plasma nortriptyline levels in depressed elderly.

BACKGROUND: Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients. METHOD: We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline. RESULTS: After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08). CONCLUSION: Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.

1-Naphthylamine↗

PubMed1997

An open pilot study of citalopram for behavioral disturbances of dementia. Plasma levels and real-time observations.

Citalopram, in European studies, has shown some early promise for treatment of poststroke depression and behavioral complications of dementia. An open pilot study of citalopram was conducted in 16 patients with dementia and behavioral disturbances. Citalopram was well tolerated by 13 of the patients, and 9 had a clinically impressive response. A significant overall mean reduction in disruptive vocalizations was observed by means of a novel technique of computer-assisted real-time observation. The mean citalopram plasma level-to-dose ratio was found to be twice that previously reported in younger patients. These pilot findings should encourage future placebo concentration-controlled trials.

Aged↗

PubMed1997

Methodological issues in characterizing treatment response in demented patients with behavioral disturbances.

Despite the proliferation of instruments developed to rate behavioral disturbances associated with dementia, systematic studies of how ratings on these instruments should be analyzed to measure change in disruptive behaviors or distressing symptoms (ie treatment response) are noticeably absent. Using one of these scales, we compared three methods to characterize treatment response in 52 elderly demented inpatients who participated in a standardized neuroleptic trial. While all three analyses identified a statistically significant improvement, they conveyed differently the clinical improvement experienced by the patients. Categorical outcomes communicated the clinical meaning of improvement better than changes in total score; changes in factor scores best revealed the differential impact of treatment on specific behavioral and symptomatic domains. Given the heterogeneity of the problematic behaviors and symptoms exhibited by demented patients included in treatment trials, regardless of the intervention being tested or of the instrument being used to rate behaviors, a focused approach to characterizing treatment response is needed.

Aged↗

PubMed1997

Low-level serum anticholinergicity as a source of baseline cognitive heterogeneity in geriatric depressed patients.

Depressed geriatric patients show substantial intersubject variability in cognitive performance, which complicates attempts to evaluate the cognitive effects of depression and of antidepressant therapy. This variability may reflect the multiple medications older patients take, many of which have anticholinergic effects. This study examined whether serum anticholinergicity (SA) explained some of the variability in depressed geriatric patients' memory performance. Before starting antidepressant treatment, 36 elderly depressed subjects were given a verbal learning test. At the same time, a blood sample was taken and analyzed by radioreceptor binding assay to determine their SA level. Nineteen of the subjects had detectable levels (mean = 0.28 pmole atropine equivalent). Subjects with an SA of zero showed significantly better delayed recall than did those with a positive SA level. Thus, even very low SA may produce subtle decrements in memory performance, an area of cognition known to be highly sensitive to anticholinergic effects.

Aged↗

PubMed1996

MRI changes in schizophrenia in late life: a preliminary controlled study.

The aim of this pilot study was to compare cerebral changes on magnetic resonance imaging (MRI) scans in elderly schizophrenic subjects with those in psychiatric and normal control subjects. We compared the MRIs of 19 subjects with schizophrenia, 19 age- and gender-matched subjects with recurrent major depression, and 19 age- and gender-matched nonpsychiatric control subjects. Deep white matter hyperintensities (DWMH) in right posterior regions were significantly more prominent in the schizophrenic group than in the two comparison groups. Total ratings of MRI abnormalities were significantly related to age in both the normal control and schizophrenic groups, but not in the depressive group. Age of onset was positively associated with total ratings in the depressive group, but not in the schizophrenic group. Thus, a subset of elderly patients with schizophrenia appear to have cerebral white matter abnormalities; such abnormalities may not be confined to late-onset schizophrenia. Systematic MRI studies of early- and late-onset schizophrenia in late life are needed to resolve this question.

Adolescent↗

PubMed1996

Comorbid anxiety disorders in late-life depression.

We examined the prevalence and correlates of comorbid anxiety disorders in two groups of older depressed patients assessed at the University of Pittsburgh. A total of 336 older outpatients and inpatients with major depression were comprehensively evaluated with several instruments including the Hamilton Depression Rating Scale, and either the SADS-L or the SCID for DSM-III-R. These patients presented with major depression, associated with a wide range of functional, cognitive, and medical impairment. One-third to one-half of them also presented with severe symptomatic anxiety. However, only a small proportion (less than 5%) met diagnostic criteria for lifetime or current panic, obsessive-compulsive, or phobic disorders. At baseline, lifetime comorbid anxiety disorders were associated with a higher rate of alcoholism and higher symptomatic anxiety. Lifetime comorbid anxiety disorders did not affect the rate of response of depression, but they were associated with a higher use of benzodiazepines and a 50% increase in the time outpatients needed to respond. These findings suggest that, even in psychiatric patients with major depression, the lifetime prevalence of anxiety disorders is lower in late life, but that it has important clinical and therapeutic implications.

Aged↗

PubMed1995

Quantitative determination of perphenazine and its metabolites in plasma by high-performance liquid chromatography and coulometric detection.

An accurate, reliable method has been developed for the therapeutic monitoring of perphenazine (PPZ) and its major metabolites in human plasma samples. Steady-state plasma levels of PPZ and its metabolites were quantitated for 30 elderly patients (mean age: 75) undergoing concurrent treatment with nortriptyline (NT) and PPZ, doses ranging from 4 to 32 mg/day for PPZ. The assay was suitable with patients on concurrent medications, and smaller patient plasma volumes (1 ml) were used indicating sufficient sensitivity and specificity. After plasma extraction and separation on a Nucleosil 5-microns C18 column, the recoveries (mean +/- S.D.) of PPZ and its metabolites were determined; perphenazine 92 +/- 7.5%, deshydroxyethylperphenazine 81 +/- 7.2%, perphenazine sulfoxide 68 +/- 6.4%, and 7-hydroxyperphenazine 45 +/- 5.5%. The assay also had limits of quantitative detectability for PPZ and its metabolites as follows: perphenazine 0.5 ng/ml, deshydroxyethylperphenazine 1.0 ng/ml, perphenazine sulfoxide 0.5 ng/ml, and 7-hydroxyperphenazine 5 ng/ml. Inter-assay reproducibility (C.V.) for the quality controls and patient samples ranged from 18.8 to 2.4%. The sensitivity and reproducibility of this method should improve PPZ therapeutic drug monitoring and research on interactions in depressed geriatric patients.

Aged↗

PubMed1995

Duration of neuroleptic treatment and prevalence of tardive dyskinesia in late life.

BACKGROUND: Although increasing age is the most consistently cited risk factor for the development of tardive dyskinesia for patients in the second to sixth decades of life, this relationship may not hold within geriatric populations. METHODS: Consecutively admitted geropsychiatric inpatients were examined with the Abnormal Involuntary Movement Scale within 72 hours of admission; comprehensive demographic, diagnostic, and psychometric data were also obtained. RESULTS: Seventy-four (19.2%) of 386 patients received diagnoses of dyskinesia. Lifetime duration of neuroleptic use was strongly correlated with dyskinesia rates. After accounting for the effect of lifetime duration of neuroleptic use in a stepwise logistic regression, only associations with Global Assessment Scale score and presence of dental problems remained statistically significant. In comparison with the duration of neuroleptic use, however, the contribution of these factors was minor. Sixteen percent of patients with less than 3 months of neuroleptic use, 29% with 3 to 12 months of neuroleptic use, 30% with 1 to 10 years of neuroleptic use, and 41% with more than 10 years of neuroleptic use had dyskinesia. Compared with patients with no history of neuroleptic treatment, the relative risks for these durations of neuroleptic use were 1.62 (95% confidence limits [CL], 0.81, 3.24), 2.89 (95% CL, 1.50, 5.55), 3.08 (95% CL, 1.66, 5.70), and 4.11 (95% CL, 2.12, 7.96), respectively. CONCLUSIONS: Within elderly populations, duration of exposure to neuroleptics is the strongest predictor of risk for tardive dyskinesia, and this risk increases rapidly within the first year of total lifetime neuroleptic use.

Age Factors↗

PubMed1995

Antipsychotics in older patients. A safety perspective.

Age is a major source of variation in drug response. Social, medical and physiological heterogeneity intertwines to complicate geriatric pharmacotherapy. Inappropriate and excessive use of medication may be the most significant treatable health problem in the elderly. Older people are especially sensitive to antipsychotics, which are disproportionately prescribed to them. Antipsychotic side effects and adverse reactions are intensified and protean in an older population, ranging from disabling to deadly. It is therefore essential that the use of antipsychotics be based on clear indications, guided by knowledge of both age-related and individual determinants of drug clearance and action. Prospective and frequent assessments for adverse effects are also essential.

Absorption↗

PubMed1995

Prospective cytochrome P450 phenotyping for neuroleptic treatment in dementia.

Older patients have more adverse experiences when treated with psychotropics than younger patients. Age-associated physiological changes, such as reductions in hepatic mass and blood flow, magnify genetic and acquired variations in drug metabolism. Cytochrome P450 2D6 (debrisoquine hydroxylase), which is responsible for the metabolism of several antidepressants and neuroleptics, is constitutionally deficient in up to 10 percent of the population. In this study of 45 elderly patients suffering from dementia and treated with perphenazine, 5 patients who were prospectively identified as poor P450 2D6 metabolizers had significantly greater side effects than the 40 extensive metabolizers.

Aged↗

PubMed1995

Prolactin response to neuroleptic challenge in late-life psychosis.

Psychosis in the elderly is superimposed on both age-related and disease-specific declines in dopaminergic function. Though the prolactin (PRL) response to neuroleptic challenge has been used as an in vivo measure of dopaminergic function in midlife adults, it remains uninvestigated in late-life psychoses. We examined the PRL response to intravenous perphenazine (PZ) in 11 elderly patients with psychotic symptoms complicating either a major depression (MD-P) or a dementia. The magnitude of increase in prolactin after PZ divided patients into three non-overlapping groups: dementia patients had a bimodal response and MD-P patients fell between the dementia groups. Our findings suggest that the PRL response to PZ may provide an in vivo measure of dopaminergic function in elderly patients. This finding must be confirmed through correlation with other measures of dopaminergic function in late-life psychoses and with measures of neuroleptic response and neuroleptic-induced extrapyramidal effects.

Aged↗

PubMed1995

Double-blind comparison of paroxetine and nortriptyline on the postural stability of late-life depressed patients.

This article describes a 6-week study evaluating body sway during double-blind therapy with nortriptyline versus paroxetine in geriatric patients. Body sway was measured with patients' eyes open, then closed, using a stable force platform at 4 timepoints: before starting antidepressant medication, and after 1, 2, and 6 weeks of treatment. Measures such as the length (L) of path of the center of pressure (COP) and the area included within the COP path were selected for quantitative assessment of stability. A repeated measures analysis of variance (ANOVA) model with planned comparisons was used to examine the pair-wise difference at baseline and Weeks 1, 2, and 6 of treatment. No significant difference was found in body sway parameters over the 6 weeks of study for patients treated with either nortriptyline or paroxetine.

Aged↗

PubMed1995

Risperidone use in a teaching hospital during its first year after market approval: economic and clinical implications.

Risperidone, a new antipsychotic drug, was recently approved by the Food and Drug Administration (FDA) on the basis of its having comparable efficacy and less toxicity than haloperidol. In a preliminary study to evaluate the therapeutic efficiency of this drug, we conducted a survey of resperidone utilization, cost, and safety during its first year of availability at an academic psychiatric hospital. Data were obtained from a computerized, centralized medical record system, from an adverse drug reaction monitoring system, and from pharmacy purchasing records. In its first year of availability, risperidone became the second most widely used antipsychotic agent at our institution. Most of this use extended beyond the adult schizophrenia population, for whom pre-marketing safety and efficacy data are available. The direct institutional cost of risperidone treatment exceeded the entire budget for antipsychotic drugs during the year before its release. Results from the adverse drug reaction reporting system did not indicate a strong advantage of risperidone over more established antipsychotic agents with respect to extrapyramidal side effects. Furthermore, the mean dose of risperidone associated with extrapyramidal symptoms was 3.5 mg/day, considerably lower than that suggested by pre-marketing studies in a more select patient group. These results confirm that new pharmacological agents are generally used in much broader patient populations than those for which efficacy and safety have been established prior to FDA approval. This study also raises questions about the therapeutic efficiency of risperidone compared with other antipsychotic drugs. We conclude that systematic studies of outcome, safety, and cost of new pharmaceuticals in naturalistic settings are needed to provide the data necessary to establish local standards of cost-effective care.

Adolescent↗

PubMed1994

Diagnostic rate of comorbid personality disorder in elderly psychiatric inpatients.

Among 547 elderly inpatients grouped by DSM-III-R axis I diagnoses, the diagnostic rate of comorbid personality disorder varied four-fold, from 6% in patients with an organic mental disorder to 24% in those with major depression. The previously reported low prevalence of comorbid personality disorder in geriatric patients may be due to its lower rate of diagnosis among patients with organic mental disorders.

Aged↗

PubMed1994

Impact of acute psychiatric inpatient treatment on major depression in late life and prediction of response.

OBJECTIVE: The authors conducted a prospective study to examine the sociodemographic and clinical characteristics of elderly inpatients with major depression and their response to acute psychiatric hospitalization. The relation between the descriptive variables and clinical response was also investigated. METHOD: The subjects were 205 consecutively admitted inpatients, whose mean age was 71 years, who met the DSM-III-R criteria for major depression. Each subject received detailed physical, psychiatric, and mental status examinations, along with quantitative assessments of psychiatric symptoms and cognitive performance at admission and at discharge. Management of physical problems was optimized, and patients were treated with a combination of somatic and psychotherapeutic interventions. The average duration of hospitalization was approximately 1 month. RESULTS: Despite considerable medical and psychiatric comorbidity, the patients responded well to treatment, as reflected by a 50% reduction in the average score on the Hamilton Depression Rating Scale. Nearly one-half of the patients had experienced the resolution of their depressive symptoms by the time of discharge. Race, cognitive performance at admission, number of medical problems, use of ECT, and length of hospitalization independently contributed to the prediction of clinical response. Response to treatment was not related to the other sociodemographic variables examined or to any of the indexes of severity of depressive episode. CONCLUSIONS: Short-term psychiatric hospitalization offers an effective and efficient vehicle for the treatment of severe or complicated cases of major depression in the elderly, even when considerable medical and psychiatric comorbidity is present.

Age Factors↗