Biomedical subjects

B H Mulsant

Publications and source records attributed to B H Mulsant.

At least 55 records · Page 3Linked to original sources

PubMed1999

The temporal relationship between depressive symptoms and dementia: a community-based prospective study.

BACKGROUND: The temporal relationship between the appearance of depressive symptoms and the clinical onset of dementia and Alzheimer disease was evaluated in a community sample. METHODS: An original sample of 1366 subjects aged 65 years or older, selected randomly from a rural Pennsylvania community, was cognitively screened at study entry and every 2 years thereafter. A subset of 954 survivors of this cohort without dementia was screened for depressive symptoms at the second and subsequent data-collection waves. A "depression cluster" was identified by the presence of 5 or more depressive symptoms, including depressed mood, at the time of screening. Cognitively impaired subjects and a sample of unimpaired controls underwent standardized clinical evaluation to determine the presence of incident dementia (by DSM-III-R criteria) and probable or possible Alzheimer disease (by criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and to estimate the clinical onset of dementia symptoms. RESULTS: A highly increased probability of the depression cluster developing existed among subjects following the onset of dementia (15.4% [6/39]) and Alzheimer disease (17.6% [6/34]) compared with subjects without dementia (3.2% [23/712]). The odds ratios, after adjustment for age, sex, education level, and self reported memory loss, for the development of depression were 6.5 (95% confidence interval, 2.2-19.1) in subjects with Alzheimer disease and 5.2 (95% confidence interval, 1.8-15.2) in subjects with overall dementia. Depressive symptoms did not confer a significantly increased relative risk of dementia (1.27; 95% confidence interval, 0.55-2.93) or Alzheimer disease (1.28; 95% confidence interval, 0.51-3.20). CONCLUSION: Depressive symptoms appeared to be early manifestations, rather than predictors, of Alzheimer disease in this community sample.

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PubMed1999

Acute efficacy of ECT in the treatment of major depression in the old-old.

OBJECTIVE: There are few data addressing the outcome of ECT for persons over 75 years of age. In a prospective, multisite study, the authors compared characteristics and treatment outcomes of adult (59 and younger), young-old (60 to 74 years), and old-old (75 and older) patients treated with ECT for major depression. METHOD: At four hospitals, 268 patients with primary unipolar major depression and scores of at least 20 on the 24-item Hamilton Depression Rating Scale were treated with suprathreshold right unilateral or bilateral ECT in a standardized manner. Demographic variables, clinical characteristics, and short-term outcomes of the three groups were compared. RESULTS: The demographic and clinical characteristics of the old-old patients were similar to those of the young-old patients, whereas both groups differed from the adult patients on these variables. Both older groups had significantly greater burdens from physical illness and global cognitive impairment at baseline than the adult subjects. Both older groups had shorter index depressive episodes and were less likely to have had inadequate responses to adequate medication trials before ECT. The older groups had higher seizure thresholds, but the three groups received similar courses of treatment. The adult patients experienced a significantly lower rate of ECT response (54%) than the young-old patients (73%), while the old-old patients had an intermediate rate of response (67%). CONCLUSIONS: Despite a higher level of physical illness and cognitive impairment, even the oldest patients with severe major depression tolerate ECT in a manner similar to that for younger patients and demonstrate similar or better acute response.

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PubMed1999

PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders.

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.

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PubMed1999

Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortriptyline, or placebo.

Speed of response is an important clinical issue in the treatment of depressed elderly patients. Our objective was to compare rapid response rates in a study combining therapeutic sleep deprivation (TSD) with paroxetine with two earlier randomized, double-blind studies in late-life depression, one of paroxetine versus nortriptyline and another of nortriptyline versus placebo. We measured depressive symptoms with the 17-item Hamilton Rating Scale of Depression (HRSD), defining rapid response as an HRSD < or = 10 by 2 weeks. With combination therapy (TSD + paroxetine), 9 of 13 patients (69%) experienced a rapid response. In the nortriptyline versus paroxetine study, nortriptyline brought about rapid response in 12 of 37 (32%) and paroxetine in 11 of 43 patients (26%). In the third study, rapid response to nortriptyline occurred in 10 of 41 patients (24%) and to placebo in 6 of 39 patients (15%). The overall chi square, including the rate of rapid response to placebo, was 14.87 (P = .005). The chi square on the four active treatment groups, excluding placebo, was 10.28 (P = .016). This preliminary observation suggests that combined therapy with TSD plus paroxetine may be twice as successful at achieving rapid response in elderly depressed patients than conventional monotherapy with medication or placebo. A prospective, placebo-controlled evaluation of this dual therapy is warranted.

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PubMed1999

Epidemiology and diagnosis of depression in late life.

Depression is a significant concern in elderly patients. Reported prevalence rates differ greatly depending on the definition of depression and the population of interest, with increases reported in settings where comorbid physical illnesses are more common. In community-dwelling elderly patients, prevalences of depressive symptoms and major depressive disorder are 15% and 1% to 3%, respectively. Factors associated with depression in the elderly include female gender, alcohol and substance abuse, pharmaceuticals, family history, and medical conditions such as stroke, Alzheimer's disease, cancer, and heart disease. Recognition of depression is complex because patients often deny their depression, present with somatic complaints, or may have comorbid anxiety or cognitive impairment. Depression is underrecognized and undertreated in the elderly, despite evidence that the benefits of treatment outweigh potential risks.

Age Factors↗

PubMed1999

A double-blind randomized comparison of nortriptyline and paroxetine in the treatment of late-life depression: 6-week outcome.

BACKGROUND: Some studies have suggested that selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The objective of this study was to compare the 6-week outcome of treatment with nortriptyline and paroxetine in older patients with a major depressive episode. METHOD: A double-blind randomized comparison of nortriptyline and paroxetine was conducted in 80 elderly (mean +/- SD age = 75.0 +/- 7.4 years) psychiatric inpatients and outpatients who presented with a major depressive episode. Dropout and response rates were compared in patients who began or completed treatment. Rates of response of inpatients and patients with melancholic depression were also compared. RESULTS: Over 6 weeks, there were no significant differences in dropout rates due to side effects (nortriptyline, 14% vs. paroxetine, 19%) or for any reason (27% vs. 33%). Similarly, there were no significant differences between the rates of favorable response to nortriptyline or paroxetine (intent-to-treat analysis, 57% vs. 44%; completer analysis, 78% vs. 66%). Analyses restricted to inpatients or to patients with melancholic depression yielded similar results. CONCLUSION: Nortriptyline and paroxetine appear to have similar efficacy and tolerability in the acute (6-week) treatment of older depressed patients, including hospitalized patients and those with melancholic features.

Age Factors↗

PubMed1999

Continuation and maintenance pharmacotherapy in geriatric depression: an open-trial comparison of paroxetine and nortriptyline in patients older than 70 years.

We present preliminary data on the efficacy of paroxetine, as compared with nortriptyline, in preventing or delaying relapse and recurrence of major depression in elderly patients. Following double-blind, acute-phase pharmacotherapy, 25 patients (mean age = 72.5 years) began open-trial continuation treatment with paroxetine (mean dose = 24.5 mg/day), and 15 patients (mean age = 77.5 years) received nortriptyline (mean dose = 51.3 mg/day; mean blood level = 85.5 ng/mL). Over an 18-month period, paroxetine and nortriptyline have shown comparable efficacy in preventing or delaying relapse and recurrence, with 80% to 90% of patients remaining well. These data suggest that paroxetine holds promise for long-term maintenance treatment in patients in their 70s and older with depression; however, further controlled evaluation is necessary.

Age Factors↗

PubMed1999

Cognitive effects of paroxetine in older depressed patients.

This study examined whether paroxetine produces cognitive toxicity in elderly patients suffering from a major depressive episode. Twenty-nine depressed patients with a wide range of cognitive functioning were treated with paroxetine. At baseline and during 6 weeks of treatment, patients were asked to complete various measures of cognitive function and had blood drawn to determine serum anticholinergicity. Measures of attention and cognitive speed showed significant improvement with treatment, while the memory performance remained unchanged. A similar pattern of results was found in both cognitively impaired and intact patients. The slight increase in serum anticholinergicity seen in some elderly patients did not significantly impair cognitive function, even in patients with a preexisting cognitive impairment.

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PubMed1999

Age at onset in geriatric bipolar disorder. Effects on clinical presentation and treatment outcomes in an inpatient sample.

The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for bipolar disorder, divided into early- and late-onset groups by their median age at lifetime onset, 49 years, in order to examine differences in demographic and clinical characteristics, treatment parameters, and outcome in the two groups during a short-term hospitalization. The late-onset group was more likely to have psychotic features and to demonstrate cerebrovascular risk/burden. However, both groups had similar and highly significant improvements in the Brief Psychiatric Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87% were able to be discharged to settings no more restrictive than those at admission.

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PubMed1998

Serum anticholinergicity in elderly depressed patients treated with paroxetine or nortriptyline.

OBJECTIVE: The authors' goal was to compare serum anticholinergicity of 61 elderly depressed patients randomly assigned to double-blind treatment with paroxetine (N=31) or nortriptyline (N=30). METHOD: Both antidepressants were titrated in a standardized manner, and plasma was sampled weekly for measurement of paroxetine and nortriptyline and its hydroxy metabolite concentrations. Serum anticholinergicity was measured at baseline and after 1, 4, and 6 weeks of treatment. Side effects were assessed by using a validated scale. RESULTS: After correcting for pretreatment anticholinergicity, the authors found that mean serum anticholinergicity for the nortriptyline-treated patients was significantly greater than that for the paroxetine group at all weeks assessed. Serum anticholinergicity was significantly correlated with nortriptyline but not with paroxetine plasma levels. Complaints of dry mouth and tachycardia were significantly more frequent and severe in the nortriptyline group. CONCLUSIONS: These findings suggest that, at therapeutic plasma concentrations, paroxetine has approximately one-fifth the anticholinergic potential of nortriptyline in older patients.

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PubMed1998

Determinants of spontaneous extrapyramidal symptoms in elderly psychiatric inpatients diagnosed with Alzheimer's disease, major depressive disorder, or psychotic disorders.

Extrapyramidal symptoms (EPS) occur more frequently in dementia of the Alzheimer's type (DAT) than in normal aging. Other late-life mental disorders, however, have also been associated with EPS. To examine whether EPS are increased in DAT patients relative to neuropsychiatric control subjects, the authors compared EPS in 127 neuroleptic-free elderly patients diagnosed with either DAT, major depressive disorder (MDD), or a psychotic disorder (SCHIZ/DELUS). They also examined whether depressive or psychotic symptoms were associated with EPS independently of diagnosis. Severity of parkinsonian rigidity was found to be independently associated with DAT. Rank order of rigidity was DAT > MDD > SCHIZ/DELUS. Bradykinesia, although not associated with diagnostic group, was positively correlated with withdrawn depression. These findings suggest that rigidity is associated with DAT independently of any concurrent psychotic or depressive process, whereas bradykinesia does not appear to be specific to DAT among late-life neuropsychiatric illnesses.

Age Factors↗

PubMed1998

Is delirium different when it occurs in dementia? A study using the delirium rating scale.

The authors studied 61 geropsychiatric patients with delirium from a cohort of 843 consecutive admissions to a geriatric clinical research unit. A central study goal was to assess how the presence of dementia affected the presentation of delirium. Eighteen delirious (D) and 43 delirious-demented (D-D) patients were compared on the Delirium Rating Scale (DRS), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and EEG. D-D patients had lower MMSE scores, but no differences were found in total DRS or BPRS scores or in EEG grade. DRS items were similar in the two groups except that D-D had more cognitive impairment than D. An exploratory principal components analysis of DRS items identified two core factors. The authors conclude that the presentation of delirium in the setting of concurrent dementia is very similar to delirium without dementia, with subtle differences probably attributable to dementia.

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PubMed1998

Treatment-resistant depression in late life.

Depression is the most prevalent functional psychiatric disorder in late life. It is associated with a high risk of mortality from comorbid medical illness and from suicide. Successful antidepressant treatment is one of the most effective ways to reduce disability, prevent morbidity, and improve quality of life in an older depressed patient. Treatment-resistant depression is a common clinical problem, reported to affect up to one-third of older depressed patients. However, published data on this clinically important topic are sparse. Available data and clinical experience indicate that many depressed patients labeled as "treatment resistant" or even "treatment refractory" are so labeled because of variables involving the diagnostic or treatment process, rather than because they suffer from a depression that is truly unresponsive to treatment. Unidentified comorbid medical or psychiatric conditions and misdiagnosis often contribute to treatment resistance. Atypical depressive symptoms, such as somatic and cognitive symptoms, and comorbid medical conditions that can themselves produce depressive symptoms often make it difficult to accurately assess antidepressant response in this age group. This often leads to inadequate pharmacotherapy, another major factor contributing to apparent treatment resistance. In older patients, as in younger patients, the selection of the right antidepressant, the right dose, and the right treatment duration constitute the treatment variables essential in ensuring optimal therapeutic response. Approach to treatment-resistant depression in the elderly involves reconsideration of the diagnosis and use of alternate therapeutic measures in a systematic way, including switching to another agent, combination therapy, and electroconvulsive therapy.

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PubMed1998

Behavioral disturbances of dementia.

Behavioral disturbances are common in patients with dementia. Medical intervention is needed if, for example, these behaviors threaten a patient's safety or jeopardize his or her ability to perform activities of daily living. Typical antipsychotic agents are associated with troublesome adverse effects in the elderly (e.g., anticholinergic effects, extrapyramidal symptoms). Atypical antipsychotics have reduced potential to cause these types of side effects but are not free from side effects. Recently, there has been a greater focus on the use of antidepressants to treat behavioral disturbances in dementia. Among these, selective serotonin reuptake inhibitors have been studied more commonly due to their safety profile in the elderly. Citalopram, in particular, has demonstrated efficacy in improving dementia-related behavioral symptoms.

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PubMed1997

Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report.

Neuroleptic treatment of psychotic symptoms or agitated behavior in elderly patients diagnosed with dementia is associated with reduced efficacy and increased rates of neuroleptic-induced parkinsonism in comparison to younger patients with schizophrenia. We report the first study to examine the relationship between an in vivo measure of dopaminergic function, plasma homovanillic acid (pHVA), and ratings of psychosis, agitation, and parkinsonism before and after neuroleptic treatment in dementia patients. Pretreatment pHVA was significantly correlated with parkinsonian rigidity, with a trend observed with agitation and hostility. Though mean pHVA did not change during perphenazine treatment, intraindividual change in pHVA at day 15 was correlated with improvement in hostility, with a similar trend for improvement in agitation. These preliminary findings are consistent with reports associating dopaminergic function with agitated, but not psychotic, symptoms in patients diagnosed with dementia, and with a reduced responsivity of dopaminergic systems to neuroleptic treatment in these patients.

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PubMed1997

Medical comorbidity in elderly psychiatric inpatients.

A multidisciplinary diagnostic evaluation was performed for 868 older psychiatric inpatients during a 46-month interval. A total of 402 (46%) met DSM-III-R criteria for organic mental disorders, 329 (38%) had mood disorders, 90 (10%) had psychotic disorders, and 47 (5%) had other mental disorders or conditions. Concurrent medical problems were systematically assessed and classified according to ICD-9-CM criteria. The patients suffered from a mean of 5.6 +/- 3.1 (SD) active medical problems (range 0-18). This level of medical comorbidity was significantly greater than that of older psychiatric outpatients and comparable to that of elderly inpatients in general medical hospitals. When the effects of age and education were controlled for, there were no significant differences in mean numbers of medical problems among the four groups of psychiatric inpatients. An association of major depression with diseases of the digestive system was observed and may be related to peripheral autonomic dysregulation.

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PubMed1997

The effects of perphenazine on the concentration of nortriptyline and its hydroxymetabolites in older patients.

Twenty-five older patients who presented with psychotic depression were treated with a combination of nortriptyline and perphenazine. Plasma levels of nortriptyline, E-, and Z-10-OH nortriptyline (E- and Z-10-OH-NT) were measured before and after addition of perphenazine. The mean (+/-SD) initial nortriptyline dose was 59 +/- 24 mg/day, whereas the mean final nortriptyline and perphenazine doses were 56 +/- 24 and 19 +/- 13 mg/day, respectively. The mean plasma level to dose quotient for perphenazine (0.45 +/- 0.34 nM/mg/day) was comparable to the mean quotient reported previously in older psychotic patients treated with perphenazine alone. After addition of perphenazine, the median quotient of nortriptyline plasma level to nortriptyline dose (L/D) increased significantly (from 6.1 to 8.6). This change was inversely correlated with baseline nortriptyline L/D. The median ratio of E-10-OH-NT to nortriptyline plasma level decreased significantly (from 1.6 to 1.3), whereas the median ratio of Z-10-OH-NT to nortriptyline plasma level did not change significantly. These results are consistent with the known inhibition by perphenazine of the cytochrome P450 2D6 (sparteine/debrisoquine hydroxylase), the major enzyme involved in the oxidative metabolism of nortriptyline, mostly through the formation of E-10-OH-NT. This complex alteration in the metabolism of nortriptyline induced by perphenazine emphasizes the relevance of measuring plasma levels not only of nortriptyline but also of its hydroxymetabolites in older patients who are more likely to be sensitive to their differing cardiovascular, anticholinergic, and cognitive effects.

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PubMed1997

Control-relevant intervention in the treatment of minor and major depression in a long-term care facility.

The authors assessed the effect of a control-relevant psychosocial intervention in 31 nursing home residents with either major depressive episode or minor depression. An initial group of 22 residents were randomized to either active treatment or waiting list. Four of 11 residents randomized to active treatment were deemed Responders, compared with 0 of 11 on the waiting list (P < 0.05). Of the total of 31 residents who participated in the intervention, 14 (45%) were deemed Responders during the intervention period. For these Responders, the Hamilton Rating Scale for Depression (Ham-D) and Geriatric Depression Scale scores improved significantly during the intervention. The improvement in the Ham-D was not sustained 2 months after intervention was terminated. These findings suggest that a psychosocial intervention enhancing socialization according to each resident's choice had a positive therapeutic impact on almost half of the nursing home residents with major or minor depression. However this effect could not be sustained by the residents without the support of the structured program.

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