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Biomedical subjects

Benoit H Mulsant

Publications and source records attributed to Benoit H Mulsant.

88 records · Page 5Linked to original sources

Identification of suicidal ideation and prevention of suicidal behaviour in the elderly.

In almost all industrialised countries, men aged 75 years and older have the highest suicide rate among all age groups. Although in younger age groups suicide attempts are often impulsive and communicative acts, suicide attempts in older people (defined as aged 65 years and older) are often long planned and involve high-lethality methods. These characteristics, in addition to the fact that elderly are more fragile and frequently live alone, more often lead to fatal outcome. In later life, in both sexes, the most common diagnosis in those who attempt or complete suicide is major depression. In contrast to other age groups, comorbidity with substance abuse and personality disorders is less frequent. Physical illness plays an important role in the suicidal behaviour of the elderly: most frequently, depression and illness co-occur; less often, the physical illness or the treating medications are causally related to the depressive symptoms. However, only 2 to 4% of terminally ill elderly commit suicide. In addition to physical illness, complicated or traumatic grief, anxiety, unremitting hopelessness after recovery from a depressive episode and history of previous suicide attempts are risk factors for suicide attempts and completed suicide. During a depressive episode, elderly patients with suicidal ideation have higher levels of anxiety and, during treatment, anxiety decreases the probability of remission and recovery. As well as overt suicide attempts, indirect self-destructive behaviours, which often lead to premature death, are common, especially in residents of nursing homes, where more immediate means to commit suicide are restricted. Although we do not have randomised trials of treatment, studies suggest that antidepressant treatment may decrease suicide risk. Prevention and treatment trials are underway to detect the effectiveness of improved treatment of depression by primary care physicians as a means of reducing the prevalence of depressive symptoms, hopelessness and suicidal ideation.

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Anxiety symptoms in elderly patients with depression: what is the best approach to treatment?

Depressed elderly persons frequently have concurrent symptoms of anxiety or comorbid anxiety disorders. Such comorbidity is associated with a more severe presentation of depressive illness, including greater suicidality. Additionally, most antidepressant treatment studies in the elderly have found poorer treatment outcomes in those with comorbid anxiety (including delayed or diminished response and increased likelihood of dropout from treatment). While antidepressants such as selective serotonin reuptake inhibitors and tricyclic agents are efficacious for late-life depression, there is no evidence that either class is superior, in terms of efficacy or tolerability, in the treatment of anxious depression. Rather, the amount and quality of clinical management, and not the particular medication chosen, appears to influence the likelihood of remission or treatment withdrawal in anxious depressed elderly patients. Co-prescription of benzodiazepines, typically lorazepam, is also warranted in some cases for severe anxiety or insomnia, but carries the risk of cognitive or motor impairment. It is our experience that close clinical monitoring, together with maximization of antidepressant treatment (by maximising dosage, augmenting or switching agents in cases of partial or no response, and/or adding psychotherapy) will almost always result in remission of depressive symptoms, together with improvement of anxiety, in these individuals. Therefore, optimism should be maintained when treating the depressed elderly individual, even when comorbid anxiety is present.

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Clinically relevant behaviors in elderly hip fracture inpatients.

OBJECTIVE: To examine the range of behaviors documented by inpatient rehabilitation staff and the association of these behaviors with functional outcome, in elderly persons undergoing rehabilitation after hip fracture. METHOD: Subjects were 137 patients, aged 60 and older, admitted to a rehabilitation hospital after a hip fracture, defined as having either a good or poor rehabilitation outcome based on change in Functional Independence Measure motor subscale scores during the course of their admission. Their charts were systematically reviewed for nursing and therapy staff documentation of behaviors. Prevalence of behaviors was compared between good and poor rehabilitation outcome group. RESULTS: Disturbances in cognition and rehabilitation participation were common and were associated with poorer rehabilitation outcome. Behaviors reflective of depression and anxiety were relatively uncommon and not associated with rehabilitation outcome. CONCLUSION: Rehabilitation staff frequently detect and document disturbances in cognition and participation that are associated with poorer rehabilitation outcome. It is recommended that staff observations be routinely added to mental health evaluations. Additionally, routine mental health screening and required staff documentation of behaviors would improve case detection rate.

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Risk factors for falls during treatment of late-life depression.

BACKGROUND: Prior studies have found that antidepressant medications are associated with an increased risk of falling in elderly persons. However, little is known about the prevention of falls during treatment for depression in elderly persons. This study evaluated the time course and potential risk factors for falls in a treatment protocol for late-life depression to identify specific at-risk periods and risk factors for falls in this population. METHOD: One hundred four subjects aged 69 years and over were treated in a protocolized manner using paroxetine and interpersonal psychotherapy. Those who did not respond received augmentation therapy with bupropion, nortriptyline, or lithium. Subjects were assessed at baseline and weekly during treatment; demographic and clinical characteristics of those who experienced a fall during treatment were compared with those who did not fall. Cox proportional hazards models were used to define risk factors for falls in univariate and multivariate models. RESULTS: During a mean of 21 weeks of treatment, 40 subjects (38%) fell. About half (53%) of the subjects fell during the first 6 weeks of treatment. In the multivariate model, memory impairment and orthostatic changes in blood pressure during treatment were risk factors for falling. Additionally, augmentation with bupropion appeared to be a risk factor for falls in univariate analysis, but this result is preliminary due to the small number of subjects who took bupropion. CONCLUSION: Increased monitoring for falls is warranted during the acute treatment of late-life depression. When treating such patients, clinicians should be especially watchful of those with memory impairments or those who develop orthostatic blood pressure changes; orthostatic blood pressure should be measured throughout acute treatment. Additionally, augmenting paroxetine with bupropion may also increase the risk of falls, and this medication combination should be used with caution in elderly patients.

Accidental Falls↗

A randomized comparison of high-charge right unilateral electroconvulsive therapy and bilateral electroconvulsive therapy in older depressed patients who failed to respond to 5 to 8 moderate-charge right unilateral treatments.

BACKGROUND: Electroconvulsive therapy (ECT) is the treatment of choice in some older patients with severe depression. When compared with younger depressed patients, older patients have been shown to be as likely to respond to ECT but more likely to develop cognitive impairment. This study addresses whether adults aged 50 years and over who have already failed to respond to at least 5 moderate-charge right unilateral (RUL) ECT treatments (150% above seizure threshold) are more likely to benefit from a switch to high-charge RUL ECT (450% above threshold) or to bilateral (BL) ECT. METHOD: Twenty-four patients who were treated with 5 to 8 moderate-charge RUL ECT treatments and who failed to improve sufficiently were randomly assigned to receive either BL ECT (N = 11) or high-charge RUL ECT (N = 13). Depressive (24-item Hamilton Rating Scale for Depression) and cognitive scores (Mini-Mental State Examination [MMSE]) were compared under double-blind conditions at 3 phases of treatment. RESULTS: Patients in the BL ECT group exhibited significantly greater cognitive impairment (mean MMSE score decrease of 1.13) than those receiving high-charge RUL ECT (mean MMSE increase of 1.71). There were no statistically significant differences in clinical response to BL or high-charge RUL ECT (63.6% and 61.5%, respectively) or in depressive symptom remission (18.1% and 46.2%). CONCLUSION: These results suggest that older patients who fail to respond to moderate-charge RUL ECT may benefit from a switch to high-charge RUL ECT rather than BL ECT. Larger future studies will be needed to compare clinical response in patients switched from moderate-dose RUL ECT to higher-dose RUL or to BL ECT.

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Intent-to-treat analysis for clinical trials: use of data collected after termination of treatment protocol.

Following patients for a period of time after termination of treatment protocols is a common practice in clinical trials of drug treatments. After termination of the protocol treatment, patients are usually provided with medical care as deemed appropriate, e.g. different doses of the same drug, augmentation with other drugs, or different drugs. Data collected on patients when they are not in the treatment protocol are termed "off-treatment" data to be differentiated from "on-treatment" data that are collected while patients are in the treatment protocol. The purpose of the present paper is to describe some recent statistical methodological advances in the use of "off-treatment" data for intent-to-treat (IT) analysis using mixture models [Biometrics 52 (1996) 1002]. Two-piece spline models conditional on the protocol treatment dropout time are developed first. The two pieces of the spline model represent the on-treatment and off-treatment segments of data and are joined at the dropout time. The weighted average of the two-piece conditional models across realizations of the dropout times provides the mixture model for the pragmatic IT analysis. The weights are the estimates of the probabilities of the dropout times. The mixture model is amenable to an explanatory analysis which assumes that the patients remain on their assigned treatments. The model allows the parameters of the splines to depend on the dropout time. Statistical inference is based on bootstrap sampling procedures. We have illustrated this methodology using data from a drug trial comparing nortriptyline and paroxetine in the treatment of major depression in older patients.

Clinical Trials as Topic↗

Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine.

Cognitive dysfunction is common in older persons suffering from a major depression. However, the degree to which this dysfunction is reversible with successful treatment of the depression remains uncertain. The present study examined the effects that treatment (randomized double-blind design) with either an SSRI (paroxetine) or a tricyclic antidepressant (nortriptyline) had on cognition in older depressed patients. The patients' performance was compared to that of a group of normal controls of similar age and education. Patients and controls were administered measures of working memory, information-processing speed, episodic memory and attention five times over the course of a 12 week trial. At baseline, the patients performed more poorly than the elderly controls on all cognitive measures. While the patients' performance did improve over the course of their treatment, the magnitude of this improvement did not exceed that produced in the elderly controls by practice alone. The same pattern of results was evident in both intent-to-treat and responder analyses. Thus, there was no evidence that the depressed patients' cognitive performance normalized after response to antidepressant therapy. Neither the patients' age at onset nor their baseline level of cognitive functioning influenced the amount by which their performance improved over the 12 week trial. There was no difference between paroxetine and nortriptyline in the amount of cognitive change associated with treatment. The present results suggest that cognitive dysfunction persists in older depressed patients even after their mood disorder has responded to antidepressant medications.

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Mental health training for nursing home staff using computer-based interactive video: a 6-month randomized trial.

OBJECTIVE: Mental health education for the staffs of nursing homes is difficult to provide and often inadequate. The objectives of this study were to design and assess a curriculum of staff training on depression and dementia that is accessible, educational, and relevant. DESIGN: A core curriculum of 12 computer-based interactive video training modules was created in a television news-documentary format to educate nursing home staffs. A randomized trial of the first six modules, which are dedicated to mental health and aging, was conducted at a computer site (CS), a "lecture site" (LS), and control site (CON). SETTING: Three not-for-profit nursing facilities in Western Pennsylvania. PARTICIPANTS: The certified nursing assistants, and other nursing staff participated in the study as part of their required training. INTERVENTION: Nursing staffs at the two intervention sites (CS and LS) were mandated to participate in monthly educational sessions. At the CS, the computer program scheduled staff members each month for 45 minutes of individual, self-paced training using the interactive video modules. At the LS, staff members were scheduled to attend a 45-minute monthly lecture with identical learning objectives delivered by an advanced degree nurse educator. A videotape of the lectures was shown at two additionally scheduled times during the month to accommodate all shifts. MEASUREMENTS: Compliance and satisfaction with training were monitored at both intervention sites. Knowledge was assessed at the CS, LS, and CON, before each monthly training session, and with a cumulative post-training exam, administered at the end of the 6-month study. RESULTS: Over the 6-month period, training compliance was 66% and 22% at CS and LS, respectively (P < 0.001). Satisfaction with training and the relevance of training were rated significantly higher at the CS (P < 0.0001). Before the study, assessed knowledge was similar at the CS, LS, and CON. After 6 months, the CS scored significantly higher than the LS and CON in terms of knowledge (P < 0.005). CONCLUSION: Individual, self-paced, interactive video education for nursing home staff resulted in greater compliance and satisfaction with training compared to staff receiving lectures. Knowledge of core concepts was greater for staff of the computer site compared to the staffs of either the lecture or control sites at the end of this 6-month study.

Clinical Trial↗

Educating the families of nursing home residents: a pilot study using a computer-based system.

OBJECTIVES: To enhance family participation in nursing home care through a Web-based system of interactive video training and interactive communication with the facilities. DESIGN: In this pilot study, focus groups guided the design and development of a prototype computer system for family members of nursing home residents. Its usability and functionality was tested with family members of diverse age and ethnicity. SETTING: Nursing home sites around Pittsburgh, Pennsylvania. PARTICIPANTS: The study comprised 18 family members who were primary decision makers for nursing home residents. Most were elderly females, and 33% were African-Americans. INTERVENTION: Computer-based education on dementia, agitation/aggression, and caregiver strategies. MEASUREMENTS: Knowledge was assessed with a 16 question pretest and posttest. Satisfaction surveys were completed. RESULTS: Knowledge of key principles of dementia care improved significantly (paired t test, t = 5.9(17), P < 0.0001). User satisfaction and "ease of use" received high ratings. CONCLUSION: Computer-based interactive videos can be used to educate family members of nursing home residents on dementia care. A complete curriculum of education and interactive bulletin boards for family inclusion in care planning are currently under development and will be tested to determine any impact on resident quality of life and quality of care outcomes.

Adult↗

Pharmacotherapy of bipolar disorder in old age: review and recommendations.

The authors reviewed the evidence-base for pharmacological treatment of mania and bipolar (BP) depression in late life. Treatment benefits and side effects may be modified by age-associated factors, such as neurocognitive impairments. Lithium and divalproex have most often been studied in elderly patients, and both may be efficacious in acute treatment of mania, but there are no controlled efficacy or effectiveness trials. The role of atypical antipsychotic agents remains to be clarified. Similarly, there are no systematic studies of the treatment of BP depression in elderly patients. The authors make suggestions for management and delineate priorities for research.

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Executive functioning, illness course, and relapse/recurrence in continuation and maintenance treatment of late-life depression: is there a relationship?

OBJECTIVE: The authors tested the hypothesis that impaired executive functioning leads to high rates of relapse and recurrence in late-life depression. METHODS: They analyzed data from subjects participating in two independent intervention trials. Study I included 53 elderly depressed patients who participated in an open trial comparing the efficacy of paroxetine and nortriptyline and recurrence prevention over 18 months. Study II focused on 146 elderly depressed patients who received open treatment with paroxetine in a relapse-prevention study over 4 months of continuation treatment. They examined the effect of cognitive functioning, in general, and executive functioning, in particular, on time-to-relapse/recurrence, using baseline and post-treatment measures of neuropsychological functioning. RESULTS: The associations between cognitive measures and both probability of, and time-to-relapse/recurrence were small and statistically nonsignificant. CONCLUSION: Data failed to support the hypothesis that cognitive impairment, in general, or executive dysfunction, in particular, predicts relapse or recurrence of major depression in late life. Authors recommend future testing of the hypothesis with detailed, comprehensive measures over longer periods of observation during maintenance trials.

Age of Onset↗

Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementia.

Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B12 serum levels and cognitive and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty-seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects with low B12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.

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Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression.

OBJECTIVE: The variable speed and durability of response to antidepressant medications in geriatric depression is a significant clinical problem. The authors evaluated changes in cerebral glucose metabolism measured with positron emission tomography (PET) during a clinical trial designed to accelerate medication response by the use of one night of total sleep deprivation (TSD), and they asked whether changes would correlate with treatment outcome after 12 weeks of antidepressant treatment. METHODS: Twelve elderly, unipolar depressed patients underwent serial PET studies at baseline, post-TSD, post-recovery sleep (after an initial paroxetine dose), and after 2 weeks of paroxetine treatment. RESULTS: Decreased regional glucose metabolism after TSD, recovery sleep, and 2 weeks of treatment was associated with clinical improvement at 12 weeks. The right cingulate gyrus area was consistently correlated with clinical improvement across treatment conditions. CONCLUSION: These data indicate that the early metabolic alterations in the right cingulate gyrus and the persistence of these adaptive changes are associated with improvement in depressive symptoms.

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Response speed and rate of remission in primary and specialty care of elderly patients with depression.

OBJECTIVE: Depression treatment in primary care elderly patients has been inadequate, resulting in low rates of response and remission. The authors compared treatment remission rates and time-to-remission of elderly subjects enrolled in two ongoing depression treatment studies, one in primary care practices ("PROSPECT") and the other in an academic tertiary mental health care center ("MTLD-2"), in order to assess the value of standardizing and intensifying depression treatment in primary care elderly patients. METHODS: Authors compared remission rates and time to criterion endpoints via survival analysis. The 126 PROSPECT subjects (mean age 71) included primary care patients with either current episodes of major depression or minor depression. The 129 MTLD-2 subjects (mean age 77) had single or recurrent unipolar major depression. PROSPECT subjects received a variety of open treatments, including the drug citalopram and/or interpersonal psychotherapy (IPT). Both patient and provider preferences influenced treatment selected. MTLD-2 subjects received more structured, open paroxetine treatment and IPT. RESULTS: The remission rates of PROSPECT and MTLD-2 were 86.5% and 88.4%, respectively. Median time-to-remission in PROSPECT was significantly longer than in MTLD-2 (12 weeks versus 8.7 weeks). Limiting the survival analysis to subjects with major depression produced faster attainment of remission criteria. CONCLUSION: Notwithstanding these differences in speed and rate of symptom resolution, good treatment can work well in geriatric depression in the primary care sector.

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Verification of scale sub-domains in elderly patients with dementia: a confirmatory factor-analytic approach.

OBJECTIVE: Use of cognitive, psychiatric and behavioral domains to assess the effectiveness of a pharmacological or behavioral intervention in the treatment of neurodegenerative disorders (e.g., Alzheimer disease) aids the identification of specific types of impairment or distress in behavioral status and quality-of-life issues in this population. With confirmatory approaches to subscale development readily available, we can obtain a more precise understanding of the sub-components of a scale, potentially providing the basis for selecting behavioral and/or quality-of-life outcome measures that may be more sensitive to the effects of pharmacological or behavioral interventions. METHODS: The authors illustrate the use of a confirmatory factor-analytic approach to verify scale sub-domains of the Neurobehavioral Rating Scale (NBRS) in elderly patients with dementia. With data collected from two groups of patients being treated for significant psychiatric and behavioral symptoms, authors investigated the relationships among scale items in order to test several competing models, including a general one-factor model, a first-order multifactor model, and a second-order factor model. RESULTS: The first-order model, with seven factors, provided the best fit to the correlations among items in the NBRS, indicating the multidimensionality of problematic behaviors and symptoms exhibited by dementia patients. CONCLUSION: Authors advocate the use of a confirmatory factor-analytic approach to verify scale sub-domains in other, more widely used rating scales for patients with dementia.

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