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Biomedical subjects

Benoit H Mulsant

Publications and source records attributed to Benoit H Mulsant.

At least 37 records · Page 2Linked to original sources
PubMed2006

Impact of prior treatment exposure on response to antidepressant treatment in late life.

OBJECTIVE: The objective of this study was to describe the correlates of prior antidepressant exposure and its association with response to protocolized treatment in older patients with major depression. METHODS: Based on their prior antidepressant treatment exposure, 193 elderly patients with a major depressive episode were divided into three groups: those with no prior treatment for their current episode (not treated [TN]), those with antidepressant trials of inadequate dose or duration ("treatment-inadequate" [TI]), and those with at least one adequate trial but persisting depression ("treatment-resistant" [TR]). All patients then received protocolized treatment with interpersonal psychotherapy (IPT) and paroxetine plus pharmacologic augmentation if needed. The demographic, clinical, and outcome information were compared among these three groups. RESULTS: Approximately one-third of the patients referred to the study had been adequately treated (TR), one-third had been inadequately treated (TI), and one-third were not treated for the current episode (TN). Treatment completion rates and reasons for dropping out did not differ statistically among TR, TI, and TN patients. TR patients took longer to respond (13.0 weeks) than either TI or TN patients (7.6 and 8.0 weeks, respectively). TR and TI patients had lower response rates (67% and 71%) than TN patients (86%). CONCLUSIONS: Prior treatment exposure is an important correlate of course and outcome in late-life depression. Most TR and TI patients eventually respond, but TR patients may require more intensive and longer courses of treatment than TI and TN patients.

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PubMed2006

Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment.

BACKGROUND: Anxiety disorders are common in later life, but little is known about the long-term benefits and risks of pharmacotherapy. METHOD: 30 patients aged 60 years and older, with a DSM-IV anxiety disorder, entered a 32-week trial of citalopram. Data gathered at baseline and follow-up included anxiety symptoms using Hamilton Rating Scale for Anxiety (HAM-A) scores, quality of life using the Medical Outcomes Study 36-item Short Form (SF-36), and sleep using the Pittsburgh Sleep Quality Index (PSQI). Data analysis consisted of mixed-effect repeated measures models of HAM-A scores and pre-post comparison of SF-36 and PSQI scores. RESULTS: 30 persons entered treatment; most (27/30) had a primary DSM-IV diagnosis of generalized anxiety disorder (2 had panic disorder; 1 had posttraumatic stress disorder). Three subjects discontinued study medication due to side effects, 5 were terminated because of nonresponse, and 5 dropped out of the study for other reasons; thus, 17 subjects (57%) completed 32 weeks of treatment. Subjects' HAM-A scores improved significantly, with continuing improvements up until about 20 weeks of treatment. On the basis of a criterion of reduction in HAM-A to < 10 during the trial, 60% (18/30) of subjects were responders. Those who completed the 32-week trial had significant improvements in sleep and quality of life-including social functioning, vitality, mental health, and role difficulties due to emotional problems. CONCLUSIONS: In this 32-week study of citalopram for elderly persons with anxiety disorders, 60% responded. Those who received a full course of treatment experience significant improvements in quality of life and sleep quality.

Age Factors↗
PubMed2005

Ability, incentives, and management feedback: organizational change to reduce pressure ulcers in a nursing home.

OBJECTIVE: Quality improvement (QI) processes in nursing homes are highly variable and often ineffective. This study evaluated an innovative QI process to reduce pressure ulcers (PUs) in a nursing home with a high rate of PUs. DESIGN: This was a 48-week, longitudinal study comparing the incidence of PUs during 12-week baseline and intervention and post-intervention periods. SETTING: Not-for-profit, 136-bed nursing home in urban Western Pennsylvania. PATIENTS OR OTHER PARTICIPANTS: All residents and all staff at the nursing home participated in this study. INTERVENTIONS: The intervention consisted of 3 components: Ability enhancement, incentivization, and management feedback. To enhance ability, all staff members completed a computer-based interactive video education program on PU prevention and were mandated to use penlights to promote early detection. Incentivization included $75 for each staff member if the desired reduction in PU incidence was achieved. Management feedback provided real-time information of staff"s adherence to the mandated training. MAIN OUTCOME MEASURES: Outcome measures consisted of staff's adherence to mandated training and the incidence of new PUs during the baseline period compared to the intervention and post-intervention periods. RESULTS: Management responded to noncompliance with training with both rewards and stepped discipline. Adherence to protocol, as measured by training compliance, was 100%. There was a significant reduction (P < .05) in the incidence of stage 2 or worse PUs during the intervention period. During the post-intervention periods, the effect was lost. CONCLUSION: An innovative QI initiative resulted in a significant decrease in PUs in 1 facility. This intervention was not sustainable when the 3 components of the QI intervention were no longer actively maintained.

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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.

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PubMed2005

Somatic symptoms of depression in elderly patients with medical comorbidities.

OBJECTIVE: Somatic symptoms of depression such as fatigue create a diagnostic dilemma when assessing an older patient with medical comorbidities, since chronic medical illnesses may produce similar symptoms. Alternatively, somatic symptoms attributed to medical illness may actually be caused by depression. These analyses were designed to determine if somatic symptoms in older patients are more strongly associated with chronic physical problems or with depression. DESIGN: Reanalysis of data from an observational study of depression in primary care and a randomized trial of paroxetine and nortriptyline for the treatment of major depression. Patients were evaluated with a structured diagnostic interview and a battery of psychiatric, physical, and psychosocial measures. PARTICIPANTS: Two hundred and forty eight primary care and psychiatric patients aged >or= 60 years. METHODS: Associations among depression, somatization, and chronic physical problems were examined using correlations and regression modeling. RESULTS: Two somatization measures, the Asberg Side Effects Rating Scale and the Utvalg for Kliniske Undersogelser (UKU), were significantly associated with psychological symptoms of depression (r = 0.73 and r = 0.76, p < 0.0001) but not with medical comorbidities (r = 0.02, p = 0.16 and r = 0.10, p = 0.78). In multiple regression models, psychological symptoms of depression remained significant predictors of somatization (p < 0.0001) after controlling for age, gender, and medical comorbidities. CONCLUSIONS: In older patients with medical disorders and multiple somatic complaints, clinicians should consider the possibility of depression. Rating scales emphasizing somatic symptoms associated with depression may provide a more accurate measure of depression severity than those excluding such symptoms.

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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.

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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

Generalized anxiety disorder in late life: lifetime course and comorbidity with major depressive disorder.

OBJECTIVE: Generalized anxiety disorder (GAD) in elderly persons is highly prevalent, but little is known about its course, age at onset, and relationship to comorbid major depressive disorder (MDD). The authors assessed the course and comorbidity of late-life GAD and MDD. METHODS: Authors assessed elderly subjects in anxiety or depression intervention studies who had a lifetime history of GAD, with current MDD (N=57) or without (N=46). Subjects' lifetime course of illness was charted retrospectively. RESULTS: The 103 subjects had a mean age of 74.1 years, and a mean age at onset of GAD of 48.8 years; 46% were late-onset. GAD episodes were chronic, and 36% were longer than 10 years. Of the comorbid GAD-MDD patients, most had different times of onset and/or offset of the disorders; typically, GAD preceded MDD. CONCLUSIONS: Elderly subjects with GAD tended to have chronic symptoms lasting years-to-decades, without interruption, and many have late onset. Elderly persons with lifetime GAD and MDD tend to have different onset and offset of the two disorders. Findings characterize late-life GAD as a chronic disorder distinct from MDD.

Age of Onset↗
PubMed2005

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.

Activities of Daily Living↗
PubMed2005

A pilot study of standardized treatment in geriatric bipolar disorder.

OBJECTIVE: The authors sought to determine the feasibility of treating elderly adults with bipolar disorder under standardized-treatment conditions. METHODS: Thirty-one patients age 60 and older with bipolar disorder were treated in standardized pathways. Mood state was checked at each study visit with the Hamilton Rating Scale for Depression-17 item (Ham-D-17) and the Young Mania Rating Scale (YMRS). RESULTS: Defining "well days" as both Ham-D and YMRS scores of <or=10, the mean percentage of well days was 72.5 (range: 0%-100%) over study participation. CONCLUSIONS: Treating older adults with bipolar disorder under standardized treatment is feasible and is associated with low symptom levels. However, most older adults with bipolar disorder do not experience sustained recovery.

Adolescent↗
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.

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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.

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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

Remission in depressed geriatric primary care patients: a report from the PROSPECT study.

OBJECTIVE: This study compared time to first remission for elderly depressed patients in primary care for practices that implemented a care management model versus those providing usual care. In addition, it sought to identify risk factors for nonremission that could guide treatment planning and referral to care managers or specialists. METHOD: Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) data were analyzed. Participants were older patients (> or =60 years) selected following screening of 9,072 randomly identified primary care patients. The present analysis examined patients with major depression and a 24-item Hamilton Depression Rating Scale score of 18 or greater who were followed for at least 4 months (N=215). Primary care practices were randomly assigned to offer the PROSPECT intervention or usual care. The intervention consisted of services of trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 18 months. RESULTS: First remission occurred earlier and was more common among patients receiving the intervention than among those receiving usual care. For all patients, limitations in physical and emotional functions predicted poor remission rate. Patients experiencing hopelessness were more likely to achieve remission if treated in intervention practices. Similarly, the intervention was more effective in patients with low baseline anxiety. CONCLUSIONS: Longitudinal assessment of depression, hopelessness, anxiety, and physical and emotional functional limitations in depressed older primary care patients is critical. Patients with prominent symptoms or impairment in these areas may be candidates for care management or mental health care, since they are at risk for remaining depressed and disabled.

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PubMed2005

Predictors of adequacy of depression management in the primary care setting.

OBJECTIVES: Depression is most commonly treated in the primary care setting. However, most studies have shown that depression care in this setting is often inadequate. This study examined the adequacy of antidepressant treatment and overall depression management by primary care physicians and identified patient characteristics related to inadequate care. METHODS: Adequacy of depression care among patients with depression who presented to a primary care office was evaluated by using physicians' self-reports and medication prescription data. Adequacy of depression care was measured in two ways: adequacy of the current medication trial was measured by using the Antidepressant Treatment and History Form (ATHF), and adequacy of overall management by the physician was measured by using an algorithm developed for this study. The association was examined between patient characteristics and adequacy of the medication trial or depression management. RESULTS: Data were gathered for 389 patients with depression. Overall, 71 percent of patients had adequate ATHF scores, and 75 percent were judged to receive adequate depression management. No significant differences in adequacy were seen on the basis of race, age, or gender. When depressive symptoms were almost absent or extremely severe, 91 percent of patients were adequately managed; in contrast, when symptoms were mild, mild to moderate, or moderate 69 percent of patients were adequately managed. Additionally, specific medications, such as sertraline and fluoxetine, were associated with a lower likelihood of an adequate ATHF score. CONCLUSIONS: A majority of these primary care patients were adequately treated for depression, with no detectable disparity related to race or age. However, mild to moderate depressive symptoms (as opposed to remitted or severe symptoms) and specific medications were associated with a lower rate of adequacy. These findings have implications for ways that primary care physicians could be trained to more adequately manage the spectrum of severity of depression.

Adult↗