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Benoit H Mulsant

Publications and source records attributed to Benoit H Mulsant.

At least 19 recordsLinked to original sources
PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗
PubMed2025

Multiscale dispersion entropy of resting-state EEG in older adults with Alzheimer's disease, mild cognitive impairment, and remitted major depressive disorder.

BackgroundMultiscale dispersion entropy (MDEnt) is a nonlinear EEG measure that quantifies brain complexity across time scales, reflecting both local and global brain dynamics. Previous research indicates lower complexity at short time scales in Alzheimer's disease (AD) compared to mild cognitive impairment (MCI) and healthy controls (HCs), with MCI also showing lower values than HCs. Major depressive disorder (MDD) has also been preliminarily linked to reduced complexity during acute episodes.ObjectiveTo assess whether MDEnt at short time scales can distinguish AD from MCI and HCs, and to examine complexity differences across additional groups, remitted MDD (rMDD) and rMDD + MCI, while exploring associations with cognitive performance.MethodsThe study included 316 older adults: 44 HCs, 46 with rMDD, 114 with MCI, 71 with rMDD + MCI, and 41 with AD. Resting-state, eyes-closed EEGs were analyzed using MDEnt at 24 ms (short) and 60 ms (long) time scales. Cognitive function was measured with the Montreal Cognitive Assessment and a composite cognitive score.ResultsShort time scale complexity was lowest in AD, followed by MCI, and highest in HCs; rMDD presence had no impact. Only AD showed reduced complexity at long time scales. Complexity at both time scales was significantly correlated with cognitive performance.ConclusionsThis study highlights the value of MDEnt to assess complexity at short time scale and differentiate individuals with AD, MCI, or HCs. Reduced complexity in these individuals may underlie their cognitive impairment. In contrast, our study suggests that any MDD impact on complexity is likely related to active depressive symptoms.

Humans↗
PubMed2006

Use of OSWALD for analyzing longitudinal data with informative dropout.

OSWALD (Object-oriented Software for the Analysis of Longitudinal Data) is flexible and powerful software written for S-PLUS for the analysis of longitudinal data with dropout for which there is little other software available in the public domain. The implementation of OSWALD is described through analysis of a psychiatric clinical trial that compares antidepressant effects in an elderly depressed sample and a simulation study. In the simulation study, three different dropout mechanisms: completely random dropout (CRD), random dropout (RD) and informative dropout (ID), are considered and the results from using OSWALD are compared across mechanisms. The parameter estimates for ID-simulated data show less bias with OSWALD under the ID missing data assumption than under the CRD or RD assumptions. Under an ID mechanism, OSWALD does not provide standard error estimates. We supplement OSWALD with a bootstrap procedure to derive the standard errors. This report illustrates the usage of OSWALD for analyzing longitudinal data with dropouts and how to draw appropriate conclusions based on the analytic results under different assumptions regarding the dropout mechanism.

Humans↗
PubMed2006

Statistical analysis of longitudinal psychiatric data with dropouts.

Longitudinal studies are used in psychiatric research to address outcome changes over time within and between individuals. However, because participants may drop out of a study prematurely, ignoring the nature of dropout often leads to biased inference, and in turn, wrongful conclusions. The purpose of the present paper is: (1) to review several dropout processes, corresponding inferential issues and recent methodological advances; (2) to evaluate the impact of assumptions regarding the dropout processes on inference by simulation studies and an illustrative example using psychiatric data; and (3) to provide a general strategy for practitioners to perform analyses of longitudinal data with dropouts, using software available commercially or in the public domain. The statistical methods used in this paper are maximum likelihood, multiple imputation and semi-parametric regression methods for inference, as well as Little's test and index of sensitivity to nonignorability (ISNI) for assessing statistical dropout mechanisms. We show that accounting for the nature of the dropout process influences results and that sensitivity analysis is useful in assessing the robustness of parameter estimates and related uncertainties. We conclude that recording the causes of dropouts should be an integral part of any statistical analysis with longitudinal psychiatric data, and we recommend performing a sensitivity analysis when the exact nature of the dropout process cannot be discerned.

Antidepressive Agents↗
PubMed2006

A delusion assessment scale for psychotic major depression: Reliability, validity, and utility.

BACKGROUND: Although delusions are the hallmark of major depression with psychotic features, a scale to measure the intensity of beliefs across multiple delusional domains in this condition has been unavailable. The development and assessment of the Delusional Assessment Scale (DAS) are described. METHODS: Scale items were selected initially based on previous studies of delusional ideation in schizophrenia. A three-point item to assess mood congruence was added. A 15-item scale was assessed in 92 subjects participating in the four-site collaborative study of the pharmacotherapy of major depression with psychotic features. Maximum likelihood method was used to determine scale factors. The internal consistency of these factors was determined. Comparisons between scale scores and ratings from the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) were used to assess convergent and discriminant validity. RESULTS: The data were fit by a five-factors model (impact, conviction, disorganization, bizarreness, and extension). Inter-rater reliability of the five factors ranged from .77 for conviction and .74 for impact to .37 for disorganization. Internal consistency for each of the five factors was > or =.72. Scores on specific domains were significantly correlated with the BPRS unusual thought content item and positive symptom subscale scores. CONCLUSIONS: The DAS is a reliable measure of 5 delusional domains.

Adult↗
PubMed2006

Emergence, persistence, and resolution of suicidal ideation during treatment of depression in old age.

INTRODUCTION: To determine the rate and clinical correlates of emergent, persistent, and resolved suicidal ideation during treatment of major depression in the elderly. METHODS: Based on the course of suicidal ideation before and during 12 weeks of antidepressant treatment, we classified 437 elderly patients (234 treated with paroxetine; 203 with nortriptyline) as either non-suicidal or as having "emergent", "persistent", or "resolved" suicidality. We compared the four groups on pretreatment demographic and clinical measures and with respect to depression, anxiety, and akathisia during treatment. RESULTS: Rates of emergent, persistent, and resolved suicidality were 7.8%, 12.6%, and 15.6%, respectively. Patients with persistent suicidal ideation were more likely to have recurrent depression than non-suicidal patients or patients whose suicidality resolved with treatment. At the start of treatment, patients in all three suicidal groups had lower self-esteem than non-suicidal patients. During the course of treatment, emergent suicidality was not associated with akathisia, nor did rates of emergent suicidality differ between paroxetine- and nortriptyline-treated patients. While at baseline the levels of depression and anxiety and agitation were similar in the four groups, patients with resolved suicidality had a favorable treatment response, while patients with emergent and persistent suicidality were more likely to maintain higher depression scores and had higher levels of anxiety and agitation during treatment. DISCUSSION: Emergence of suicidal ideation is not common but is clinically significant during treatment of late-life depression and may signal more difficult-to-treat-depression.

Affect↗
PubMed2006

A model of anticholinergic activity of atypical antipsychotic medications.

BACKGROUND: Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic. METHODS: We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated. RESULTS: Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied. CONCLUSIONS: Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.

Adult↗
PubMed2006

Elevation in plasma Abeta42 in geriatric depression: a pilot study.

Elevated plasma amyloid beta 1-42 (Abeta42) level has been linked to increased risk for incident AD in cognitively-intact elderly. However, plasma Abeta levels in individuals with late-life depression (LLMD), especially those with a late age of onset of first depressive episode, who are at a particularly increased risk for Alzheimer's disease, have not been studied. We compared plasma Abeta in 47 elderly with LLMD with 35 controls and examined its relationships to age of onset of first depressive episode, antidepressant treatment (paroxetine or nortriptyline), and indices of platelet activation (platelet factor 4 and beta-thromboglobulin) and brain abnormalities. Results indicated that plasma Abeta42 levels and the Abeta42/40 ratio were elevated in the LLMD group relative to controls in the overall group analyses and in the age- and gender-matched groups. MRI data indicated that higher Abeta42/40 ratio was associated with greater severity of total white matter hyperintensity burden in LLMD. Plasma Abeta levels in LLMD were not influenced by age of onset of first depressive episode or antidepressant treatment and were not related to indices of platelet activation. Our preliminary results suggest that increased plasma Abeta42 and Abeta42/40 ratio are present in geriatric depression, and future studies should be done to confirm these findings and to determine their relationship to cognitive decline and brain abnormalities associated with LLMD.

Aged↗
PubMed2006

Maintenance treatment of major depression in old age.

BACKGROUND: Elderly patients with major depression, including those having a first episode, are at high risk for recurrence of depression, disability, and death. METHODS: We tested the efficacy of maintenance paroxetine and monthly interpersonal psychotherapy in patients 70 years of age or older who had depression (55 percent of whom were having a first episode) in a 2-by-2, randomized, double-blind, placebo-controlled trial. Among patients with a response to treatment with paroxetine and psychotherapy, 116 were randomly assigned to one of four maintenance-treatment programs (either paroxetine or placebo combined with either monthly psychotherapy or clinical-management sessions) for two years or until the recurrence of major depression. Clinical-management sessions, conducted by the same nurses, social workers, and psychologists who provided psychotherapy, involved discussion of symptoms. RESULTS: Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy, 37 percent of those receiving paroxetine and clinical-management sessions, 68 percent of those receiving placebo and psychotherapy, and 58 percent of those receiving placebo and clinical-management sessions (P=0.02). After adjustment for the effect of psychotherapy, the relative risk of recurrence among those receiving placebo was 2.4 times (95 percent confidence interval, 1.4 to 4.2) that among those receiving paroxetine. The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 (95 percent confidence interval, 2.3 to 10.9). Patients with fewer and less severe coexisting medical conditions (such as hypertension or cardiac disease) received greater benefit from paroxetine (P=0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness). CONCLUSIONS: Patients 70 years of age or older with major depression who had a response to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received two years of maintenance therapy with paroxetine. Monthly maintenance psychotherapy did not prevent recurrent depression. (ClinicalTrials.gov number, NCT00178100.).

Aged↗
PubMed2006

CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly.

INTRODUCTION: The elderly are at increased risk for medication-related adverse events. Recent reports indicate that venlafaxine may put the elderly at increased risk of cardio- and cerebrovascular adverse events. We investigated the relationship between the CYP2D6 polymorphism and steady-state plasma concentration of venlafaxine (VEN) and its primary metabolite o-desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability. METHODS: Forty-six elderly participants received venlafaxine-XR for the treatment of major depression. CYP2D6 genotype and steady-state plasma levels of VEN and ODV were determined. RESULTS: Sixty-five percent of participants were homozygous of the wild type (WT) allele, whereas 35% carried one or more variant alleles associated with intermediate and poor 2D6 metabolizer status. VEN concentration per unit dose was significantly higher and ODV concentration per unit dose was significantly lower in participants who carried one or more variant alleles compared to participants who were homozygous for the WT allele. The VEN and ODV concentrations per unit dose were also correlated with creatinine clearance. CYP2D6 genotype was not associated with medication associated side-effects. CONCLUSIONS: Plasma dose-corrected concentrations of VEN and ODV correlated with genetically determined CYP2D6 enzymatic activity in depressed elders treated with venlafaxine-XR. This relationship was not masked by the effects of age-related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6-dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function.

Aged↗
PubMed2006

Preventing depression after stroke.

Mental health prevention research is an emerging and intriguing field. Preventing mental disorders is attractive as successful prevention, as it could potentially avert both emotional suffering and illness related morbidity and mortality. Several studies have looked at preventing post-stroke depression, a common complication of stroke. In this review article, we will first provide a conceptual overview of mental health prevention research. Then, we will discuss recent research supporting the prevention of depression after stroke and the likely positive effect successful prevention may have on non-psychiatric outcomes.

Depression↗
PubMed2006

Pressure ulcer prevention in black and white nursing home residents: A QI initiative of enhanced ability, incentives, and management feedback.

OBJECTIVE: To determine if educating nursing home staff about pressure ulcer prevention reduces the differential risk of pressure ulcer development in black and white nursing home residents. DESIGN: Subanalysis of a study designed to monitor the emergence of all pressure ulcers in nursing home residents during 12-week baseline and intervention periods. PARTICIPANTS: All residents and staff of a not-for-profit, 136-bed nursing home in urban western Pennsylvania. MAIN OUTCOME MEASURE: The quality improvement intervention, featuring a computer-based interactive video education program on pressure ulcer prevention and early detection, consisted of 3 components: (1) staff ability enhancement, (2) staff financial incentives, and (3) real-time management feedback. Three specific outcome measures were monitored for differential risk of pressure ulcer development in black and white nursing home residents: (1) the rate of emergent Stage I-IV pressure ulcers identified, (2) the rate of emergent Stage II-IV pressure ulcers identified, and (3) the rate of individual residents developing at least 1 pressure ulcer (Stages II-IV). RESULTS: At baseline, black residents demonstrated a higher rate of Stage II-IV pressure ulcer emergence. Black residents with any pressure ulcer were also more likely to have multiple Stage II pressure ulcers compared with white residents. During the baseline period, 31.8% of the pressure ulcers detected in white residents were Stage I, whereas no Stage I pressure ulcers were detected in black residents. During the intervention period, the rate of emergence of all pressure ulcers declined for both groups in similar trends. CONCLUSION: Black residents were more likely to have multiple Stage II-IV pressure ulcers and were less likely to have Stage I pressure ulcers identified at baseline compared with white residents. The education intervention effectively reduced the rate of pressure ulcers for all residents and eliminated the racial disparity noted during the baseline period.

Black or African American↗
PubMed2006

What is the optimal duration of a short-term antidepressant trial when treating geriatric depression?

BACKGROUND: To determine the optimal duration of an antidepressant trial in elderly patients, the authors examined the probability of eventually responding to treatment based on early improvement. METHODS: Four hundred seventy-two elderly patients with major depression (nonpsychotic, nonbipolar) were treated under protocolized conditions for up to 12 weeks and assessed weekly with the Hamilton Rating Scale for Depression. The probability of full response after 12 weeks of treatment was calculated in patients who had not fully responded after periods of treatment that lasted for 4 to 10 weeks. RESULTS: Most of the patients who had shown a partial improvement after 4 weeks of treatment became full responders after 4 or more additional weeks of treatment. By contrast, only a few of those who were nonresponders became full responders even after up to 8 additional weeks of treatment. CONCLUSIONS: After 4 weeks of treatment, it is possible to reliably identify a subgroup of elderly patients with depression who are more likely to benefit from a change in their treatment than from a few additional weeks of treatment with the same agent.

Aged↗
PubMed2006

Discrepancies in information provided to primary care physicians by patients with and without dementia: the Steel Valley Seniors Survey.

OBJECTIVE: The objective of this study was to examine associations between discrepancies in health information provided to primary care providers and severity of impairment in older patients with and without dementia. METHODS: This study included brief assessment and medical record review of 1,107 patients with a mean (standard deviation) age of 76.3 (6.6) years (range: 65-100 years) in seven small-town primary care practices. In 358 patients, detailed in-home assessment included demographics; dementia by Clinical Dementia Rating (CDR) scale; and frequencies of memory complaints, falls, and inadvertent medication nonadherence determined from medical records and standardized in-home research assessments. Main outcome variables were trends in discrepancies between chart reviews and research assessments. Main explanatory variable was CDR box total scores. RESULTS: Proportions of patients reporting memory complaints and falls, and evidence of inadvertent nonadherence, in the charts and by research assessment increased with CDR. Discrepancies between medical record and research assessment, were also associated with CDR, showing linear trends for memory complaints and inadvertent nonadherence and a quadratic trend for falls. CONCLUSION: Memory complaints, falls, and inadvertent medication nonadherence increase with dementia severity. The levels of discrepancy between information patients provided to their physicians and information they provided in response to detailed, standardized assessments, also varied with dementia severity. Physicians should be alert to the possibility of receiving unreliable health information from even mildly demented patients, whether or not dementia has been detected.

Accidental Falls↗
PubMed2006

Persistence of neuropsychologic deficits in the remitted state of late-life depression.

OBJECTIVE: Cognitive impairment in late-life depression (LLD) is prevalent, disabling, and persists despite the remission of depressive symptoms. This article characterizes neuropsychologic functioning during remission in LLD. METHODS: The authors examined longitudinal performance on a comprehensive neuropsychologic battery in 56 nondemented subjects age 60 or older who initially presented with an episode of nonpsychotic unipolar major depression and 40 nondemented, age- and education-equated comparison subjects with no history of depression. Subjects were assessed at baseline (in a depressed state) and one year later (when remitted). RESULTS: After one year, 45% of the LLD subjects were cognitively impaired despite remission of depression. Visuospatial ability, information-processing speed, and delayed memory were most frequently impaired; 94% of the patients who were impaired at baseline remained impaired one year later. Twenty-three percent of the patients who were cognitively normal while depressed developed impairment one year later. CONCLUSIONS: Most older individuals who are cognitively impaired during a depressive episode remain impaired when their depression remits. In addition, a substantial proportion of older depressed individuals who are cognitively intact when depressed are likely to be impaired one year later, although their depression has remitted.

Age Factors↗
PubMed2006

Cardiovascular changes associated with venlafaxine in the treatment of late-life depression.

BACKGROUND: Potential cardiovascular side effects from venlafaxine-XR must be considered when prescribing this medication, especially in geriatric patients, who often present with comorbid medical conditions. METHODS: Participants age 60 and older with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of a major depressive episode without psychotic features were treated openly with venlafaxine-XR for 12 weeks during which venlafaxine-XR was titrated based on tolerability and response according to predefined guidelines. Sitting and standing blood pressures and heart rates were measured. A 12-lead electrocardiogram was obtained at baseline and at week 12. RESULTS: Sixty-two participants started treatment; 59 completed at least two weeks of the 12-week study. The mean final dose of venlafaxine-XR was 195.5 mg/day (standard deviation: 72.2). Twenty-four percent (95% confidence interval [CI]: 7.3%-40.7%) of initially normotensive participants and 54% (95% CI: 34.3%-74%) of those with preexisting hypertension experienced an increase in blood pressure. Twenty-nine percent (95% CI: 14.6%-43.4%) of participants developed orthostatic hypotension. Two participants experienced a clinically significant increase in QTc interval. One participant reported new-onset mild dizziness, whereas four participants reported new-onset tachycardia or palpitation. Overall, 17 unique participants (28.8%; 95% CI: 17.3%-40.4%) experienced a new-onset cardiovascular problem, potentially related to the study medication. CONCLUSION: Overall, venlafaxine-XR was well tolerated. However, similar to previous reports, venlafaxine-XR was associated with some undesirable cardiovascular effects in some of the participants. Systematic monitoring of cardiovascular parameters during treatment with venlafaxine-XR should be strongly recommended, especially in the elderly.

Age of Onset↗
PubMed2006

Speed of improvement in sleep disturbance and anxiety compared with core mood symptoms during acute treatment of depression in old age.

OBJECTIVES: The objective of this study was to examine the relative speed of improvement in sleep disturbance and anxiety symptoms compared with core mood symptoms in acute treatment of late-life major depression. METHOD: The authors conducted secondary analysis of acute treatment data in 470 older patients treated in three federally funded studies. The authors compared rates of improvement in three Hamilton Rating Scale for Depression symptom clusters after stratification by study. RESULTS: Anxiety symptoms improved more slowly with antidepressant monotherapy and with combined pharmacotherapy/psychotherapy, whereas sleep symptoms improved at a similar rate as core mood symptoms. CONCLUSIONS: Anxiety symptoms tend to persist in patients with late-life depression.

Aged↗