Biomedical subjects

B H Mulsant

Publications and source records attributed to B H Mulsant.

At least 19 recordsLinked to original sources

PubMed2002

Primary care physicians attitude toward diagnosis and treatment of late-life depression.

Underdiagnosis and undertreatment of late-life depression is common, especially in primary care settings. To help assess whether physicians attitude and confidence in diagnosing and managing depression serve as barriers to care, a total of 176 physicians employed in 18 primary care groups were administered surveys to assess attitudes towards diagnosis, treatment, and management of depression in elderly patients, (individuals over 65 years of age). Logistic regression was performed to assess the association of physician characteristics on attitudes. Nearly all of the physicians surveyed felt that depression in the elderly was a primary care problem, and 41% reported late-life depression as the most common problem seen in older patients. Physicians were confident in their ability to diagnose and manage depression, yet 45% had no medical education on depression in the previous three years. Physicians confidence in their ability to diagnose, treat, and manage depression, and their reported adequacy of training, do not appear to correspond to the amount of continuing medical education in depression, suggesting that physician overconfidence may potentially be serving as a barrier to care.

Journal Article↗

PubMed2002

Assessment of behavioral and psychological symptoms of dementia.

In spite of their prevalence and persistence, why are behavioral and psychological symptoms of dementia difficult for clinicians to assess and manage? This paper provides an overview of the methodological challenges encountered in measuring behavioral disturbances of dementia. Specifically, conceptual constructs of behavioral and psychological symptoms of dementia, the strengths and weaknesses of the currently existing rating instruments, analytic methodologies, and the utility of technological devices are outlined in the service of formulating future directions in behavioral and psychological symptoms of dementia assessment research.

Journal Article↗

PubMed2002

Anxiety disorders in late life: an evolving picture.

Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.

Journal Article↗

PubMed2002

The establishment of a brain bank for the study of late-life depression: a feasibility study of factors facilitating consent.

BACKGROUND: Studies of postmortem brain tissue are advancing the understanding of the pathophysiology of major depressive disorder (MDD). The nature and quality of subject samples, however, limit their applicability to late-life MDD. OBJECTIVE: To examine the feasibility of establishing a brain bank for late-life MDD, and identify clinical, demographic, and procedural factors that might facilitate subject enrollment. METHODS: Elderly subjects participating in clinical trials associated with the Mental Health Intervention Research Center for Late-Life Mood Disorders (MHIRC/LLMD) at the University of Pittsburgh were approached by clinical research staff for consent to future brain-only autopsy. Subjects who consented to participation were compared with those who refused participation on demographic and clinical variables. MHIRC/LLMD clinical research staff were interviewed to determine factors that may have facilitated or hindered the consent process and reasons for subject consent or refusal. RESULTS: Eighty out of 242 subjects (33%) subjects approached for participation in the brain bank provided consent. Consent to participate was associated with higher level of education and with lower Mini-Mental State Examination score. Several factors facilitating and hindering the consent process were identified. CONCLUSION: We provide preliminary evidence for the feasibility of establishing a brain bank for the study of late-life MDD. Future efforts may be guided by the factors identified as facilitating the consent process, especially the inclusion of family in the consent process.

Journal Article↗

PubMed2001

Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults.

BACKGROUND: Clinical studies of endogenous concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate DHEA-S in depression are limited. This study was designed to evaluate the influence of successful pharmacological treatment of late-life depression on concentrations of DHEA, DHEA-S and cortisol. METHODS: We determined endogenous concentrations of DHEA, DHEA-S and cortisol in elderly control subjects (n = 16) and in elderly depressed patients who remitted (n = 44) or failed to remit (n = 16) with pharmacological treatment. Depressed patients were treated for 12 weeks with either nortriptyline or paroxetine. RESULTS: In remitters, DHEA and DHEA-S concentrations were lower at week 12 than at week 0 (p =.002 and p =.0001, respectively). In the nonremitters and control subjects, neither DHEA nor DHEA-S concentrations changed. Decreases in hormone concentrations were associated with improvement in mood and functioning in depressed patients. Although cortisol concentrations decreased in remitters and nonremitters, the change was not significant. CONCLUSIONS: Our data suggest that the decrease in DHEA and DHEA-S in remitters is related to remission of depression rather than to a direct drug effect on steroids, as nonremitters had no change in hormone concentrations.

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PubMed2001

Dual-task performance in depressed geriatric patients.

Older patients suffering from a major depression are often impaired on tasks that require executive control processes. However, a wide variety of executive abilities exist in humans, and it is not clear that all are impaired in depression or that such impairments persist beyond remission of the depression. One executive process that plays a central role in mental operations such as working memory is the ability to co-ordinate the simultaneous performance of multiple tasks. Dual-task performance has been extensively studied in normal subjects but there is little work with depressed patients. The present study examined the performance of depressed (M age=71.0, S.D.=7.1) and control subjects (M age=69.3, S.D.=7.0) on two tasks (visual tracking and backward digit span), both when each task was carried out by itself and when the two tasks were carried out simultaneously. Dual-task performance was impaired in depressed patients prior to antidepressant treatment and this impairment persisted even after remission of the depression. These results suggest that, like other executive abilities, the ability to schedule and co-ordinate the conflicting processing demands present in a dual-task situation is impaired in depressed geriatric patients and that this impairment may be a trait effect.

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PubMed2001

Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial.

CONTEXT: Electroconvulsive therapy (ECT) is highly effective for treatment of major depression, but naturalistic studies show a high rate of relapse after discontinuation of ECT. OBJECTIVE: To determine the efficacy of continuation pharmacotherapy with nortriptyline hydrochloride or combination nortriptyline and lithium carbonate in preventing post-ECT relapse. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1998, stratified by medication resistance or presence of psychotic depression in the index episode. SETTING: Two university-based hospitals and 1 private psychiatric hospital. PATIENTS: Of 290 patients with unipolar major depression recruited through clinical referral who completed an open ECT treatment phase, 159 patients met remitter criteria; 84 remitting patients were eligible and agreed to participate in the continuation study. INTERVENTIONS: Patients were randomly assigned to receive continuation treatment for 24 weeks with placebo (n = 29), nortriptyline (target steady-state level, 75-125 ng/mL) (n = 27), or combination nortriptyline and lithium (target steady-state level, 0.5-0.9 mEq/L) (n = 28). MAIN OUTCOME MEASURE: Relapse of major depressive episode, compared among the 3 continuation groups. RESULTS: Nortriptyline-lithium combination therapy had a marked advantage in time to relapse, superior to both placebo and nortriptyline alone. Over the 24-week trial, the relapse rate for placebo was 84% (95% confidence interval [CI], 70%-99%); for nortriptyline, 60% (95% CI, 41%-79%); and for nortriptyline-lithium, 39% (95% CI, 19%-59%). All but 1 instance of relapse with nortriptyline-lithium occurred within 5 weeks of ECT termination, while relapse continued throughout treatment with placebo or nortriptyline alone. Medication-resistant patients, female patients, and those with more severe depressive symptoms following ECT had more rapid relapse. CONCLUSIONS: Our study indicates that without active treatment, virtually all remitted patients relapse within 6 months of stopping ECT. Monotherapy with nortriptyline has limited efficacy. The combination of nortriptyline and lithium is more effective, but the relapse rate is still high, particularly during the first month of continuation therapy.

Antidepressive Agents↗

PubMed2001

The 5-HTTPRS/L polymorphism and aggressive behavior in Alzheimer disease.

BACKGROUND: Aggressive behavior in Alzheimer disease (AD) has been linked to dysfunction of serotonin neurotransmission. Homozygosity for the long variant (*L) of an identified biallelic polymorphism of the serotonin transporter promoter region (5-HTTPR) is associated with increased expression of the transporter protein and increased speed of response to serotonin reuptake inhibitor treatment. OBJECTIVE: To determine whether the *L/*L genotype and the *L allele are associated with an increased risk of aggressive symptoms in patients with AD. DESIGN: Case-control study. SETTING: University hospital geriatric psychiatry inpatient program and Alzheimer disease research center. SUBJECTS: Fifty-eight patients with AD with a history of aggressive behavior and 79 never-aggressive patients with AD with comparable severity of cognitive impairment. MAIN OUTCOME MEASURES: The 5-HTTPR genotype and allele frequency. RESULTS: The *L/*L genotype was significantly associated with aggression in patients with AD (odds ratio, 2.8; 95% confidence interval, 1.2-6.5). Similar results were obtained for *L allele frequency. CONCLUSION: The 5-HTTPR*L allele and *L/*L genotype may predispose patients with AD to develop aggressive behavior.

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PubMed2001

Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly.

Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.

Adrenergic Uptake Inhibitors↗

PubMed2001

Comorbidity of depression and anxiety disorders in later life.

Since psychiatric disorders differ throughout the lifespan in phenomenology, course, and treatment, there is need for study of comorbidity of such disorders in geriatric populations. Prior findings of low prevalence of comorbid late-life anxiety disorders in depressed elderly are now disputed by recent studies. Risk factors for comorbid late-life depression and anxiety may be different from those for depression without anxiety. Similar to adults, elderly depressives with comorbid anxiety symptoms present with more severe pathology and have a more difficult course of illness, including decreased or delayed treatment response. In this paper, we review the literature on anxiety and depression comorbidity in late life, and we make recommendations for the assessment and treatment of comorbid late-life anxiety and depression. We also recommend directions for future research in the area of psychiatric comorbidity in late life.

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PubMed2001

Pharmacological treatment of depression in older primary care patients: the PROSPECT algorithm.

PROSPECT (Prevention of Suicide in Primary care Elderly-Collaborative Trial) is testing whether a trained clinician (the 'health specialist') can work in close collaboration with a primary care physician to implement a comprehensive depression management program and improve outcomes in older depressed patients. An algorithm guiding the selection and use of antidepressant medications has been developed to assist PROSPECT health specialists. This algorithm is presented and the rationale underlying the proposed treatment sequence is discussed. The PROSPECT algorithm builds upon existing guidelines after updating them and adapting them to the special circumstances of older primary care patients. Special attention has been paid to the tolerability and the target doses of the recommended antidepressant agents and to the duration of antidepressant trials. Patients who are unable to tolerate or do not respond to an antidepressant can be switched to another agent or be treated with interpersonal psychotherapy. Agents that produce only a partial response can be combined with other antidepressants or with interpersonal psychotherapy. Treatments for which empirical evidence exists are favored. However, treatments that are often poorly tolerated by elderly patients are given lower priority than treatments more likely to be tolerated. Similarly, trials that are simpler to implement in primary care are favored.

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PubMed2001

Treatment as usual (TAU) control practices in the PROSPECT Study: managing the interaction and tension between research design and ethics.

The use of treatment as usual (TAU) as a control condition may pose the considerable challenge of maintaining both scientific rigor and meeting high ethical standards in experiments on human subjects. The authors illustrate the tension and explore the relationship between research design and ethics, especially the interaction between the two, in the NIMH-funded PROSPECT study (Prevention of Suicide in Primary Care Elderly - Collaborative Trial). The goal of PROSPECT is to determine whether placement of a depression health specialist in primary care practices will have a favorable impact on rates of depression, hopelessness and suicidal ideation in elderly primary care patients with major or persistent minor depression. PROSPECT randomly assigns practices either to an intervention arm (which includes the provision of depression health specialists) or to an enhanced care arm (TAU, with the addition of screening and assessment services). TAU, enhanced by the provision of screening and assessment services, is to be used as a benchmark for measuring the effectiveness of PROSPECT's intervention. However, TAU in the epidemiological and clinical literature has also been linked to high rates of suicide in the elderly related to unrecognized and untreated or under-treated depression. The authors present their approach to managing the tension, or interaction, between the use of TAU for scientific and public health purposes and the requirement for beneficence, that is, the duty to assure the safety of human subjects in research and to do no harm. Through enhancements of TAU, by the provision of information to primary care physicians concerning the psychiatric status of their patients, the investigators attempt to meet the challenge of maintaining rigor and meeting high ethical standards.

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PubMed2001

The systematic assessment of depressed elderly primary care patients.

Studies of the primary care treatment of depressed elderly patients are constrained by limited time and space and by subject burden. Research assessments must balance these constraints with the need for obtaining clinically meaningful information. Due to the wide-ranging impact of depression, assessments should also focus on suicidality, hopelessness, substance abuse, anxiety, cognitive functioning, medical comorbidity, functional disability, social support, personality, service use and satisfaction with services. This paper describes considerations concerning the assessment selection process for primary care studies, using the PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) study as an example. Strategies are discussed for ensuring that data are complete, valid and reliable.

Activities of Daily Living↗

PubMed2001

Managing late-life depression in primary care practice: a case study of the Health Specialist's role.

Complexities in the diagnosis and treatment of late-life depression have stimulated various strategies for assisting the primary care physician to fulfil these tasks more effectively. The role of Health Specialist was developed for this purpose in a study to reduce suicidality among older depressed patients. This role includes clinical and case management tasks which aim to provide the physician with timely, patient-specific information and recommendations. Evolution of this role and its rewards/stressors during the study's first year are described.

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PubMed2001

Subjective health measures and acute treatment outcomes in geriatric depression.

BACKGROUND: Prior research suggests that elderly patients are less likely to respond to antidepressant treatment if they have low self-rated health. However, successful treatment for depression has been associated with improvement in self-rated health and other health measures. OBJECTIVES: To examine measures of self-rated health, physical disability, and social function as predictors of treatment response in late-life depression, and to assess these same health measures as treatment outcomes. We hypothesized that greater impairment in these measures would predict poorer treatment response, and that these measures would show significant improvements with recovery from depression. METHOD: Subjects were enrolled in a depression intervention study for people aged 60 and older with recurrent unipolar major depression; they were assessed with measures of self-rated health, physical disability, and social functioning at baseline and at the end of treatment. Baseline measures were compared between the 88 remitters, 11 non-remitters, and seven dropouts. Additionally, changes in the measures were examined in subjects who recovered from the index depressive episode. RESULTS: Subjects with poorer self-rated health at baseline were more likely both to drop out of treatment and to not respond to adequate treatment. This relationship was independent of demographic measures, severity of depression, physical and social functioning, medical illness, personality, hopelessness, overall medication use, and side effects or non-compliance with treatment. CONCLUSION: Although this finding is preliminary because of the small number of dropouts and non-remitters, it suggests that lower self-rated health may independently predict premature discontinuation of treatment for depression. Additionally, subjects who recovered from depression showed significant improvements in self-rated health, physical disability, and social functioning.

Activities of Daily Living↗

PubMed2001

CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression.

Recent advances in oligonucleotide microarray technology ("gene chips") permit rapid screening for DNA sequence variation. The CYP2D6 gene encodes debrisoquine hydroxylase, which metabolizes the antidepressant nortriptyline and other psychotropic medications. Nortriptyline plasma concentrations were obtained after at least three weeks of treatment in 36 geriatric patients with major depression who were taking a mean of 8.6 other medications besides nortriptyline. Oligonucleotide microarrays were used to detect 16 CYP2D6 alleles that affect debrisoquine hydroxylase activity. Subjects carrying alleles encoding impaired debrisoquine hydroxylase activity had significantly greater nortriptyline concentrations and lower nortriptyline doses than did other subjects. Significant correlations were found between the numbers of alleles encoding decreased metabolism and nortriptyline plasma concentration, nortriptyline dose, and nortriptyline plasma concentration standardized for dose, indicating a gene dosage effect. These results demonstrate that CYP2D6 genotyping on a microarray platform can be used to predict plasma antidepressant concentrations despite advanced patient age and numerous concurrent medications.

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PubMed2001

The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer disease.

BACKGROUND: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis, AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. We recently found that AD subjects homozygous for long alleles (l) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior. OBJECTIVE: To examine whether the 5-HTTPR ll genotype confers an increased risk of AD+P, and of the combined AD+P/aggressive phenotype. METHODS: The 5-HTTPR genotype was determined in 332 subjects diagnosed with possible or probable AD. All subjects received structured psychiatric assessments and were categorized with regard to their history of aggressive behaviors and psychotic symptoms. RESULTS: Consistent with other reports, AD+P was associated with a significant increased risk for aggressive behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll genotype and with an increased l allele frequency. Subjects with the combined behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll genotype and highest l allele frequency. CONCLUSION: The 5-HTTPR l allele appears to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this association in a similar behaviorally well-characterized independent sample is needed.

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PubMed2001

Influence of serotonin-transporter-linked promoter region polymorphism on platelet activation in geriatric depression.

OBJECTIVE: Depression has been associated with increased platelet activation. Variations in the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism may influence the degree of activation. The authors examined the association among depression, platelet activation, and 5-HTTLPR genotype. METHOD: Elderly subjects with (N=61) and without (N=12) major depression were assessed for cognitive impairment, cardiovascular disease, and two indices of platelet activation. The depressed subjects were genotyped for the 5-HTTLPR polymorphism. RESULTS: The depressed subjects were older, were more cognitively impaired, and had higher platelet factor 4 and beta-thromboglobulin levels; cardiovascular disease was minimal in both groups. In the depressed group, subjects with the 5-HTTLPR l/l genotype had significantly higher platelet factor 4 and beta-thromboglobulin levels. CONCLUSIONS: Platelet activation is increased in elderly depressed patients, especially those with the 5-HTTLPR l/l genotype. This finding suggests how genetic differences may influence cardiovascular mortality in depressed patients with ischemic heart disease.

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