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George S Alexopoulos

Publications and source records attributed to George S Alexopoulos.

16 recordsLinked to original sources
PubMed2003

Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life.

OBJECTIVES: To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research. PARTICIPANTS: The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy. EVIDENCE: (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates. CONSENSUS PROCESS: The Consensus Development Panel listened to presentations and participated in discussions. Workgroups considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed and edited to incorporate input from the entire Consensus Development Panel. CONCLUSIONS: Despite the availability of safe and efficacious treatments, mood disorders remain a significant health care issue for the elderly and are associated with disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization. Discriminatory coverage and reimbursement policies for mental health care are a challenge for the elderly, especially those with modest incomes, and for clinicians. Minorities are particularly underserved. Access to mental health care services for most elderly individuals is inadequate, and coordination of services is lacking. There is an immediate need for collaboration among patients, families, researchers, clinicians, governmental agencies, and third-party payers to improve diagnosis, treatment, and delivery of services for elderly persons with mood disorders.

Age Factors↗
PubMed2002

Comorbidity of late life depression: an opportunity for research on mechanisms and treatment.

Late life depression principally affects individuals with other medical and psychosocial problems, including cognitive dysfunction, disability, medical illnesses, and social isolation. The clinical associations of late life depression have guided the development of hypotheses on mechanisms predisposing, initiating, and perpetuating specific mood syndromes. Comorbidity studies have demonstrated a relationship between frontostriatal impairment and late life depression. Further research has the potential to identify dysfunctions of specific frontostriatal systems critical for antidepressant response and to lead to novel pharmacological treatments and targeted psychosocial interventions. The reciprocal interactions of depression with disability, medical illnesses, treatment adherence, and other psychosocial factors complicate the care of depressed older adults. Growing knowledge of the clinical complexity introduced by the comorbidity of late life depression can guide the development of comprehensive treatment models. Targeting the interacting clinical characteristics associated with poor outcomes has the potential to interrupt the spiral of deterioration of depressed elderly patients. Treatment models can be most effective if they focus on amelioration of depressive symptoms, but also on treatment adherence, prevention of relapse and recurrence, reduction of medical burden and disability, and improvement of the quality of life of patients and their families.

Aged↗
PubMed2002

Assessment of late life depression.

This article focuses on diagnostic and nosologic challenges intrinsic to geriatric depression, including characteristics interfering with symptom and syndrome ascertainment, the impact of medical and cognitive disorders, the usefulness of screening instruments, and barriers imposed by treatment settings. The article also identifies gaps in existing knowledge and outlines a research agenda. Nosologic characterization of depressives syndromes contributed by specific medical disorders may lead to effective strategies for prevention and treatment of depression. Studies need to examine whether treatment of depression can improve the outcome of medical illnesses requiring active patient involvement in treatment. Considering disability a distinct aspect of health status may add an important dimension to the assessment of depression and result in complementary interventions aimed at depression and disability concurrently. The provisional criteria for depression of Alzheimer's disease, if validated, may facilitate treatment research. Studies need to characterize cognitive dysfunctions associated with later development of dementia or poor treatment response in patients with depression. Care managers working together with primary care physicians can improve the recognition and treatment of depressed elderly patients by obtaining the training in using validated instruments and treatment algorithms.

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PubMed2002

Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression.

BACKGROUND: Plasma activity of dopamine beta-hydroxylase (DbetaH), the enzyme that converts dopamine to norepinephrine, is reportedly lower in patients with unipolar major depression with psychotic features (UDPF) than in those with nonpsychotic unipolar major depression (UD). Plasma DbetaH is under genetic control by the structural locus encoding DbetaH protein, DBH. This study tested the hypothesis that diagnosis-specific allelic variation at DBH accounts for lower plasma DbetaH in UDPF. METHODS: Plasma DbetaH activity was measured in samples from patients with UDPF (n = 33) and UD (n = 45). Genotypes were determined at several functional DBH polymorphisms, including C-1021T, a single nucleotide polymorphism (SNP) in the proximal 5' region that associates with variation in plasma DbetaH activity. RESULTS: Mean plasma DbetaH activity was significantly lower in UDPF than in UD. Genotyping at DBH did not reveal genetic associations distinguishing UDPF from UD. A two-way analysis of variance showed significant effects of genotype and diagnostic group but no significant interaction. CONCLUSIONS: Although the effects of the diagnosis of UDPF, and of DBH allele status, on plasma DbetaH activity were replicated, the lower plasma DbetaH in patients with UDPF was not accounted for by DBH genotype. Several explanations for this result are possible. First, other variants at DBH, or at other loci, could account for the findings. Second, nongenetic factors could account for the differences in plasma DbetaH. In this regard, we hypothesize that abnormal regulation of hypothalamic-pituitary-adrenal function in UDPF lowers expression of DbetaH protein, which could in turn alter the ratio of dopamine and norepinephrine in noradrenergic neurons, thereby promoting development of psychotic symptoms.

Adult↗
PubMed2002

Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials.

OBJECTIVES: Concerns about the safety of benzodiazepines in older adults may have led investigators and clinicians to underestimate the importance of adequately treating generalized anxiety disorder (GAD) in later life. To evaluate the safety and efficacy profile of an alternative treatment in older patients, we conducted a secondary analysis of five randomized, placebo-controlled clinical trials of extended release venlafaxine (venlafaxine ER, Effexor XR) for adult patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of GAD. DESIGN: The five multicenter, parallel-group, double-blind, prospectively randomized, placebo-controlled clinical trials used similar designs to evaluate short-term efficacy after 8 weeks. In addition, two studies evaluated efficacy and safety over 24 weeks under double-blind conditions. SETTING: Outpatients from both primary care and specialty mental healthcare settings were included. Three studies were conducted in the United States and two in Europe. PARTICIPANTS: Intention-to-treat analyses included 1,839 adult outpatients with a DSM-IV diagnosis of GAD and total scores of > or =18 on the Hamilton Rating Scale for Anxiety (HAMA). Ten percent of the patients were aged 60 and older and 5.0% were aged 65 and older. INTERVENTION: Fixed or flexible doses of venlafaxine ER in the dose range of 37.5 to 225 mg/day or matched placebo were used for 8 weeks in all studies and for 24 weeks in two studies. MEASUREMENTS: Primary efficacy variables included the HAMA total score and psychic anxiety factor, the anxiety subscale of the Hospital Anxiety and Depression (HAD) Scale, and the Clinical Global Impression of Improvement (CGI-I). Secondary efficacy variables included the HAMA somatic anxiety factor, the depression subscale of the HAD, CGI-3 severity, the Covi Scale for Anxiety, and the Raskin Scale for Depression. RESULTS: On the CGI, 66% of older patients (> or =60 years) responded to venlafaxine ER, compared with 41% for placebo (P <.01 by logistic regression). For younger patients (<60 years), comparable figures were 67% and 44%, respectively (P <.001). Analysis of variance showed no main effects for age and no age-by-treatment interactions for any of the primary or secondary efficacy outcome measures for either the 8- or 24-week analyses. Within the older adults subgroup, increasing age did not influence responses. In this cohort of GAD patients, higher levels of depression were associated with decreased responses of anxiety symptoms. In older adults, 23% of venlafaxine ER patients discontinued treatment prematurely versus 31% of those who received placebo; comparable figures for younger adult patients were 27% and 28%, respectively. Discontinuations due to adverse events were 15% versus 14% for venlafaxine ER and placebo, respectively, in older adults compared with 15% versus 8%, respectively, for younger adults. CONCLUSION: Venlafaxine ER is equally safe and well tolerated by and shows similar efficacy in younger and older patients in the treatment of GAD.

Adult↗
PubMed2002

Frontal white matter microstructure and treatment response of late-life depression: a preliminary study.

OBJECTIVE: This study tested the hypothesis that microstructural abnormalities in white matter areas of the brain containing frontostriatal tracts are associated with a low rate of remission of geriatric depression. METHOD: Thirteen older patients with major depression received open, but controlled, treatment with citalopram at a target daily dose of 40 mg for 12 weeks. Diffusion tensor imaging was used to determine fractional anisotropy in preselected white matter regions. RESULTS: Survival analysis with Cox's proportional hazards model revealed that lower fractional anisotropy of the right and the left frontal white matter regions 15 mm above the anterior commissure-posterior commissure plane was associated with a low remission rate after age was considered. Remission was not significantly associated with fractional anisotropy of lower frontal regions or a temporal region. CONCLUSIONS: Microstructural white matter abnormalities lateral to the anterior cingulate may be associated with a low rate of remission of geriatric depression.

Aged↗
PubMed2002

Executive dysfunction in geriatric depression.

OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD: The attention and executive functioning of 40 adults with major depression were compared with those of 40 healthy comparison subjects; 20 subjects were 20-60 years old, and 20 were > or =61 years. It was hypothesized that depressed subjects, regardless of age, would perform more poorly than comparison subjects on both attention and executive tasks but that the older depressed adults would evidence significantly greater impairment on executive measures. RESULTS: A significant interaction between age and depressive status was noted for tasks of executive functioning, while no age-depression interaction was found for tasks of selective or sustained attention. Older depressed adults demonstrated the slowest psychomotor speed and the poorest performance on tasks requiring set shifting, problem solving, and initiation of novel responses. CONCLUSIONS: Patients with late-life depression have significant impairment in executive functioning. These findings can guide the development of stimulated functional neuroimaging paradigms that may clarify the pathophysiology of geriatric depression. Timely identification of attentional and executive processes fundamental to the daily functioning of depressed older adults may lead to compensatory strategies that will improve the outcomes of late-life depression.

Adult↗
PubMed2002

Evidence-based practices in geriatric mental health care.

The past decade has seen dramatic growth in research on treatments for the psychiatric problems of older adults. An emerging evidence base supports the efficacy of geriatric mental health interventions. The authors provide an overview of the evidence base for clinical practice. They identified three sources of evidence-evidence-based reviews, meta-analyses, and expert consensus statements-on established and emerging interventions for the most common disorders of late life, which include depression, dementia, substance abuse, schizophrenia, and anxiety. The most extensive research support was found for the effectiveness of pharmacological and psychosocial interventions for geriatric major depression and for dementia. Less is known about the effectiveness of treatments for the other disorders, although emerging evidence is promising for selected interventions. Empirical support was also found for the effectiveness of community-based, multidisciplinary, geriatric psychiatry treatment teams. The authors discuss barriers to implementing evidence-based practices in the mental health service delivery system for older adults. They describe approaches to overcoming these barriers that are based on the findings of research on practice change and dissemination. Successful approaches to implementing change in the practices of providers emphasize moving beyond traditional models of continuing medical education to include educational techniques that actively involve the learner, as well as systems change interventions such as integrated care management, implementation toolkits, automated reminders, and decision support technologies. The anticipated growth in the population of older persons with mental disorders underscores the need for a strategy to facilitate the systematic and effective implementation of evidence-based practices in geriatric mental health care.

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PubMed2002

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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PubMedDate not supplied

Clinical presentation of the "depression-executive dysfunction syndrome" of late life.

It has been proposed that a "depression-executive dysfunction (DED) syndrome" occurs in late life. This assertion was based on clinical, neuropathological, and neuroimaging findings suggesting that frontostriatal dysfunctions contribute to the development of both depression and executive dysfunction and influence the course of depression. The authors describe the clinical presentation of DED and its relationship to disability, studying 126 elderly subjects with major depression and evaluating depressive symptoms, cognitive functioning, disability, and personality dimensions. Patients with the DED syndrome had reduced fluency, impaired visual naming, paranoia, loss of interest in activities, and psychomotor retardation, but showed a rather mild vegetative syndrome. Depressive symptomatology, and especially psychomotor retardation and loss of interest in activities, contributed to disability in DED patients, whereas paranoia was associated with disability independently of executive dysfunction. These findings may aid clinicians in identifying patients needing vigilant follow-up, because depression with executive dysfunction was found to be associated with disability, poor treatment response, relapse, and recurrence.

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PubMedDate not supplied

Provisional diagnostic criteria for depression of Alzheimer disease.

The authors, a group of investigators with extensive research and clinical experience related to both late-life depression and Alzheimer disease (AD), propose provisional affective and behavioral inclusion and exclusion diagnostic criteria for Depression of AD.

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PubMedDate not supplied

New postoperative depressive symptoms and long-term cardiac outcomes after coronary artery bypass surgery.

The authors evaluated the impact of an increase in depressive symptoms at 6 months after elective coronary artery bypass graft surgery on long-term cardiac morbidity and mortality between 6 and 36 months postoperatively. Patients who had low scores for depressive symptomatology pre-operatively and who completed follow-up at 6 months were contacted again 36 months after surgery to assess cardiac and neurologic morbidity and mortality. At 36 months after surgery, an interval history was completed, and baseline questionnaires were readministered. Follow-up was obtained on 123/124 patients (99%). The rate of combined new cardiac morbidity/mortality between 6 and 36 months was 13.6% among those with newly increased depressive symptoms at 6 months vs. 3.0% in the patients without new depressive symptoms at 6 months. Only an increase in depressive symptoms at 6 months was related to the occurrence of subsequent cardiac complications between 6 and 36 months. In this small sample of patients, increased depressive symptoms at 6 months after surgery appear to be associated with the occurrence of subsequent major cardiac morbidity/ mortality.

Aged↗
PubMedDate not supplied

Frontostriatal and limbic dysfunction in late-life depression.

Studies using diverse methods have documented frontostriatal and limbic dysfunction occurring in late-life depression. Although such impairments may result from aging-induced brain changes unrelated to depression, there are at least two reasons to suggest that they play a pathogenetic role in geriatric depression. First, frontostriatal dysfunction has been identified in at least some younger depressed subjects without known neurological abnormalities. Second, frontostriatal dysfunction may be associated with poor short- and long-term outcomes of late-life depression. Relating frontostriatal and limbic dysfunction to the course of late-life depression is an appropriate way for investigating its pathophysiological relevance, given that no biological test can be used as a validating criterion. However, this approach has experimental limitations. Studies of the course of late-life depression may be influenced by selective survival of depressed patients with favorable prognosis; factors peripherally related to the biology of depression, for example, physical handicaps; and clinical factors with unclear relationship to specific biological abnormalities, for example, personality disorders. Nonetheless, studies comparing depressed patients with control subjects complemented with studies of course of illness can bring to bear the rapidly evolving cognitive-neuroscience and brain-imaging techniques in an investigation of the networks responsible for predisposing, precipitating, and perpetuating late-life depression.

Aged↗
PubMedDate not supplied

Problem-solving therapy versus supportive therapy in geriatric major depression with executive dysfunction.

OBJECTIVE: The authors compared the efficacy of problem-solving therapy (PST) and supportive therapy (ST) in a group of elderly subjects with impairment in executive functions. This group was targeted because it has been shown to be at the risk for poor response to pharmacotherapy. METHODS: A total of 25 elderly subjects with major depression and abnormal scores in initiation/perseveration and response inhibition tasks were randomly assigned to receive weekly sessions of PST or ST for 12 weeks. The subjects were systematically evaluated by raters blind to the study hypotheses. RESULTS: PST was more effective than ST in leading to remission of depression, fewer post-treatment depressive symptoms, and less disability. A substantial part of the change in depression and disability was explained by the subjects' improvement of skills in generating alternatives and in decision-making. CONCLUSION: This preliminary study suggests that PST is effective in reducing depressive symptoms and disability in elderly patients with major depression and executive dysfunction. If these findings are confirmed, PST may become an important therapeutic alternative for a patient population who may otherwise remain symptomatic and disabled.

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