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Biomedical subjects

G S Alexopoulos

Publications and source records attributed to G S Alexopoulos.

At least 37 records · Page 2Linked to original sources

The expert consensus guideline series. Pharmacotherapy of depressive disorders in older patients.

OBJECTIVES: Depression in older patients contributes to personal suffering and family disruption and increases disability, medical morbidity, mortality, suicide risk, and healthcare utilization. The majority of clinical trials of antidepressant treatments are conducted in younger patients. For this reason, clinicians often have to extrapolate from studies in populations that do not present the same problems as older patients. For example, older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment. Older patients as a rule need to be on many medications, some of which may contribute to depression and/or interact with antidepressants. Finally, older adults metabolize medications slowly and are more sensitive to side effects than younger patients. Because of these complexities, we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature. METHOD: After reviewing the literature and convening a work group of experts, we prepared a written survey with 64 questions that asked about 857 options. 618 of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For the other options, the experts were asked to write in answers (e.g., average doses) or to check a box to indicate their preferred answer. We sent the survey to 50 national experts on geriatric depression, all of whom completed it. Consensus on each option was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 89% of the options rated on the 9-point scale. The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment. For unipolar nonpsychotic major depression, the preferred strategy is an antidepressant (selective serotonin reuptake inhibitor [SSRI] or venlafaxine XR preferred) plus psychotherapy. For unipolar psychotic major depression, the treatment of choice is an antidepressant (SSRI or venlafaxine XR) plus one of the newer atypical antipsychotics. Electroconvulsive therapy is also first line. For dysthymic disorder or persistent milder depression, the experts recommend combining an antidepressant (SSRIs preferred) and psychotherapy. If the patient has a comorbid medical condition (e.g., hypothyroidism) that is contributing to the depression, the experts recommend treating both the depression and the medical condition from the outset. The SSRIs were the top-rated antidepressants for all types of depression. Among them, the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline. Paroxetine was another first-line option, and fluoxetine was rated high second line. The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy, supportive psychotherapy, problem-solving psychotherapy, and interpersonal psychotherapy. The experts also give strong support to including appropriate psychosocial interventions (e.g., psychoeducation, family counseling, visiting nurse services) in the treatment program. The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression, for 1-3 years for a patient who has had 2 such episodes, and for longer than 3 years if there is a history of 3 or more episodes. CONCLUSIONS: The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for addressing common clinical dilemmas in older individuals. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions. Nonetheless, the guidelines cannot address the complexities involved in the care of each individual patient and can be most helpful in the hands of experienced clinicians.

Aged↗

Executive dysfunction and long-term outcomes of geriatric depression.

BACKGROUND: This study investigated the relationship of executive and memory impairment to relapse, recurrence, and course of residual depressive symptoms and signs after remission of geriatric major depression. METHODS: Fifty-eight elderly subjects remitted from major depression received continuation nortriptyline treatment (plasma levels 60-150 ng/mL) for 16 weeks and then were randomly assigned to either nortriptyline maintenance therapy or placebo for up to 2 years. Diagnosis was made using the Research Diagnostic Criteria and the DSM-IV criteria after an interview using the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction and memory were assessed with the Dementia Rating Scale, disability and social support were rated with the Philadelphia Multiphasic Instrument, and medical burden was assessed with the Cumulative Illness Rating Scale. RESULTS: Abnormal initiation and perseveration scores, but not memory impairment, were associated with relapse and recurrence of geriatric depression and with fluctuations of depressive symptoms in the whole group and in subjects who never met criteria for relapse or recurrence during the follow-up period. Memory impairment, disability, medical burden, social support, and history of previous episodes did not significantly influence the outcome of depression in this sample. CONCLUSIONS: Executive dysfunction was found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. These observations, if confirmed, will aid clinicians in identifying patients in need of vigilant follow-up. The findings of this study provide the rationale for investigation of the role of specific prefrontal pathways in predisposing or perpetuating depressive syndromes or symptoms in elderly patients.

Age Factors↗

Age and nortriptyline concentrations in plasma ultrafiltrate.

OBJECTIVES: Since plasma protein binding of tricyclic antidepressants may be relevant to treatment effects and can be influenced by age-associated factors, we examined both plasma ultrafiltrate and total concentrations of nortriptyline (NT) in patients and compared these to age. We hypothesized negative associations with age of both ultrafiltrate NT and the ratio of ultrafiltrate NT to total plasma NT. METHODS: Patients with major depression at a psychiatric service treated with a stable dose of NT were studied. Trough plasma ultrafiltrate NT concentrations and total plasma NT concentrations were measured by high performance liquid chromatography. Concentrations were corrected for dose. RESULTS: Eighty-seven patients aged 26 - 88 years were studied. Ultrafiltrate NT concentrations and the ratio of ultrafiltrate NT to total NT concentrations were both significantly negatively associated with age. Total NT concentrations were not significantly associated with age. CONCLUSIONS: Relatively low ultrafiltrate NT concentrations in older patients may reflect lower tissue exposure at a given total plasma NT concentration. This could be relevant to toxic and therapeutic effects. Studies of relationships between non-bound drug concentrations and NT treatment outcomes across the age span are needed.

Adult↗

Symptoms of striatofrontal dysfunction contribute to disability in geriatric depression.

OBJECTIVE: To examine whether symptoms of striatofrontal dysfunction contribute to disability in geriatric depression. DESIGN: Cross-sectional evaluation of the relationship of specific cognitive impairments, psychomotor retardation, severity of depression, and medical burden to impairment of instrumental activities of daily living. SETTING: Inpatient and outpatient services of a psychiatric university hospital located in a suburban metropolitan area.Patients. One hundred and fifty elderly psychiatric inpatients and outpatients with major depression and cognitive function ranging from normal to moderate dementia. MEASURES: Psychomotor retardation was evaluated with the Hamilton retardation item and executive dysfunction was assessed with the initiation/perseveration (IP) domain of the Dementia Rating Scale. Disability, severity of depression and medical burden were assessed with the Instrumental Activities of Daily Living Index of the Multilevel Assessment Instrument, the Hamilton Depression Rating Scale and the Cumulative Illness Rating Scale-Geriatric, respectively. RESULTS: In the entire sample (N = 150) and in the non-demented subjects (N = 101), stepwise regression analyses revealed that IP and psychomotor retardation were associated with IADL impairment. Additionally, a 'striatofrontal component', which consisted of IP and psychomotor retardation was also significantly associated with IADL impairment in the whole sample, as well as in the non-demented patients. CONCLUSION: Clinical symptoms and neuropsychological findings associated with striatofrontal dysfunction contribute to disability in depressed elderly patients.

Activities of Daily Living↗

Executive functions and P300 latency in elderly depressed patients and control subjects.

The authors asked whether impaired executive functioning and long P300 latency are related dysfunctions and whether they are associated with geriatric depression. A group of 25 elderly depressed patients without dementia and 20 control subjects were assessed on tasks of fluency, initiation and perseveration, the Stroop task, the Wisconsin Card Sorting Test (WCST) perseverative error score, and P300 latency. The groups' performance differed significantly on these tasks and in P300 latency. Longer latency was associated with poorer performance in both groups on all measures except WCST perseverative errors. Regardless of patients' depression status, increased P300 latency predicts poorer performance on executive function tasks requiring speeded performance.

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Diagnosis, treatment, comorbidity, and resource utilization of depressed patients in a general medical practice.

OBJECTIVE: The objective of the study was to determine the effect of depression on the utilization of health care resources, after adjusting for age and comorbidity from data obtained on routine clinical practice. METHOD: The study is an observational cohort of 15,186 patients followed over a one-year period beginning December 1993. Comprehensive demographic, clinical, and utilization data were available from the computerized medical information system generated database of a general internal medicine practice in an urban academic medical center. RESULTS: Four point seven percent of patients carried a provider-coded diagnosis of depression. With regards to utilization of health care resources, even after controlling for age and comorbidity, depressed patients had more primary care visits (5.3 vs. 2.9 visits, p < .001), higher rates of referral to specialists (1.1 vs. 0.5, p < .002), and radiologic tests (0.9 vs. 0.4 tests, p < .001). They had higher total outpatient charges ($1,324 vs. $701, p < .001) and total charges ($2,808 vs. $1,891, p < .001). Depressed patients also had longer length of stay when hospitalized (14.1 vs. 9.5 days, p < .002). CONCLUSIONS: Patients diagnosed as depressed had significantly higher resource utilization of all types, even after controlling for the higher burden of comorbid medical illness associated with depression.

Adult↗

Subtypes of cognitive impairment in depressed older adults.

The authors examined the cognitive profiles of 104 older adults with major depression and empirically identified three subgroups with distinct patterns of cognitive impairment. The entire sample demonstrated memory impairment relative to age-standardized scores, distributed equally across the three cognitive subgroups. One-third of subjects displayed either executive impairment or attentional deficits. The subgroup with executive dysfunction had greater behavioral disability. Identification of executive impairment in depressed older adults may facilitate intervention for disturbances in planning, sequencing, organizing, and abstracting. Demonstrating the presence of subtypes of cognitive impairments in older adults may provide the basis for further investigation of mechanisms of late-life depression and the pathophysiology of antidepressant response. The association of behavioral disability with executive dysfunction can initiate an inquiry into the biology of functional impairment ultimately linking biological research to studies of treatment effectiveness.

Activities of Daily Living↗

Brain computed tomography in geriatric manic disorder.

BACKGROUND: Excess brain changes in geriatric manic patients have been hypothesized. Few neuroimaging studies are available. METHODS: Brain computed tomography scans in geriatric patients with manic disorder (n = 30) were compared to those in same-age control subjects (n = 18). Ratings of cortical sulcal widening (CSW), lateral ventricle-brain ratio (VBR), and related linear measures were determined. RESULTS: Patients had greater CSW scores (Exact p = .002) and VBR (t = 2.51, df = 46, p < .02) compared to control subjects. CSW was positively associated with age at illness onset (rs = .46, p < .01) and age at first manic episode (rs = .53, p < .005). VBR was poorly correlated with CSW and was not associated with these indices of illness course. CONCLUSIONS: These findings support the need for further investigation of relationships between brain structure and clinical features in geriatric mania.

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Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression.

BACKGROUND: Decreased dopamine beta-hydroxylase (DBH) activity has been reported in unipolar psychotic depression. DBH comparisons between elderly delusional and nondelusional depressives and controls and determination of whether pretreatment group differences persist have not been reported. Our objective was to compare DBH activity in elderly delusional major depressives with that of nondelusional depressives and normal control subjects before and after hospital treatment. METHODS: Enzyme activity was assessed after hospital admission. A subsample had predischarge assessments. Treatment was not controlled but accounted for in analyses. Electroconvulsive therapy subjects were medication-free for posttreatment assays. RESULTS: Baseline and predischarge DBH assays were lower in subjects with delusional depression than in either comparison group. Despite high intraindividual correlation, treatment was associated with significant increases in activity in the clinical groups. CONCLUSIONS: Patients with late-life delusional depression have lower DBH activity before and after hospital treatment than age-matched nondelusional patients or normal controls.

Age of Onset↗

Clinical determinants of suicidal ideation and behavior in geriatric depression.

BACKGROUND: The aim of this study was to find clinical characteristics that can identify elderly patients with depression at risk for suicidal ideation and to determine their prognosis. METHOD: Suicidal ideation, past suicidal behavior, severity of depression, cognitive impairment, medical burden, disability, and social support were studied in 354 patients with depression aged 61 to 93 years. The patients had in-person evaluations every 6 months and telephone evaluations for a mean of 1.8 years (SD, 2.2). RESULTS: During the index episode, suicidal ideation was predicted by previous suicide attempts with serious intent (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.37-5.80), severity of depression (OR, 1.09; 95% CI, 1.03-1.16), and poor social support (OR, 1.77; 95% CI, 1.18-2.65). Suicide attempts during the year prior to entry were reported by patients with a severe index episode (OR, 1.05; 95% CI, 1.00-1.11), impaired instrumental activities of daily living (OR, 0.78; 95% CI, 0.67-0.93), and limited impairment in activities of daily living (OR, 1.53; 95% CI, 1.10-2.14). At the initial evaluation, severity of depression, previous attempts, and seriousness of suicidal intent during previous attempts predicted the course of suicidal ideation (concordance correlation, 0.78). During follow-up, contemporaneous severity of depression was the most important determinant of suicidal ideation over time (concordance correlation, 0.88). CONCLUSIONS: Elderly individuals with severe depression, history of suicide attempts with serious intent, and poor social support are most likely to have suicidal ideation and should be targeted for appropriate interventions. Severity of depression is the strongest predictor of the course of suicidal ideation.

Age Factors↗

Prefrontal dysfunction and treatment response in geriatric depression.

BACKGROUND: This study investigated the relationship of clinical, neuropsychological, and electrophysiological measures of prefrontal dysfunction with treatment response in elderly patients with major depression. METHODS: Forty-nine depressed elderly subjects were studied before and after 6 weeks of adequate antidepressant treatment and compared with 22 psychiatrically normal controls. The psychomotor retardation item of the Hamilton Depression Rating Scale, the initiation/perseveration subscore of the Mattis Dementia Rating Scale, and the latency of the P300 auditory evoked potential were used as indices of prefrontal dysfunction. The intensity of antidepressant drug treatment was classified and monitored for a 6-week period. RESULTS: Abnormal initiation/perseveration score, psychomotor retardation, and long P300 latency predicted 58% of the variance in change of depression scores from baseline to 6 weeks (F3= 20.1, P<.001). Depressed patients who remained symptomatic (n = 25) had more abnormal initiation/perseveration scores and longer P300 latency compared with depressed patients who achieved remission (n = 24) and control subjects. There were no differences between the last 2 groups. The association between psychomotor retardation, initiation/perseveration scores, P300 latency, and response to antidepressant treatment could not be explained by differences in demographic and clinical characteristics or treatment intensity between remitted and nonremitted depressed patients. CONCLUSIONS: Prefrontal dysfunction was associated with poor or delayed antidepressant response in depressed elderly patients. This observation, if confirmed, may aid clinicians in identifying candidates for aggressive somatic therapies and for interventions offering structure of daily activities.

Age Factors↗

Consensus statement on the upcoming crisis in geriatric mental health: research agenda for the next 2 decades.

It is anticipated that the number of people older than 65 years with psychiatric disorders in the United States will increase from about 4 million in 1970 to15 million in 2030. The current health care system serves mentally ill older adults poorly and is unprepared to meet the upcoming crisis in geriatric mental health. We recommend the formulation of a 15- to 25-year plan for research on mental disorders in elderly persons. It should include studies of prevention, translation of findings from bench to bedside, large-scale intervention trials with meaningful outcome measures, and health services research. Innovative strategies are needed to formulate new conceptualizations of psychiatric disorders, especially those given scant attention in the past. New methods of clinical and research training involving specialists, primary care clinicians, and the lay public are warranted.

Age Distribution↗

Predictors of antidepressant prescription and early use among depressed outpatients.

OBJECTIVE: The rates of antidepressant recommendation and use were determined in outpatients with major depression receiving services in mental health clinics. Site of service and the patients' sociodemographic and clinical characteristics were investigated as possible predictors. METHOD: Patients admitted to six outpatient clinics were recruited through a two-stage sampling procedure. Patients with major depressive disorder (N = 124) according to the Structured Clinical Interview for DSM-IV--Patient Edition were assessed at admission and 3 months later. RESULTS: Drug therapy was recommended for most patients (71%), and minimal use (at least 1 week) was recorded for 59% of the subjects. White patients were nearly three times as likely to receive a recommendation for antidepressants. Antidepressant recommendation was also associated with severity of depressed mood, recent medication use, and clinic type. Recent antidepressant use was the only variable that predicted whether the patient actually took the recommended medication. CONCLUSIONS: Many patients with depression seeking treatment at community mental health clinics do not receive antidepressant drug therapy. The offer of medication is predicted by patient ethnicity, clinic type, and symptom severity. Minority patients are less likely to be offered antidepressant treatment.

Adolescent↗

The future of psychosocial treatments for elderly patients.

Geriatric psychiatric disorders usually occur in the context of medical illness, disability, and psychosocial impoverishment. Preliminary evidence suggests that psychotherapy can reduce not only psychopathology but also physical complaints, pain, and disability and that it can improve compliance with medical regimens. Psychotherapy has been found effective in treatment of depression related to bereavement and caregiver burden. Modification of available treatment strategies to address infirmity and life adversity may have a major impact on rehabilitation from psychiatric and medical disorders and may reduce utilization of nonpsychiatric health services. Most elderly patients with psychiatric problems prefer to be treated by their primary care physician. Models need to be developed and tested to integrate psychotherapy and other mental health services in primary care settings so that timely and appropriately targeted interventions can be provided.

Aged↗

Brain morphology and response to nortriptyline in geriatric depression.

In geriatric patients with major depression (N=15), the authors compared response to treatment with nortriptyline as it relates to brain morphology assessed by computed tomography. There was a significant negative association between ventricle-brain ratio and response to nortriptyline (rs=-0.63; P=0.015).

Aged↗

Alpha(1)-acid glycoprotein, age, and sex in mood disorders.

Serum alpha(1)-acid glycoprotein (AAG) reportedly can increase with age in the normal population, especially among women. In 33 patients with unipolar major depression or bipolar disorder, serum AAG was measured by age. The authors noted a positive association with age, particularly in depressed female patients (n=18; r(s)=0.61; P<0.01). The authors discuss implications for drug pharmacokinetics. Investigation of AAG in mood disorders needs to take age and sex into consideration.

Adult↗

Late-life depression and functional disability: the role of goal-focused group psychotherapy.

This study compares the efficacy of two time-limited group psychotherapies for depression and functional disability in late life. Goal-focused group psychotherapy (GFGP) utilized focused psychoeducation and skills training to assist each patient in the achievement of individualized goals. Reminiscence therapy (RT) emphasized individual life review to facilitate discussion. Subjects (N = 13), ages 55 and above, with major depression were randomly assigned to one of the two groups. Most were receiving antidepressant treatment. All had failed to achieve full remission. Whereas both treatment groups improved in depressed mood and disability, GFGP subjects had a far greater change in depressive symptomatology and also improved in the areas of hope, hopelessness, anxiety and social functioning.

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P300 latency in geriatric depression.

OBJECTIVE: The purpose of this study was to determine if P300 latency is prolonged in geriatric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease. METHOD: Geriatric patients with unipolar depression (N = 43) and elderly comparison subjects (N = 24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency. RESULTS: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration. CONCLUSIONS: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.

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