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Objectives: To investigate whether pain severity and interference with normal work activities moderate the effects of depression treatment on changes in depressive symptoms over time in older adults in primary care., Design: Patient-randomized, clinical trial., Setting: Multisite: three clinics located in Veterans Affairs Medical Centers., Participants: Adults aged 60 and older (n=524) who screened positive for depression and participated in the Primary Care Research in Substance Abuse and Mental Health for the Elderly Study., Intervention: Integrated care versus enhanced specialty referral care., Measurements: Pain severity, the degree to which pain interferes with work inside and outside of the home, and depressive symptoms were examined at baseline and 3, 6, and 12 months., Results: Intention-to-treat analyses revealed that both treatment groups showed reduced depressive symptoms over time, although self-reported pain moderated reductions in depressive symptoms. At higher levels of pain severity and interference with work activities, improvements in depressive symptoms were blunted. Furthermore, pain interference appeared to have a greater effect on depressive symptoms than did pain severity; in individuals with major depression, pain interference fully accounted for the moderating effects of pain severity on changes in depressive symptoms over time., Conclusion: Pain and its interference with functioning interfere with recovery from depression. Findings highlight the importance of addressing multiple domains of functioning (e.g., physical and social disability) and the degree to which pain and other forms of physical comorbidity may hinder or minimize treatment-related improvements in depressive symptoms.

Objective: Research on the efficacy of antidepressant therapy for depressive symptoms in Alzheimer disease has been hampered by lack of systematic diagnosis, small sample sizes, and short-term follow up. To address these issues, the authors present the design of the Depression in Alzheimer's Disease Study-2 (DIADS-2), a randomized, placebo-controlled multicenter trial to evaluate the efficacy and safety of the selective serotonin reuptake inhibitor sertraline for the treatment of depression in people with Alzheimer disease., Methods: The authors present and discuss the following important aspects of the design: the inclusion of structured psychosocial therapy for the caregivers of all participants; the measurement not only of patient mood outcomes, but also of global and functional outcomes for patients and mood and burden outcomes for caregivers; the ongoing rating of multiple diagnostic criteria to allow nosologic study of depression in Alzheimer disease; the evaluation of both short-term efficacy and longer-term outcomes; the follow up of all patients regardless of whether they complete study treatment; and the unmasking of treatment assignment at the conclusion of each patient's treatment phase., Conclusions: The authors believe these design elements are important features to be included in trials of depression and other neuropsychiatric disturbances in Alzheimer disease.

Background: Although depressive conditions in later life are a major public health problem, the outcomes of minor and subsyndromal depression are largely unknown., Objective: To compare outcomes among patients with minor and subsyndromal depression, major depression, and no depression, and to examine putative outcome predictors., Design: Cohort study., Setting: Patients from primary care practices in greater New York City, and Philadelphia and Pittsburgh, Pennsylvania., Patients: 622 patients who were at least 60 years of age and presented for treatment in primary care practices that provided usual care in a randomized, controlled trial of suicide prevention. Of the 441 (70.9%) patients who completed 1 year of follow-up, 122 had major depression, 205 had minor or subsyndromal depression, and 114 did not have depression at baseline., Measurements: One year after a baseline evaluation, data were collected by using the following tools: Hamilton Depression Rating Scale, the depressive disorders section of the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition), Charlson Comorbidity Index, Multilevel Assessment Instrument for measuring instrumental activities of daily living, Physical Component Summary of the Medical Outcomes Study Short Form-36, and Duke Social Support Index., Results: Patients with minor or subsyndromal depression had intermediate depressive and functional outcomes. Mean adjusted 1-year Hamilton depression score was 10.9 (95% CI, 9.6 to 12.2) for those with initial major depression, 7.0 (CI, 5.9 to 8.1) for those with minor or subsyndromal depression, and 2.9 (CI, 1.6 to 4.2) for those without depression (P < 0.001 for each paired comparison). Compared with patients who were not depressed, those who had minor or subsyndromal depression had a 5.5-fold risk (CI, 3.1-fold to 10.0-fold) for major depression at 1 year after controlling for demographic characteristics (P < 0.001). Cerebrovascular risk factors were not associated with a diagnosis of depression at 1 year after controlling for overall medical burden. Initial medical burden, self-rated health, and subjective social support were significant independent predictors of depression outcome., Limitations: Participants received care at practices that had personnel who had been given enhanced education about depression treatment; 29.1% of participants withdrew from the study before completing 1 year of follow-up., Conclusions: The intermediate outcomes of minor and subsyndromal depression demonstrate the clinical significance of these conditions and suggest that they are part of a spectrum of depressive illness. Greater medical burden, poor subjective health status, and poorer subjective social support confer a higher risk for poor outcome.

Objective: The objective of this study was to use data from daily diaries to characterize the day-to-day variability in positive and negative affects, and the relationship between daily events and daily affects in primary care patients with late-life depression., Method: Daily diary data were obtained from primary care patients with major depression (N = 25) and other depressive disorders (N = 33); data from a two-week period were compared with those from elderly normal volunteer comparison subjects (N = 70) who participated in other studies., Results: There was significant day-to-day variability in negative affect in patients with major depression and other depressive disorders. Dysphoric days (days with a negative affect ratings that occurred once every two weeks in normal subjects) represented 65.3% (standard deviation [SD]: 37.1) of days in those with major depression and 50.6% (SD: 37.6) in those with other depression versus 7.7% (SD: 16.3) in normal subjects (F = 36.0, p <0.001). The groups did not differ significantly in the number of positive and negative events reported, but the proportion of dysphoric days that occurred in association with negative events was greater in normal subjects than in those with major depression. Mixed-effects analyses demonstrated that patients with major depression had blunted positive affective responses to positive events, consistent with impairments in hedonic processes, and that patients with other depressions exhibited heightened negative affective responses to negative events, greater than those in normal subjects and patients with major depression., Conclusions: Diary methods demonstrated characteristics of late-life depression that have not been identified with assessment methods that have lower time resolution.

Objectives: The purpose of this project was to assess the utility and feasibility of a telephone-based systematic clinical assessment service, the Behavioral Health Laboratory (BHL), in the context of primary care. The BHL is a clinical service that provides primary care providers with an assessment and a summary of mental health and substance abuse (MH/SA) symptoms and provides treatment decision support, including triage to specialty MH/SA services. The BHL was implemented to assist in the evaluation of patients who screened positively for depression at an annual clinical appointment or who were identified through routine care., Methods: Results from systematic screening of primary care patients were extracted during a period of 6 months prior to implementation of the BHL and after implementation of the BHL. Descriptive results of the 580 evaluations conducted during this time were available., Results: Results suggest an association between the implementation of the BHL and an increase in the proportion of patients screened for depression in primary care. In addition, there was an increase in the proportion of patients who screened positively (2.8% vs 7.0%). The BHL was successful in providing a comprehensive assessment for 78% of those referred. Significant co-occurring mental illness and substance misuse were found among those assessed., Conclusions: Introducing the BHL into primary care was associated with an apparent change in clinical practice in primary care at the Philadelphia VA Medical Center. Not only were more patients identified, the broad-based approach of the BHL identified significant comorbidity with alcohol misuse, illicit drugs, and suicidal ideation, symptoms likely to have been missed in routine clinical practice. The BHL offers a practical, low-cost method of assessment, monitoring, and treatment planning for patients identified in primary care with MH/SA needs.

Background: This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women., Methods: Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task., Results: Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol., Conclusions: Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.

Objective: This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old.", Method: This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression., Results: A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%)., Conclusions: In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%.

Depression in Parkinson's disease (PD) is common, but little is known about its recognition and treatment. The authors report the antidepressant experience (N = 100) and outcome of depression assessment (n = 77) of a convenience sample of patients at a PD center. Subjects were assessed with a psychiatric and neurological battery, and information was gathered on depression treatment. One third (34%) of subjects met criteria for a depressive disorder, and two thirds (65%) of them were not currently receiving antidepressant treatment. Approximately one quarter (23%) of subjects were taking an antidepressant, but almost half (47%) of them still met criteria for a depressive disorder. Few antidepressant users with persistent depression had received either antidepressant treatment at dosages within the highest recommended range (11%) or more than 1 antidepressant trial (33%). Most depressed patients are untreated, and half of antidepressant users remain depressed, suggesting that even when delivered, treatment is often inadequate or ineffective.

Background: In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents., Method: The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial., Results: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers., Conclusion: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.

Objectives: Previous studies have demonstrated an association between major depression and physical disability in late life. The objectives of this study were to examine the relationship between specific medical illnesses and the outcomes of treatment for late-life depression., Design: The study was a longitudinal assessment of medical illness, depression, and disability. Patients were assessed during an initial inpatient psychiatric hospitalization and 3 months postdischarge., Setting: All patients were initially evaluated after admission to one of 71 inpatient psychiatric treatment facilities., Participants: A sample of 671 older patients who received inpatient treatment for depression was evaluated at entry into the hospital and 3 months after discharge., Measurements: Depressive symptoms were measured using the Geriatric Depression Scale. Disability was measured using the instrumental activities of daily living scale and the Medical Outcomes Study 36-item short form. Medical illness was assessed using the medical illness checklist., Results: As previously reported, physical disability and the total number of medical illnesses were significantly related to change in depressive symptoms. In this study, we find that arthritis, circulatory problems, a speech disorder, or a skin problem, but not other general medical conditions, were related to a worse outcome with respect to depression symptoms. The effect of these problems was statistically and clinically significant. After controlling for pretreatment disability, arthritis and skin problems continued to predict a worse outcome. However, the apparent effect of each of these conditions was mediated by the residual disability after treatment., Conclusion: The results of this study support the hypothesis that certain somatic disorders play a role in the treatment response of late-life depression and suggest that the effect of specific illnesses on depression may be mediated by the presence of functional disability.

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.

This review provides the rationale and background for the development of diagnostic criteria for depression of Alzheimer disease (AD), including risk factors and neurobiological correlates, epidemiology, and clinical characteristics, along with course, assessment, treatment, economics, a description of the criteria, and future research directions. Overall, there is substantial research to suggest that the depression that may co-occur with AD is different from other depressive disorders. Further research is needed to better define core symptoms, clinical course, and efficacy of treatments.

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.

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.

The authors examined the effects of alcohol use on the short-term and 3-4-month treatment outcomes of patients with late-life depression. Patients (N=2,666) were assessed for symptoms of depression, alcohol use, and disability during an initial inpatient hospitalization and then 3-4 months postdischarge. Contrary to our hypothesis that alcohol consumption imparted a significant additive detriment to treatment outcome in patients already suffering from major depression, the results suggest that treatment was effective even in those with concomitant use of alcohol. Moreover, there appeared to be an added benefit when even modest alcohol consumption was decreased among elderly patients suffering from depression.

Objectives: The objective of this study was to examine the relationship between functional disability and improvement in late life depression after acute inpatient treatment., Design: The study was a longitudinal assessment of depression and disability. Patients were assessed during an initial inpatient hospitalization and then 3 months postdischarge., Setting: All patients were evaluated initially after admission to one of 71 inpatient psychiatric treatment facilities., Participants: The study comprised of 2572 patients older than age 60 who were relatively cognitively intact and experiencing significant depressive symptoms., Measurements: Depressive symptoms were measured using the Geriatric Depression Scale. Disability was measured using the Instrumental Activities of Daily Living Scale and the Medical Outcomes SF-36., Results: Depressive symptoms improved in the majority of patients. Moreover, improvement in depressive symptomatology was significantly related to improvement in instrumental activities of daily living (IADLs) and to health-related quality of life as measured by the SF-36. This relationship was strongest among those who initially presented with some disability in IADLs., Conclusions: This work underscores further the disabling nature of depression. Moreover, findings from this study suggest that treatment focused on depression can lead to significant improvements in both depressive symptoms and functional abilities. However, the results also suggest that the relationship between depression and disability is complex and that the effect of treating depression is not the only factor in the reversal of disability.

The authors conducted a randomized, double-blind, 10-week clinical trial of two doses of nortriptyline in eight nursing homes. Sixty-nine patients, average age 79.5 years, were randomized to receive regular doses (60 mg-80 mg/day) vs. low doses (10 mg-13 mg/day) of nortriptyline. Among the more cognitively intact patients, there was a significant quadratic relationship defining a "therapeutic window" for nortriptyline plasma levels and clinical improvement. There were also significant differences in plasma level-response relationships between depressed patients who were cognitively impaired and those who were more cognitively intact. Depression remains a syndrome that responds to specific treatment, even in frail nursing home patients, and those depressions that occur in patients with significant dementia may represent a treatment-relevant condition with a different plasma level-response relationship than in depression alone.

Studies have demonstrated that the selective serotonin reuptake inhibitor antidepressants have similar efficacy to other agents, such as tricyclic antidepressants. However, data are limited for direct comparisons with other antidepressants. The authors conducted a contemporaneous comparison of nursing home residents treated with open-label sertraline in doses up to 100 mg/day with nursing home residents treated in a double-blind randomized study of low vs. regular doses of nortriptyline. There were 97 patients enrolled in the study (28 treated with sertraline), with an average treatment duration of 55 days. There were no differences in the tolerability of sertraline vs. nortriptyline. However, in this group of frail older adults, sertraline was not as effective as nortriptyline for the treatment of depression.

Alcoholism and depression are two of the most common and disabling mental illnesses in late life. This study is a descriptive report of a sample of 49 adults who had recently been convicted of Driving Under the Influence of alcohol (DUI). A lifetime history of alcohol abuse or dependence was present in 48 subjects (98%), while a depressive disorder occurred in 24 (49%) of the subjects. Concurrent alcoholism and depression, present in 12 subjects (24.5%), produced greater self-reported disability compared to those subjects with alcoholism alone. One-year longitudinal follow-up was available on 31 subjects (63.3%). Over the course of one year, there were no changes in drinking behavior, depressive symptoms, or self-reported quality of life. These data support previous studies that suggest greater disability in patients with concurrent mental illnesses.

Depressive disorders--both major depression and other less severe but nonetheless clinically significant depressions--are common comorbidities, components, or complications of dementia. Depression with reversible cognitive impairment may be a prodrome for dementia rather than a separate and distinct disorder. Recent research has demonstrated that both the diagnosis of major depression and the assessment of typical depressive symptoms can be conducted reliably, even in patients with mild-to-moderate levels of cognitive impairment. Self-ratings of depressive symptoms with the Geriatric Depression Scale remain valid in patients with Mini-Mental State Examination scores of at least 15. Among interviewer-administered instruments, the Hamilton Rating Scale for Depression and the Cornell Scale are the best established. Potential difficulties with assessment include problems with ascertainment (because families, in general, report greater depression in patients than do clinicians) and the ambiguity of symptoms (because apathy and related symptoms can result from both depression and Alzheimer's disease). Brain changes due to Alzheimer's disease may lead to fundamental differences in drug responses. Nevertheless, randomized clinical trials have demonstrated that depression in dementia responds to specific psychopharmacologic or psychosocial treatments.

Both depression and dementia can lead to failure to thrive (FTT). Depression can lead to FTT by two routes: a direct path related to decreased appetite as a symptom of depression; and an indirect path related to the effect of depression in increasing disability. Depression associated with FTT should usually be treated with antidepressant medication. In Alzheimer's patients with FTT, the thrust of treatment is the identification and treatment of the medical and psychiatric comorbidities and the appropriate titration of environmental supports.

Objective: To reexamine the conclusions of the 1991 National Institutes of Health Consensus Panel on Diagnosis and Treatment of Depression in Late Life in light of current scientific evidence., Participants: Participants included National Institutes of Health staff and experts drawn from the Planning Committee and presenters of the 1991 Consensus Development Conference., Evidence: Participants summarized relevant data from the world scientific literature on the original questions posed for the conference., Process: Participants reviewed the original consensus statement and identified areas for update. The list of issues was circulated to all participants and amended to reflect group agreement. Selected participants prepared first drafts of the consensus update for each issue. All drafts were read by all participants and were amended and edited to reflect group consensus., Conclusions: The review concluded that, although the initial consensus statement still holds, there is important new information in a number of areas. These areas include the onset and course of late-life depression; comorbidity and disability; sex and hormonal issues; newer medications, psychotherapies, and approaches to long-term treatment; impact of depression on health services and health care resource use; late-life depression as a risk factor for suicide; and the importance of the heterogeneous forms of depression. Depression in older people remains a significant public health problem. The burden of unrecognized or inadequately treated depression is substantial. Efficacious treatments are available. Aggressive approaches to recognition, diagnosis, and treatment are warranted to minimize suffering, improve overall functioning and quality of life, and limit inappropriate use of health care resources.

The prevalence of psychiatric disorders was determined in a sample of 196 VA nursing home residents who were interviewed using the modified Schedule for Affective Disorders and Schizophrenia (mSADS). Of the 160 subjects for whom data were available, 86% had a diagnosis of at least one psychiatric disorder. The prevalence of clinically significant cognitive impairment was 60.6% and of major depression 13.8%. Of 110 residents for whom alcohol histories were obtained, 32 (29%) had a lifetime diagnosis of alcohol abuse. The degree of impairment in activities of daily living improved significantly from the time of admission to the time of the evaluation (average 1.4 years) among those who were recently abusing alcohol compared to those who formerly abused alcohol and those who never abused alcohol. The effect is clinically as well as statistically significant and has the potential benefit of reducing caregiver burden and health care costs for the elderly.

Ratings on a 10-item affect checklist yielding composite positive affect and negative affect scores were made daily for 30 days by older people in residential care: 19 were diagnosed as having major depression, 21 had minor depression, and 37 were without psychiatric diagnosis ("normal"). Mean levels of positive affect were highest in normal people and least in those with major depression; negative affect was lowest in normal ones and highest in those with a major depression. Variability was least among those with major depression in positive affect and among normal people in negative affect, while residents with minor depression showed some tendency, although inconsistent, toward greater day-to-day variability in positive affect. Patterns of invariance were such that those with major depression tended to be consistently lacking in positive affect but were variable in negative affect; normal people showed variability in positive affect but a relatively unvarying lack of negative affect. Clinical major depression was thus characterized less by "pervasive" depressive affect than by anhedonia.

To explore the extent to which treatment of depression affects survival, we evaluated the association between use of antidepressant medications and death rates among the residents of a large residential-care facility for the elderly using a retrospective record-review study (N = 624). One year survival, among those taking antidepressants (10.9%), was 11.8% compared to 11.1% among the remainder of the population. A second study followed a group of 32 patients in the same institution who had participated in a therapeutic trial of nortriptyline treatment for major depression. Patients who experienced adverse medical events during treatment exhibited significantly increased mortality; among treatment completers, there was no significant relationship between mortality and therapeutic response. These findings suggest that the inability to tolerate treatment with an antidepressant can be considered a manifestation of physiologic frailty and increased vulnerability to mortality from disease. The previously reported decrease in survival among residential-care patients with major depression is not paralleled by a similar effect in those taking antidepressants. This may reflect selection factors with respect to the ability to tolerate antidepressants, rather an effect of treatment.

As emphasized in the recent NIH Consensus Statement on the Diagnosis and Treatment of Depression in Late Life, depression in the elderly is a persistent or recurrent disorder that can result from psychosocial stress or physiological effects of disease and can lead to excess disability, cognitive impairment, increased symptoms from medical illness, physiological effects, increased utilization of health care services, and increased rates of suicide and nonsuicide mortality. Primary prevention can target high-risk groups including those with specific medical illnesses, disabling chronic diseases, widows/widowers, and spousal caregivers. Secondary prevention of recurrences of major depression is possible through maintenance treatment with antidepressant medications. Secondary prevention of behavioral complications such as suicide and alcoholism and of excess disability, morbidity, and utilization of general health services in patients with psychiatric-medical comorbidity can be facilitated by systematic approaches to case identification and treatment for depression in medical patients.

The priorities for future research from the NIH Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life, as republished in the previous article, included recommendations to "conduct clinical trials and observational studies of treatment in the very old, the elderly in institutional setting, and the elderly with medical illnesses," that is, in the frail elderly. The present article reviews recent research in this field and outlines the potential for future developments. The importance of these areas of investigation follows from epidemiological findings suggesting that the prevalence of major depression in community populations, in general, decreases as a function of age but that depressions of all types occur more frequently in the "oldest-old," in patients seen in medical care settings, and in those with chronic disease and disability. The psychopharmacological literature, as summarized for the Consensus Conference in the review by Salzman and the meta-analyses of Klawansky, Greenhouse, and Schneider, indicates that antidepressant medications remain effective in elderly patients with moderate to severe degrees of major depression. Questions remain, however, about the value of drug treatment for those depressions that are most common in late life, including those that occur in extremely old patients and in patients with significant medical illness.

This study examined the association between depression and mortality among a group of nursing home and congregate apartment residents (initial n = 898) over a 30-month period. Baseline [Time 1 (T1)] and 1-year follow-up [Time 2 (T2)] assessments yielded research-based diagnoses of possible major, minor, or no depression, along with measures of functional disability, cognitive status, and physician-rated health. Event history analyses were used to assess differential mortality as a function of level of depression after T1 and of change in depressive status from T1 to T2. Significant effects for T1 depression at 6, 12, and 18 months after the interview reflected an increased death rate among possible major depressives as compared with other respondents. An effect of change in depressive status from T1 to T2 appeared to be caused by long-term negative effects of T1 depression. Finally, none of the observed associations remained significant when controlled for effects of physical health, functional disability, and cognitive status. Thus, the effects of depression on mortality among this sample appeared to be attributable strictly to the correlation of depression with ill health. However, cautious interpretation is recommended inasmuch as causal paths between depression, ill health, and death remain unclear.

Interrelations between depression (Geriatric Depression Scale) and cognitive impairment (Blessed test) were examined among 201 nursing home and congregate apartment residents in a 2-year, 3-wave study. In structural equations models that controlled autocorrelations and within-occasion correlated residuals, introducing paths from depression to subsequent cognitive status significantly reduced unexplained variance, whereas paths from cognitive status to subsequent depression did not. Subsidiary analyses indicated that the relation of depression to subsequent cognitive status was strongest among persons with borderline (vs. impaired or intact) cognitive status, but only for the first time interval. Discussion addresses explanations for obtained results and implications for monitoring and treating depression among elderly long-term care residents.

Nursing home and congregate apartment residents (N = 598) were classified on the basis of a DSM-IIIR symptom checklist as suffering possible major, minor, or no depression; they also completed the Geriatric Depression Scale (GDS) and the Profile of Mood States (POMS). Possible major depressives reported more intense pain and a greater number of localized pain complaints than did minor depressives; nondepressed individuals reported the least intense pain and fewest localized complaints. The effect remained strong even when functional disability and health status were controlled statistically. Both pain intensity and number of localized complaints were correlated with GDS and POMS factor scores, but strength and direction of associations varied with level of depression. Item-by-item examination of localized complaints again indicated that more depressed individuals were more likely to report pain, particularly where physicians had identified a physical problem that might account for the pain. Results are compared with previous research on pain among younger individuals. Implications for treatment of depressed elderly are discussed.

A significant drug-placebo difference was found in a double-blind, placebo-controlled study of nortriptyline for treatment of major depression among frail elderly patients living in an institutional setting. This finding confirms the validity of the DSM-III-R diagnosis of major depression and establishes the need for specific psychiatric services for the chronically ill elderly living in nursing homes and congregate housing facilities. The incidence of adverse events requiring early termination of treatment was 34%, demonstrating the vulnerability of these patients and their need for careful monitoring during treatment. High levels of self-care disability and low levels of serum albumin were both associated with decreased therapeutic responses, demonstrating the need for further research on psychopathology in these settings.

We have compared levels of albumin and serum amino acids in a group of 87 recent admissions to a nursing home, average age 83 years, with a group of healthy moderately old subjects, average age 69 years. We found that the nursing home group was characterized by decreased levels of albumin, by increased total levels of the measured amino acids, and by increased levels of the nonessential amino acids. In contrast, there were no significant group differences in the essential amino acids. Among the nursing home patients, there was a negative correlation between essential amino acids and disability, consistent with nutritional deficits in the more disabled patients, and a positive correlation between essential amino acids and subjective complaints of pain, suggesting that pain is associated with breakdown or mobilization of endogenous protein stores. Though the nursing home patients had decreased serum levels of tryptophan, there was no association between serum tryptophan or other variables that could be related to the availability of tryptophan for transport into brain, with ratings of either depression or pain. Glutamine levels were significantly increased in the nursing home residents, and among these patients they were positively correlated with measures of cognitive impairment.

Sir Martin Roth has stated, "where there is depression, there is hope," to emphasize the fact that depression can be a treatable source of excess disability, even when it is superimposed upon irreversible chronic medical illness. Both the potential benefits and the risks of antidepressant medications are increased in the frail elderly. This article presents an approach toward defining who should be treated and for ensuring that elderly patients receive adequate treatment.

The prevalence of depression among nursing home residents was estimated by screening a group of residents selected from a random sample on the basis of cognitive status; it ranged from 18-20% for major depression to 27-44% for other dysphoric states. Though individual patients were observed to change over a 6-month period, depression as assessed with the Geriatric Depression Scale was, in general, persistent. Major depression was clinically confirmed in 8 of 10 patients identified at screening. It was characterized by medical disorders that complicated diagnosis and treatment, and by increased mortality relative to the rest of the population.