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The purpose of this symposium is to inform participants of programs at the National Institute of Mental Health (NIMH) that support research efforts on aging and mental health. The session will present an overview of NIMH's extramural research divisions, the aging research these programs currently support, and the Institute's programmatic interests and priorities with respect to future studies. Participants will also learn about available funding mechanisms, and general procedures for submitting grant applications. Furthermore, the session will describe trends and new developments at NIMH that have implications for aging-related research, including recent program announcements, the operations of an internal aging consortium that has been formed to coordinate and expand the Institute's activities relative to aging research, and a strategic plan for mood disorders research. Participants will be encouraged to ask questions and identify issues of particular interest for discussion during the session.

OBJECTIVE: The authors compared the effectiveness of cognitive therapy and pharmacotherapy as second-step strategies for outpatients with major depressive disorder who had received inadequate benefit from an initial trial of citalopram. Cognitive therapy was compared with medication augmentation and switch strategies.METHOD: An equipoise-stratified randomization strategy was used to assign participants to either augmentation of citalopram with cognitive therapy (N=65) or medication (N=117; either sustained-release bupropion [N=56] or buspirone [N=61]) or switch to cognitive therapy (N=36) or another antidepressant (N=86; sertraline [N=27], sustained-release bupropion [N=28], or extended-release venlafaxine [N=31]). Treatment outcomes and the frequency of adverse events were compared.RESULTS: Less than one-third of participants consented to randomization strata that permitted comparison of cognitive therapy and pharmacotherapy. Among participants who were assigned to second-step treatment, those who received cognitive therapy (either alone or in combination with citalopram) had similar response and remission rates to those assigned to medication strategies. For those who continued on citalopram, medication augmentation resulted in significantly more rapid remission than augmentation with cognitive therapy. Among those who discontinued citalopram, there were no significant differences in outcome, although those who switched to a different antidepressant reported significantly more side effects than those who received cognitive therapy alone.CONCLUSIONS: After an unsatisfactory response to citalopram, patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients' willingness to accept different second-step treatment approaches. METHOD: Participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who had unsatisfactory outcomes after initial treatment with citalopram were eligible for a randomized second-step treatment trial. An equipoise-stratified design allowed participants to exclude or include specific treatment strategies. Analyses were conducted to identify factors associated with the acceptability of the following second-step treatments: cognitive therapy versus no cognitive therapy, any switch strategy versus any augmentation strategy (including cognitive therapy), and a medication switch strategy only versus a medication augmentation strategy only. RESULTS: Of the 1,439 participants who entered second-step treatment, 1% accepted all treatment strategies, 3% accepted only cognitive therapy, and 26% accepted cognitive therapy (thus, 71% did not accept cognitive therapy). Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram were more likely to accept a switch strategy as compared with an augmentation strategy. Those with concurrent drug abuse and recurrent major depressive disorder were less likely to accept a switch strategy. CONCLUSIONS: Few participants accepted all treatments. Acceptance of cognitive therapy was primarily associated with sociodemographic characteristics, while acceptance of a treatment switch was associated with the results of the initial treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHOD: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of /=11 (HRSD(17)>/=14) defined relapse. RESULTS: The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. CONCLUSIONS: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. METHOD: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score

OBJECTIVE: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T(3)) augmentation as a third-step treatment for patients with major depressive disorder. METHOD: A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T(3) (up to 50 microg/day; N=73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score

Objective: Few controlled studies have addressed the issue of which antidepressant medications should be recommended for outpatients who have not responded to multiple treatment trials. This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant (nortriptyline) following two prospective, consecutive, unsuccessful medication treatments for nonpsychotic major depressive disorder.Method: Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks (first step) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone (second step), adult outpatients (N=235) with nonpsychotic major depressive disorder were randomly assigned to 14 weeks of treatment with mirtazapine (up to 60 mg/day) (N=114) or nortriptyline (up to 200 mg/day) (N=121). The primary outcome, symptom remission, was defined a priori as a total exit score of /=50% reduction in score from baseline).Results: For mirtazapine, remission rates were 12.3% and 8.0% per the Hamilton and QIDS-SR(16) scores, respectively. For nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS-SR(16) response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither response nor remission rates statistically differed by treatment, nor did these two treatments differ in tolerability or adverse events.Conclusions: Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article reports on the research which reveals that patients with major depressive disorder (MDD) and have failed three trials have low remission rates. The Sequenced Treatment Alterntives to Relieve Depression (STARD), which was funded by the U.S. National Institute of Mental Health, assesses the effectiveness of adequately delivered treatments in outpatients who have MDD includes four levels of treatment. The study states that the course of treatment with each medication in level 3 was similar for both medications. INSET: Editorial cites value of STAR⋆D study.

Unlabelled: This report presents the rationale, design, and baseline sample characteristics for the REVAMP study. This project is a multisite clinical trial designed to evaluate the efficacy of augmenting state-of-the-art pharmacotherapy with psychotherapy in chronically depressed patients who fail to respond or respond incompletely to an initial trial of antidepressant medication., Background: Chronic forms of major depression disorder (cMDD) are longitudinally continuous forms of major depressive disorder (MDD), and may account for a significant portion of the societal burden of disease associated with M D D. Antidepressant medications and depression-focused psychotherapies have been shown to be effective for cMDD, though the majority fail to achieve remission following an acute course of treatment. There is a pressing need to evaluate whether the outcomes obtained from a well implemented medication algorithm combined with depression-focused psychotherapy can significantly enhance outcomes for cMDD., Rationale: Although there is evidence for the effectiveness of depression-focused psychotherapy for the treatment of cMDD, this is the first prospective, randomized, controlled trial investigating psychotherapy as an augmentation strategy for patients with cMDD incompletely responsive to a trial of antidepressant medication., Specific Aims: The REVAMP study has three specific aims: first, to compare the efficacy of adding psychotherapy to a medication change versus changing medication alone in chronic depressives with partial response or nonresponse to an initial trial of antidepressant medication; second, to test efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) as an augmentation strategy by comparing it to Supportive Psychotherapy (SP); and third, to test a hypothesized mechanism of therapeutic action of CBASP by examining whether patients receiving CBASP exhibit significantly greater improvements in social problem solving than patients receiving adjunctive SP or continued medication alone. As a subsidiary aim, the study also compares the effects of the three randomized treatments on psychosocial outcomes., Design: The study involves two 12-week phases. During Phase 1, patients with cMDD receive antidepressant monotherapy selected according to an algorithm that takes into account their prior treatment history. Their pattern of response is evaluated, those with no response at 8 weeks or less than a full response at 12 weeks advance to Phase 2. At the beginning of Phase 2, patients who did not respond to the initial antidepressant monotherapy during Phase 1 are switched to the next medication in the pharmacotherapy algorithm and randomly assigned in a 2:2:1 ratio to one of three treatment cells: 16 sessions of either CBASP (40% of randomizations) or SP (40%) added to pharmacotherapy, or medication alone (20%) with no added psychotherapy. Similarly, patients achieving a partial response during Phase 1 have their initial medication augmented with a second antidepressant agent during Phase 2 and are randomly assigned to either CBASP, SP, or medication alone. Patients who achieve remission during Phase 1 are not randomized to Phase 2, but rather are monitored monthly for an additional 12 weeks., Comment: Recent sequential treatment studies have provided state-of-the-art knowledge about the need for multiple steps in order to achieve remission. The current study, therefore, provides an important next step in understanding the role of depression-focused psychotherapy in a treatment algorithm so essential in the management of difficult-to-treat depression such as chronic forms of major depression.

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.

STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessments.

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.

As part of the National Institute of Mental Health Strategic Plan for Mood Disorders Research effort, the Clinical Trials and Translation Workgroup was asked to define priorities for clinical trials in mood disorders and for research on how best to translate the results of such research to clinical practice settings. Through two face-to-face meetings and a series of conference calls, we established priorities based on the literature to date and what was known about research currently in progress in this area. We defined five areas of priority that cut across developmental stages, while noting that research on adult mood disorders was at a more advanced stage in each of these areas than research on child or geriatric disorders. The five areas of priority are: 1) maximizing the effectiveness and cost-effectiveness of initial (acute) treatments for mood disorders already known to be efficacious in selected populations and settings when they are applied across all populations and care settings; 2) learning what further treatments or services are most likely to reduce symptoms and improve functioning when the first treatment is delivered well, but the mood disorder does not remit or show adequate improvement; 3) learning what treatments or services are most cost-effective in preventing recurrence or relapse and maintaining optimal functioning after a patient's mood disorder has remitted or responded maximally to treatment; 4) developing and validating clinical, psychosocial, biological, or other markers that predict: a) which treatments are most effective, b) course of illness, c) risk of adverse events/tolerability and acceptability for individual patients or well-defined subgroups of patients; 5) developing clinical trial designs and methods that result in lower research costs and greater generalizability earlier in the treatment development and testing process. A rationale for the importance of each of these priorities is provided.

Great strides have been made in developing psychosocial interventions for the treatment of depression and bipolar disorder over the last three decades, but more remains to be done. The National Institute of Mental Health Psychosocial Intervention Development Workgroup recommends three priorities for future innovation: 1) development of new and more effective interventions that address both symptom change and functional capacity, 2) development of interventions that prevent onset and recurrence of clinical episodes in at-risk populations, and 3) development of user-friendly interventions and nontraditional delivery methods to increase access to evidence-based interventions. In each of these areas, the Workgroup recommends systematic study of the mediating mechanisms that drive the process of change and the moderators that influence their effects. This information will highlight the elements of psychosocial interventions that most contribute to the prevention and treatment of mood disorders across diagnostic groups, populations served, and community settings. The process of developing innovative interventions should have as its goal a mental health service delivery system that prevents the onset and recurrence of the mood disorders, furnishes increasingly effective treatment for those who seek it, and provides access to evidence-based psychosocial interventions via all feasible means.

The existing evidence paints an unclear picture of whether an association exists between depression and memory impairment. The purpose of this investigation was to determine whether depression is associated with memory impairment, whether moderator variables determine the extent of this association, and whether any obtained association is unique to depression. Meta-analytic techniques were used to synthesize data from 99 studies on recall and 48 studies on recognition in clinically depressed and nondepressed samples. Associations between memory impairment and other psychiatric disorders (e.g., schizophrenia, dementia) were also examined. A significant, stable association between depression and memory impairment was revealed. Further analyses indicated, however, that it is likely that depression is linked to particular aspects of memory, the linkage is found in particular subsets of depressed individuals, and memory impairment is not unique to depression.

Confirmatory factor analysis was used to examine the appropriateness of using with elderly persons Levenson's multidimensional locus of control (LoC) scale that measures beliefs in Internal Control (I), Control by Powerful Others (P), and Chance (C). Data were obtained from elderly individuals in Florida and Texas and reformulated to allow cross-validation at each step in a series of model evaluations. Results indicated that Levenson's three-factor specification of control was not a valid representation of the samples' responses. A model that specified the elimination of eleven unreliable items and the formation of a new external control factor that was based on the remaining C and P items provided an adequate fit to the data for both samples. The failure to confirm Levenson's three-factor structure poses a construct-validity and measurement-equivalence problem when making age-based comparisons of LoC scores.

Levenson's Internal, Powerful Others, and Chance scales were administered to 305 college undergraduates and 117 community-living elderly. On the basis of their highest standard score, sixty young and sixty elderly participants were then classified into High Internal, High Powerful Others, and High Chance categories. The young sample was administered the Zung Depression Scale and the debilitating anxiety scale of the Alpert-Haber Achievement Anxiety Test, while the elderly were given the Beck Depression Inventory, the Depression and Anxiety Scales of the Profile of Mood States, and rated on the Hamilton Rating Scale for Depression. Contrary to previous results, the elderly sample was more external (on the Chance dimension) than the young. As predicted, there was a significant relationship linking a pattern of high internality and low belief in powerful others with low depression in the elderly, but not in the young. Applicability of these findings to placement and intervention strategies is discussed.

The factor structure of the Beck Depression Inventory short form (BDI-SF) was investigated in two elderly samples, with the method of confirmatory factor analysis. Four models previously reported for the BDI-SF in the general adult population were compared for goodness of fit to the data for elderly respondents, and the best-fitting model was adjusted further for these data. Each step in the analyses of the BDI-SF responses of 199 elderly subjects from Tampa, Florida, was cross-validated with data from a second sample of 113 elderly subjects from Houston, Texas. The results confirmed that the three-factor model reported by Reynolds and Gould (1981) adequately fit the data from both elderly samples. The three identified factors were termed Negative Self-Esteem, Anergy, and Dysphoria and were considered to correspond with the cognitive, behavioral, and affective components that generally are thought to be part of the depressive syndrome. The internal consistency of the overall BDI-SF was .74 and .80 in the Tampa and Houston samples, respectively. These findings provide evidence for the construct validity of the BDI-SF by confirming that it displays a factor structure in the aged similar to that observed in the general adult population.

The purpose of this study was to examine the relationship of late-life depression to memory complaint and objective performance in a recognition memory task. Fifty-seven individuals between the ages of 58 and 88 were evaluated for depression using the Beck Depression Inventory (short form). They were then shown two stimulus lists, each consisting of high-imagery and low-imagery words. Recognition for these words was subsequently tested. Error rates and nonparametric signal detection measures were analyzed as indices of performance. Respondents gave global self-assessments of memory and, during the recognition task, also made self-ratings of performance. Depressed individuals showed more conservative response biases than nondepressed respondents, reflected in a higher false-negative error rate but a lower false-positive rate. Neither overall memory sensitivity as assessed by signal detection analysis nor self-ratings of performance were related to depression, though global memory self-ratings were. Elderly depressed individuals thus presented a pattern of greater memory complaint and unwillingness to venture responses in spite of showing small or no information-processing deficits.

To clarify the role of memory impairment in the aged as a normal or psychopathological phenomenon, 153 persons 50-years-old and over with varying degrees of depression and altered brain function were compared for their complaints about memory and actual performance on a series of memory tests. It was found that while performance varied with altered brain function, complaint was related to level of depression, regardless of performance. Exaggerated memory complaint was considered one manifestation of a general pattern of discrpant reporting of symptoms by depressed persons, and apparently related to an underlying personality factor. The complaint of superiority of remote over recent memory was not substantiated empirically, but was considered part of the pattern of stereotyped language and attitudes characteristic of depressed persons.