Depression: Alexopoulos GS

Alexopoulos GS, Katz IR, Reynolds CF, Carpenter D, Docherty JP, Anonymous00334. · No affiliation provided · Postgrad Med. · Pubmed #17205639 No free full text.

Abstract: 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.

Alexopoulos GS. · No affiliation provided · Am J Psychiatry. · Pubmed #18593780 links to  free full text

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Alexopoulos GS. · Department of Psychiatry, Weill-Cornell Institute of Geriatric Psychiatry, White Plains, New York, USA. · Biol Psychiatry. · Pubmed #17157096 No free full text.

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Alexopoulos GS. · No affiliation provided · J Am Geriatr Soc. · Pubmed #12890087 No free full text.

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Alexopoulos GS. · No affiliation provided · Am J Psychiatry. · Pubmed #12727680 links to  free full text

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Alexopoulos GS, Anonymous00210. · No affiliation provided · Int J Geriatr Psychiatry. · Pubmed #11424163 No free full text.

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Alexopoulos GS. · No affiliation provided · Am J Psychiatry. · Pubmed #11384886 links to  free full text

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Alexopoulos GS. · No affiliation provided · Am J Geriatr Psychiatry. · Pubmed #11156748 No free full text.

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Alexopoulos GS, Raue PJ, Kanellopoulos D, Mackin S, Arean PA. · Department of Psychiatry, Weill Cornell Medical College, White Plains, NY 10605, USA. · Int J Geriatr Psychiatry. · Pubmed #18213605 No free full text.

Abstract: BACKGROUND: The 'depression executive dysfunction syndrome' afflicts a considerable number of depressed elderly patients and may be resistant to conventional pharmacotherapy. Non-pharmacological approaches addressing their behavioral deficits may reduce disability and experienced stress and improve depression. METHODS: This paper focuses on problem solving therapy (PST) because it targets concrete problems that can be understood by patients with executive dysfunction and trains patients to address them using an easy to comprehend structured approach. RESULTS: We suggest that PST is a suitable treatment for patients with the depression-executive dysfunction syndrome because it has been found effective in uncomplicated geriatric major depression and in other psychiatric disorders accompanied by severe executive dysfunction. Furthermore, PST can address specific clinical features of depressed patients with executive dysfunction, especially when modified to address difficulties with affect regulation, initiation and perseveration. CONCLUSIONS: A preliminary study suggests that appropriately modified PST improves problem solving skills, depression and disability in elderly patients with the depression-executive dysfunction syndrome of late life. If these findings are confirmed, PST may become a therapeutic option for a large group of depressed elderly patients likely to be drug resistant.

Alexopoulos GS, Gunning-Dixon FM, Latoussakis V, Kanellopoulos D, Murphy CF. · Weill Cornell Institute of Geriatric Psychiatry, Department Of Psychiatry, Weill Cornell Medical College, New York, USA. · Int J Geriatr Psychiatry. · Pubmed #17979214 No free full text.

Abstract: BACKGROUND: Although several brain abnormalities have been identified in geriatric depression, their relationship to the pathophysiological mechanisms leading to the development and perpetuation of this syndrome remain unclear. METHODS: This paper reviews findings on the anterior cingulate cortex (ACC) function and on the relationship of ACC abnormalities to the clinical presentation and the course of geriatric depression in order to elucidate the pathophysiological role of ACC in this disorder. RESULTS: The ACC is responsible for conflict detection and emotional evaluation of error and is connected to brain structures that regulate mood, emotional valence of thought and autonomic and visceral responses, which are functions disturbed in depression. Geriatric depression often is accompanied by abnormalities in some executive functions and has a clinical presentation consistent with ACC abnormalities. Indices of ACC dysfunction are associated with adverse outcomes of geriatric depression. CONCLUSIONS: Converging findings suggest that at least some ACC functions are abnormal in depression and these abnormalities are pathophysiologically meaningful. Indices of ACC dysfunction may be used to identify subgroups of depressed elderly patients with distinct illness course and treatment needs and serve as the theoretical background for novel treatment development.

Alexopoulos GS, Raue PJ, Sirey JA, Arean PA. · Department of Psychiatry, Weill Cornell Medical College, NY 10605, USA. · Int J Geriatr Psychiatry. · Pubmed #17932995 No free full text.

Abstract: BACKGROUND: Geriatric depression preferentially afflicts individuals with chronic medical illnesses. Disability, hopelessness, lack of acceptance of antidepressant treatment, and limited problem-solving skills contribute to poor treatment adherence, compromised outcomes, and chronically experienced adversity. METHODS: This paper uses depression comorbid with chronic obstructive pulmonary disease (COPD) as a model entity to develop an approach for integrating treatment components essential for improving treatment adherence and outcomes. RESULTS: The behavioral inertia of depression and its coexisting cognitive problems reduce adherence to the sustained and complex demands of the COPD rehabilitation regimen and antidepressant treatment. An intervention identifying reasons for poor treatment adherence and offering direct instructions for addressing them can be combined with problem-solving therapy to target treatment adherence, depressive symptoms, and disability. CONCLUSIONS: An intervention focusing on treatment adherence and problem-solving skills development may serve as the platform for administering specific treatments to address the interacting problems of depressed medically ill patients.

Alexopoulos GS, Schultz SK, Lebowitz BD. · Weill Medical College of Cornell University, White Plains, New York 10605, USA. · Biol Psychiatry. · Pubmed #16026764 No free full text.

Abstract: Geriatric psychiatric syndromes might serve as the starting point for a medical classification of psychiatric disorders, because their medical and neurological comorbidity and their clinical, neuropsychological, and neuroimaging features often reflect specific brain abnormalities. Geriatric syndromes, however, consist of complex behaviors that are unlikely to be caused by single lesions. We propose a model in which aging-related changes in specific brain structures increase the propensity for the development of certain psychiatric syndromes. The predisposing factors are distinct from the mechanisms mediating the expression of a syndromic state, much like hypertension is distinct from stroke, but constitutes a morbid vulnerability. We argue that research seeking to identify both brain abnormalities conferring vulnerability as well as the mediating mechanisms of symptomatology has the potential to lead to a medical classification of psychiatric disorders. In addition, a medical classification can guide the effort to improve treatment and prevention of psychiatric disorders as it can direct therapeutic efforts to the underlying predisposing abnormalities, the syndrome-mediating mechanisms, and to development of behavioral skills needed for coping with adversity and disability.

Alexopoulos GS. · Weill Medical College of Cornell University and Weill-Cornell Institute of Geriatric Psychiatry, 21 Bloomingdale Road, White Plains, New York, NY 10605, USA. · Lancet. · Pubmed #15936426 No free full text.

Abstract: In elderly people, depression mainly affects those with chronic medical illnesses and cognitive impairment, causes suffering, family disruption, and disability, worsens the outcomes of many medical illnesses, and increases mortality. Ageing-related and disease-related processes, including arteriosclerosis and inflammatory, endocrine, and immune changes compromise the integrity of frontostriatal pathways, the amygdala, and the hippocampus, and increase vulnerability to depression. Heredity factors might also play a part. Psychosocial adversity-economic impoverishment, disability, isolation, relocation, caregiving, and bereavement-contributes to physiological changes, further increasing susceptibility to depression or triggering depression in already vulnerable elderly individuals. Treatment with antidepressants is well tolerated by elderly people and is, overall, as effective as in young adults. Evidence-based guidelines for prevention of new episodes of depression are available as are care-delivery systems that increase the likelihood of diagnosis, and improve the treatment of, late-life depression. However, in North America at least, public insurance covers these services inadequately.

Alexopoulos GS, Streim J, Carpenter D, Docherty JP, Anonymous00411. · Cornell Institute of Geriatric Psychiatry and Weill Medical College of Cornell University, USA. · J Clin Psychiatry. · Pubmed #14994733 No free full text.

Abstract: OBJECTIVES: Antipsychotics are widely used in geriatric psychiatric disorders. A growing number of atypical antipsychotics are available, expanding clinical options but complicating decision-making. Many questions about use of antipsychotics in older patients remain unanswered by available clinical literature. We therefore surveyed expert opinion on antipsychotic use in older patients (65 years of age or older) for recommendations concerning indications for antipsychotics, choice of antipsychotics for different conditions (e.g., delirium, dementia, schizophrenia, delusional disorder, psychotic mood disorders) and for patients with comorbid conditions or history of side effects, dosing strategies, duration of treatment, and medication combinations. METHOD: Based on a literature review, a 47-question survey with 1,411 options was developed. Approximately three quarters of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, experts were asked to write in answers. The survey was sent to 52 American experts on treatment of older adults (38 geriatric psychiatrists, 14 geriatric internists/family physicians), 48 (92%) of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Guidelines indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 78% of options rated on the 9-point scale. The experts did not recommend using antipsychotics in panic disorder, generalized anxiety disorder, nonpsychotic major depression, hypochondriasis, neuropathic pain, severe nausea, motion sickness, or irritability, hostility, and sleep disturbance in the absence of a major psychiatric syndrome. However, antipsychotics were favored in several other disorders. For agitated dementia with delusions, the experts' first-line recommendation is an antipsychotic drug alone; they would also consider adding a mood stabilizer. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. There was no first-line recommendation for agitated dementia without delusions; an antipsychotic alone was high second line (rated first line by 60% of the experts). The experts'first-line recommendation for late-life schizophrenia was risperidone (1.25-3.5 mg/day). Quetiapine (100-300 mg/day), olanzapine (7.5-15 mg/day), and aripiprazole (15-30 mg/day) were high second line. For older patients with delusional disorder, an antipsychotic was the only treatment recommended. For agitated nonpsychotic major depression in an older patient, the experts' first-line recommendation was an antidepressant alone (77% first line); second-line options were an antidepressant plus an antipsychotic, electroconvulsive therapy (ECT), an antidepressant plus a benzodiazepine, and an antidepressant plus a mood stabilizer. For nonpsychotic major depression with severe anxiety, the experts recommended an antidepressant alone (79% first line) and would also consider adding a benzodiazepine or mood stabilizer to the antidepressant. If an older patient with adequate dosages for adequate duration, there was limited support for adding an atypical antipsychotic to the antidepressant (36% first line after two failed antidepressant trials). Treatment of choice for geriatric psychotic major depression was an antipsychotic plus an antidepressant (98% first line), with ECT another first-line option (71% first line). For mild geriatric nonpsychotic mania, the first-line recommendation is a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer plus an antipsychotic (57%; first line) or a mood stabilizer alone (48%; first line) and would discontinue any antidepressant the patient is receiving. For psychotic mania, treatment of choice is a mood stabilizer plus an antipsychotic (98%; first line). Risperidone (1.25-3.0 mg/day) and olanzapine (5-15 mg/day) were first-line options in combination with a mood stabilizer for mania with psychosis, with quetiapine (50-250 mg/day) high second line. If a patient has responded well, the experts recommended the following duration of treatment before attempting to taper and discontinue the antipsychotic: delirium, 1 week; agitated dementia, taper within 3-6 months to determine the lowest effective maintenance dose; schizophrenia, indefinite treatment at the lowest effective dose; delusional disorder, 6 months-indefinitely at the lowest effective dose; psychotic major depression, 6 months; and mania with psychosis, 3 months. For patients with diabetes, dyslipidemia, or obesity, the experts would avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency). Quetiapine is first line for a patient with Parkinson's disease. Clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) should be avoided in patients with QTc prolongation or congestive heart failure. For patients with cognitive impairment, constipation, diabetes, diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the experts prefer risperidone, with quetiapine high second line. More than a quarter of the experts considered these combinations contraindicated: clozapine + carbamazepine, ziprasidone + tricyclic antidepressant (TCA), and a low-potency conventional antipsychotic + fluoxetine. In combining antidepressants and antipsychotics, the experts would be much more cautious with selective serotonin reuptake inhibitors that are more potent inhibitors of the CYP 450 enzymes (i.e., fluoxetine, fluvoxamine, paroxetine) and with nefazodone, TCAs, and monoamine oxidase inhibitors. The experts recommended extra monitoring when combining any antipsychotic with lithium, carbamazepine, lamotrigine, or valproate (except aripiprazole, risperidone, or a high-potency conventional plus valproate) or with codeine, phenytoin, or tramadol. CONCLUSIONS: The experts reached a high level of consensus on many of the key treatment questions. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for common clinical dilemmas in the use of antipsychotics in elderly patients. Clinicians should keep in mind that no guidelines can address the complexities of an individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations.

Bartels SJ, Dums AR, Oxman TE, Schneider LS, Areán PA, Alexopoulos GS, Jeste DV. · Department of Psychiatry, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA. · Psychiatr Clin North Am. · Pubmed #14711131 No free full text.

Abstract: At least 20% of people over the age of 65 suffer from mental disorders. It is anticipated that the number of older Americans with psychiatric disorders will double over the next 30 years. There is, however, substantial unmet need. The recent Surgeon General's Report on Mental Health, a Report on Mental Health from the Administration on Aging, and an expert consensus statement underscore the need to plan for the challenge of providing services for elderly people with major mental disorders. Among the greatest challenges is the expertise gap that affects clinicians practicing in routine clinical settings. This gap reflects inadequate training in geriatrics and a failure to incorporate contemporary clinical research findings and known evidence-based practices (EBPs) into usual care. This article provides an overview of the emerging evidence-base supporting the efficacy of empirically-validated geriatric mental health interventions for major geriatric mental health disorders, including systematic EBP reviews, meta-analytic studies, and expert consensus statements. Cautions and limitations regarding the reliance on randomized, controlled trials, meta-analyses, and systematic reviews also are presented.

Alexopoulos GS. · Weill-Cornell Institute of Geriatric Psychiatry, Weill Medical College of Cornell University, White Plains, NY 10605, USA. · J Clin Psychiatry. · Pubmed #14658931 No free full text.

Abstract: Late-onset depression has been conceptualized as a neurologic disease. This view has been supported by studies suggesting that late-onset depression is associated with cognitive impairment and neurologic comorbidity that may or may not be clinically evident when depression is first diagnosed. Findings implicating a dysfunction of frontostriatal-limbic pathways in geriatric depression have led to the depression-executive dysfunction (DED) syndrome hypothesis. Subsequent studies suggested that DED has slow, poor, or abnormal response to classical antidepressants. DED is characterized by psychomotor retardation, reduced interest in activities, impaired insight and pronounced behavioral disability. This clinical presentation begs the question whether agents that can selectively activate internal vigilance and therefore improve alertness have beneficial effects on DED. There is early evidence that psychosocial interventions aimed at improving the behavioral deficits of DED patients may also be effective in increasing remission rates and reducing depressive symptoms and disability.

Charney DS, Reynolds CF, Lewis L, Lebowitz BD, Sunderland T, Alexopoulos GS, Blazer DG, Katz IR, Meyers BS, Arean PA, Borson S, Brown C, Bruce ML, Callahan CM, Charlson ME, Conwell Y, Cuthbert BN, Devanand DP, Gibson MJ, Gottlieb GL, Krishnan KR, Laden SK, Lyketsos CG, Mulsant BH, Niederehe G, Olin JT, Oslin DW, Pearson J, Persky T, Pollock BG, Raetzman S, Reynolds M, Salzman C, Schulz R, Schwenk TL, Scolnick E, Unutzer J, Weissman MM, Young RC, Anonymous00321. · National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. · Arch Gen Psychiatry. · Pubmed #12860770 No free full text.

Abstract: 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.

Alexopoulos GS. · Weill Medical College of Cornell University, White Plains, NY 10605, USA. · Am J Geriatr Psychiatry. · Pubmed #12427577 No free full text.

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

Bartels SJ, Dums AR, Oxman TE, Schneider LS, Areán PA, Alexopoulos GS, Jeste DV. · Department of Psychiatry, Dartmouth Medical School, Hannover, New Hampshire, USA. · Psychiatr Serv. · Pubmed #12407270 links to  free full text

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

Alexopoulos GS, Buckwalter K, Olin J, Martinez R, Wainscott C, Krishnan KR. · Weill Medical College of Cornell University, Cornell Institute of Geriatric Psychiatry, White Plains, New York 10605, USA. · Biol Psychiatry. · Pubmed #12361668 No free full text.

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

Alexopoulos GS, Borson S, Cuthbert BN, Devanand DP, Mulsant BH, Olin JT, Oslin DW. · Weil Medical College, Cornell University (GSA), White Plains, New York 10605, USA. · Biol Psychiatry. · Pubmed #12182923 No free full text.

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

Szanto K, Gildengers A, Mulsant BH, Brown G, Alexopoulos GS, Reynolds CF. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. · Drugs Aging. · Pubmed #11929324 No free full text.

Abstract: In almost all industrialised countries, men aged 75 years and older have the highest suicide rate among all age groups. Although in younger age groups suicide attempts are often impulsive and communicative acts, suicide attempts in older people (defined as aged 65 years and older) are often long planned and involve high-lethality methods. These characteristics, in addition to the fact that elderly are more fragile and frequently live alone, more often lead to fatal outcome. In later life, in both sexes, the most common diagnosis in those who attempt or complete suicide is major depression. In contrast to other age groups, comorbidity with substance abuse and personality disorders is less frequent. Physical illness plays an important role in the suicidal behaviour of the elderly: most frequently, depression and illness co-occur; less often, the physical illness or the treating medications are causally related to the depressive symptoms. However, only 2 to 4% of terminally ill elderly commit suicide. In addition to physical illness, complicated or traumatic grief, anxiety, unremitting hopelessness after recovery from a depressive episode and history of previous suicide attempts are risk factors for suicide attempts and completed suicide. During a depressive episode, elderly patients with suicidal ideation have higher levels of anxiety and, during treatment, anxiety decreases the probability of remission and recovery. As well as overt suicide attempts, indirect self-destructive behaviours, which often lead to premature death, are common, especially in residents of nursing homes, where more immediate means to commit suicide are restricted. Although we do not have randomised trials of treatment, studies suggest that antidepressant treatment may decrease suicide risk. Prevention and treatment trials are underway to detect the effectiveness of improved treatment of depression by primary care physicians as a means of reducing the prevalence of depressive symptoms, hopelessness and suicidal ideation.

Lenze EJ, Mulsant BH, Shear MK, Alexopoulos GS, Frank E, Reynolds CF. · Intervention Research Centers in Late-Life Mood Disorders, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. · Depress Anxiety. · Pubmed #11668661 No free full text.

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

Reynolds CF, Alexopoulos GS, Katz IR, Lebowitz BD. · Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. · Drugs Aging. · Pubmed #11482744 No free full text.

Abstract: Depression in old age frequently follows a chronic and/or relapsing course, related to medical comorbidity, cognitive impairment and depletion of psychosocial resources. As endorsed by the US National Institutes of Health (NIH) Consensus Development Conference on the Diagnosis and Treatment of Late Life Depression, a major goal of treatment is to prevent relapse, recurrence and chronicity. We believe that most, if not all, elderly patients with major depressive episodes are appropriate candidates for maintenance therapy, because of the vulnerability to relapse and recurrence and because of the favourable benefit to risk ratio of available treatments. Antidepressant pharmacotherapy is the mainstay of this therapeutic goal, but psychosocial approaches (especially interpersonal psychotherapy) have also been shown to contribute significantly to prevention of a chronic depressive illness and to prevention of the disability that attends depression. Studies published to date have established the long term or maintenance efficacy of the tricyclic antidepressant nortriptyline. Current, ongoing studies are addressing the maintenance efficacy of paroxetine and citalopram to prolong recovery in depression associated with old age. These studies are focusing particularly on patients aged 70 years and above, who are at high risk of recurrence, and on patients in primary care settings, where under-recognition and under-treatment of depression in the elderly have been costly from a public health perspective in terms of increased medical utilisation, burden to patients and families, and high rates of suicide. Depression in old age is a major contributor to the global burden of illness-related disability, but it is extremely treatable if appropriate pharmacotherapy is prescribed and accepted by patients and their caregivers.

Klausner EJ, Alexopoulos GS. · Department of Psychiatry at the Joan and Sanford I. Weill Medical College of Cornell University and the New York Hospital-Cornell Medical Center, Westchester Division, USA. · Psychiatr Serv. · Pubmed #10478907 links to  free full text

Abstract: 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.