Suicidal thinking and behavior during treatment with sertraline in late-life depression.

OBJECTIVE: To determine effects of sertraline on suicidal thinking and behavior in patients with late-life major depression. METHODS: This was a secondary analysis of an eight-week, placebo-controlled, double-blind randomized trial of a multicenter trial at 66 clinical sites. Outpatients >/=60 years of age with major depression and a Hamilton Depression Rating (HAMD) score >/=18 were included. Intervention was sertraline 50-100 mg/day or placebo for eight weeks. Measurements were 17-item HAMD administered at baseline and two-week intervals. HAMD Item 3 used to assess suicidal ideation (SI) and behavior. Reports of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, and spontaneously reported adverse events reviewed. RESULTS: A total of 747 patients received at least one dose of medication, and 728 had at least one posttreatment assessment. Mean age (+/-SD) was 69.8 +/- 6.7 years (range: 59-97 years) and 56% were female. There were no completed suicides or suicide attempts during the double-blind trial. One SAE, hospitalization, was associated with SI in a patient on sertraline. No other AEs were associated with SI or behavior. HAMD Item 3 ratings progressively declined during the trial with significantly lower values for sertraline than placebo (Z = 2.41, p <0.02). In 248 patients with HAMD Item 3 of zero at baseline, the percentage of patients whose Item 3 ratings increased during treatment did not differ in the two groups (22.4% versus 25.8% for sertraline and placebo, respectively.) CONCLUSION: Sertraline was associated with significantly lower HAMD Item 3 scores than placebo during treatment. There was no evidence of greater emergent suicidal thinking or behavior with sertraline than placebo.     

Risk factors for falls during treatment of late-life depression

BACKGROUND: Prior studies have found that antidepressant medications are associated with an increased risk of falling in elderly persons. However, little is known about the prevention of falls during treatment for depression in elderly persons. This study evaluated the time course and potential risk factors for falls in a treatment protocol for late-life depression to identify specific at-risk periods and risk factors for falls in this population. METHOD: One hundred four subjects aged 69 years and over were treated in a protocolized manner using paroxetine and interpersonal psychotherapy. Those who did not respond received augmentation therapy with bupropion, nortriptyline, or lithium. Subjects were assessed at baseline and weekly during treatment; demographic and clinical characteristics of those who experienced a fall during treatment were compared with those who did not fall. Cox proportional hazards models were used to define risk factors for falls in univariate and multivariate models. RESULTS: During a mean of 21 weeks of treatment, 40 subjects (38%) fell. About half (53%) of the subjects fell during the first 6 weeks of treatment. In the multivariate model, memory impairment and orthostatic changes in blood pressure during treatment were risk factors for falling. Additionally, augmentation with bupropion appeared to be a risk factor for falls in univariate analysis, but this result is preliminary due to the small number of subjects who took bupropion. CONCLUSION: Increased monitoring for falls is warranted during the acute treatment of late-life depression. When treating such patients, clinicians should be especially watchful of those with memory impairments or those who develop orthostatic blood pressure changes; orthostatic blood pressure should be measured throughout acute treatment. Additionally, augmenting paroxetine with bupropion may also increase the risk of falls, and this medication combination should be used with caution in elderly patients.     

Day-clinic treatment of late-life depression

BACKGROUND: There are few studies evaluating treatment in gerontopsychiatric day-clinics. In this paper, data are presented on the outcome of day-clinic treatment in late-life depression. METHOD: Forty-four depressed elderly patients (mean Hamilton Depression Score: 17.6) were examined at admission and discharge for psychopathology, functioning in daily living, social situation, burden with medical disease and quality of life. RESULTS: At discharge, the patients showed a significant reduction in depressive symptoms, improvements in cognitive performance, social activities and contacts. However, a more detailed analysis revealed that only patients responding to treatment (n=20) improved in the respective parameters. Patients, who did not recover fully from depression (n=24), did not improve in any of these parameters. At admission, responders and nonresponders did not differ concerning quality of life. At discharge, responders were significantly more satisfied in 11 of 20 domains of life quality. A shorter life time duration of depressive disease and male sex were predictive for a remission of depression. Thus, it could be shown that a considerable number of patients suffering from late-life depression may be successfully treated in a gerontopsychiatric day-clinic and 45.5% fully recover from depression. CONCLUSIONS: The day-clinic setting meets the specific needs of patients suffering from late-life depression by maintaining them in the community, supporting their abilities for self-care and promoting social contacts. Treatment in a day-clinic may be recommended for many elderly depressed patients.     

Occurrence and course of suicidality during short-term treatment of late-life depression

BACKGROUND: Elderly persons (> or =65 years) have the highest rate of suicide; still, little is known about the occurrence, course, and responsivity of suicidal ideation during treatment of depression in late life and how suicidality affects treatment response. METHODS: This study was undertaken to determine (1) how suicidal ideation changes during short-term depression treatment and (2) whether treatment response differs among 3 groups of patients based on their levels of suicidality at baseline and during treatment (those with a recent suicide attempt or current suicidal ideation [high-risk group; n = 46], those with recurrent thoughts of death [moderate-risk group; n = 143], or those with no suicide attempt, suicidal ideation, or thoughts of death [low-risk group; n = 206]). This is a secondary analysis of pooled data from 3 treatment studies of late-life major depression. Participants were 395 elderly persons with a current major depressive episode, treated as inpatients or outpatients under protocolized conditions with paroxetine hydrochloride or nortriptyline hydrochloride, with or without interpersonal psychotherapy. Changes in suicidal ideation over time, rate of responses, and time to response in each group were compared. RESULTS: Suicidal ideation decreased rapidly early in the course of treatment, with more gradual change thereafter. At the beginning of treatment, 77.5% of the patients reported suicidal ideation, thoughts of death, or feelings that life is empty. After 12 weeks of treatment, suicidal ideation had resolved in all treated patients; 4.6% still reported thoughts of death. However, 6-week (P =.001) and 12-week (P =.02) rates of response were significantly lower in high-risk patients than in low- and moderate-risk patients. High- and moderate-risk patients needed a significantly (P<.001) longer time to respond than low-risk patients (median time to response, 6 and 5 vs 3 weeks). CONCLUSIONS: While suicidal ideation resolves rapidly, the resolution of thoughts about death is more gradual. Suicidal elderly persons with depression require special attention during depression treatment because they have a lower response rate and need a longer time to respond.     

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.     

老年期抑郁障碍的临床诊治

随着老龄化进程的加快和社会生活方式的转变,老年期抑郁障碍（LLD）的患病率逐年增高。作为最常见的老年期精神障碍,LLD严重影响患者的生活质量,并给家庭和社会带来沉重负担,甚至可能威胁老年患者的生命安全。LLD的发病机制尚不明确,可能是生物、社会和心理多方面因素共同作用所致。由于老年群体的机体功能衰退、共病躯体疾病较多,故对LLD患者的诊治与处理年轻的成年抑郁障碍患者会有所不同。本文对LLD相关的流行病学特征、临床评估和诊断、共病情况以及治疗与干预等方面进行梳理,并着重介绍LLD的药物治疗,以期为临床对LLD的优化诊治和改善预后提供参考。     

Cerebrovascular disease and late-life depression.

Depression may occur as a result of vascular disease in a significant subpopulation of elderly persons. Indirect support for vascular disease as an underlying etiology of late-life depression includes the high rate of depression in patients with vascular disease, the frequency of "silent stroke" and white-matter hyperintensities in late-life depression, and the lower frequency of positive family histories of depression in such patients. The authors evaluate the associations of late-life depression with cerebrovascular disease by reviewing the existing pathophysiological, prognosis, and treatment-outcomes studies. Findings are based on review of the current literature systematically searched in electronic databases. Review of such studies indicates a high frequency of depression in older patients with cardiovascular and cerebrovascular diseases, and the possibility of a bidirectional relationship between depression and vascular disease. Studies examining patients with vascular depression have found that such patients have different symptom profiles, greater disability, and higher risk for poorer outcomes than those with nonvascular depression. Since the vascular depression hypothesis was proposed as a conceptual framework, evidence has accumulated that patients with vascular depression may have poorer outcomes that may be related in part to executive dysfunction and consequent disability. However, the association of vascular risk factors with geriatric depression has not been consistent in the studies to-date. Although an association between a subset of late-life depression and vascular disease is clear, significant gaps remain in our understanding. Further research is needed to establish the precise linkages and interactions between vascular disease and geriatric depression.     

老年抑郁症治疗现状

随着人口老龄化,老年抑郁症已经成为影响老年人身心健康的重要疾病,应予以重视。 老年抑郁症的诊断不明确,其发病机制、临床表现、治疗、转归与其他类型抑郁症有很大差异。近年来, 关于老年抑郁治疗的相关文献日益增加,但结论并不一致。基于上述问题,现将关于老年抑郁症治疗 的相关文献进行阐述,旨为临床工作以及未来的研究提供思路与参考。     

Thought suppression and treatment outcome in late-life depression

This study examined severity of depression, age of onset, and thought suppression as predictors of treatment outcome. Measures were taken pre-treatment, post-treatment, and at six-month follow-up in 34 depressed older adults receiving the treatment protocol described in Lynch, Morse, Mendelson & Robins (Dialectical behavior therapy for depressed older adults, American Journal of Geriatric Psychiatry, 11, 33-45, 2003). Severity and chronicity of depression and higher levels of thought suppression were associated with higher depressive symptoms six months after treatment. Findings are consistent with research suggesting that severity and chronicity of depression predict poor clinical outcome. In addition, these results provide preliminary evidence that the tendency to cope with unwanted thoughts by deliberate attempts to not experience such thoughts may be an important pre-treatment predictor of outcome among depressed older adults. Larger studies are needed to explore whether thought suppression mediates long-term recovery from depression.     

Cytokines and late-life depression

Cytokines are peripherally and centrally produced proteins that regulate immune and immunological responses. They also have neurochemical, neuroendocrine and behavioural effects similar to those seen in patients with depression. A review of the literature reveals several cytokines, including IL-1beta, IL-2, IL-6 and IFN, have been shown to be elevated in plasma of working-age adults with depression and dysthymia. A more detailed review of the literature also reveals similar associations between cytokines and late-life depression, with IL-1beta, IL-6 and TNF-alpha all being reported to be elevated in both depression and dysthymia. It has been hypothesized that cytokines provide the link between depression, neurochemical changes and the altered HPA axis that are known to occur in this disease, and evidence is presented that supports this view. However, the evidence that antidepressants may have effects on cytokines is conflicting. Increased cytokine levels may also serve as an explanation for the increased risk for vascular disease that has been associated with depression, and a possible mechanism for this is discussed.     

Vascular nutritional correlates of late-life depression.

OBJECTIVE: The authors sought to examine the association of vascular nutritional factors and depression in an elderly cohort of depression (currently and recently depressed) and comparison (never depressed) subjects. METHOD: Nutrient intake over the past year was assessed in 196 elderly depression and comparison individuals with a Block 1998 food-frequency questionnaire. Nutrient intake, body mass index, and Keys score (a measure of the serum cholesterol-raising capacity of the diet) were determined. Subjects were age 60 and over and were participants in a longitudinal study of major depression. All subjects received psychiatric and medical comorbidity assessments; depression subjects also received psychiatric treatment. RESULTS: Vascular nutritional factors differed between depression and comparison subjects. The depression group had higher intake of saturated fat and cholesterol, higher body mass indices, lower alcohol intake, and higher Keys score than the comparison group. After controlling for age, sex, education, race, and medical comorbidity, associations remained for cholesterol, alcohol, and Keys score. Depression was found to be associated with overall dietary pattern as defined by total kilocalories, saturated fat, cholesterol, body mass index, polyunsaturated fat, sodium, and alcohol. CONCLUSIONS: This study provides evidence that dietary vascular risk factors differ in individuals with current or prior depression when compared with individuals with no history of depression.     

Psychotic late-life depression: a 376-case study.

The aim of the report was to study clinical differences between psychotic late-life depression and psychotic depression in younger patients, to determine if differences were age-related or specific for psychotic late-life depression. Three hundred seventy-six consecutive outpatients, presenting for treatment of unipolar or bipolar depression (with or without psychotic features), were assessed by means of the Structured Clinical Interview for DSM-IV, the Montgomery and Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. Results showed that psychotic late-life (50 years or more) depression, versus psychotic depression in younger patients, was associated with significantly higher age at study entry/onset, longer duration, and lower comorbidity. Psychotic depression versus nonpsychotic late-life depression, in late-life and in younger patients, was associated with significantly greater severity, lower comorbidity, more patients with bipolar I disorder, and fewer patients with unipolar disorder. Findings were related to psychosis or to age, and not to specific features of psychotic late-life depression. These results support a unitary view of psychotic depression.     

Cardiovascular changes associated with venlafaxine in the treatment of late-life depression.

BACKGROUND: Potential cardiovascular side effects from venlafaxine-XR must be considered when prescribing this medication, especially in geriatric patients, who often present with comorbid medical conditions. METHODS: Participants age 60 and older with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of a major depressive episode without psychotic features were treated openly with venlafaxine-XR for 12 weeks during which venlafaxine-XR was titrated based on tolerability and response according to predefined guidelines. Sitting and standing blood pressures and heart rates were measured. A 12-lead electrocardiogram was obtained at baseline and at week 12. RESULTS: Sixty-two participants started treatment; 59 completed at least two weeks of the 12-week study. The mean final dose of venlafaxine-XR was 195.5 mg/day (standard deviation: 72.2). Twenty-four percent (95% confidence interval [CI]: 7.3%-40.7%) of initially normotensive participants and 54% (95% CI: 34.3%-74%) of those with preexisting hypertension experienced an increase in blood pressure. Twenty-nine percent (95% CI: 14.6%-43.4%) of participants developed orthostatic hypotension. Two participants experienced a clinically significant increase in QTc interval. One participant reported new-onset mild dizziness, whereas four participants reported new-onset tachycardia or palpitation. Overall, 17 unique participants (28.8%; 95% CI: 17.3%-40.4%) experienced a new-onset cardiovascular problem, potentially related to the study medication. CONCLUSION: Overall, venlafaxine-XR was well tolerated. However, similar to previous reports, venlafaxine-XR was associated with some undesirable cardiovascular effects in some of the participants. Systematic monitoring of cardiovascular parameters during treatment with venlafaxine-XR should be strongly recommended, especially in the elderly.     

Cost-effectiveness of improving primary care treatment of late-life depression

CONTEXT: Depression is a leading cause of functional impairment in elderly individuals and is associated with high medical costs, but there are large gaps in quality of treatment in primary care. OBJECTIVE: To determine the incremental cost-effectiveness of the Improving Mood Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. DESIGN: Randomized controlled trial with recruitment from July 1999 to August 2001. SETTING: Eighteen primary care clinics from 8 health care organizations in 5 states. PARTICIPANTS: A total of 1801 patients 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). INTERVENTION: Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual primary care (n = 895). Intervention patients were provided access to a depression care manager supervised by a psychiatrist and primary care physician. Depression care managers offered education, support of antidepressant medications prescribed in primary care, and problem-solving treatment in primary care (a brief psychotherapy). MAIN OUTCOME MEASURES: Total outpatient costs, depression-free days, and quality-adjusted life-years. RESULTS: Relative to usual care, intervention patients experienced 107 (95% confidence interval [CI], 86 to 128) more depression-free days over 24 months. Total outpatient costs were USD $295 (95% CI, -$525 to $1115) higher during this period. The incremental outpatient cost per depression-free day was USD $2.76 (95% CI, -$4.95 to $10.47) and incremental outpatient costs per quality-adjusted life-year ranged from USD $2519 (95% CI, -$4517 to $9554) to USD $5037 (95% CI, -$9034 to $19 108). Results of a bootstrap analysis suggested a 25% probability that the IMPACT intervention was "dominant" (ie, lower costs and greater effectiveness). CONCLUSIONS: The IMPACT intervention is a high-value investment for older adults; it is associated with high clinical benefits at a low increment in health care costs.     

Frontostriatal and limbic dysfunction in late-life depression.

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

Changes in cognitive functioning following treatment of late-life depression

OBJECTIVE: Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression. METHOD: Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment. RESULTS: As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains. CONCLUSIONS: Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.     

Apolipoprotein-E and white-matter hyperintensities in late-life depression.

The authors conducted a follow-up study of 16 patients with late-life depression approximately 6 years after their initial assessment to evaluate the relationships between apolipoprotein-E (APO-E) status and white-matter hyperintensities (WMH). Ten patients had WMH at baseline, and four patients demonstrated an increase in WMH size over time. Three of four patients with the APO-E epsilon 4 allele demonstrated an increase in WMH over time, and only 1 of 12 patients without an epsilon 4 allele had an increase in WMH. Three of four patients with APO-E epsilon 4 allele developed a chronic course of major depression at follow-up. Patients with APO-E epsilon 4 had a higher number of depressive episodes and lower age at onset. APO-E may be a risk factor for cerebrovascular disease associated with late-life depression and may affect the clinical characteristics and disease course of depression.