Treatment of depression in late life

This paper updates the 1996 review of treatment approaches published in the Am J Geriatr Psychiatry (1996;4[suppl 1]:S51-S65 [see ref33]) and a chapter in A Guide to Treatments that Work (Nathan PE, Gorman JM, eds), Oxford University Press, New York, 1998 [see ref 54]:. The major focus is on psychophannacoiogy with attention also to the évidence for the efficacy of psychotherapeutic and somatic approaches.     

Assessment of late life depression.

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.     

Biological risk factors in late life depression.

A number of biological risk factors have been tentatively identified for unipolar and bipolar disorder in the elderly. The list includes genetic factors as well as medical illness in general and vascular disease in particular. Most of these risk factors have been identified on the basis of cross sectional studies rather than longitudinal studies. There is a need for long term epidemiologic and prevention studies (in the case of modifiable risk factors). The modifiable risk factors include medical illness in general and vascular disease in particular. An example is the use of antidepressants following stroke to prevent the onset of depression. Of particular interest is the role of vascular risk factors and MRI changes suggesting subtle cerebrovascular disease in the development of depression and bipolar disorder in late life. The changes have been established using both clinical samples and in the case of depression in cross sectional epidemiologic samples. The location of these cerebrovascular changes has contributed to our understanding of the regions of the brain implicated in the pathophysiology of depression. Further longitudinal and preventive studies are needed to conclusively demonstrate these as biological risk factors.     

Comorbid psychiatric disorders in late life depression.

In late life depression, common comorbid psychiatric disorders are alcohol use, anxiety, and personality disorders. Elderly depressed patients are three to four times more likely to have an alcohol use disorder compared with nondepressed elderly subjects, with a prevalence of 15%-30% in patients with late life major depression. While the presence of a comorbid alcohol use disorder may worsen the prognosis for geriatric depression, limited data suggest that successful treatment of depression combined with reducing alcohol use leads to the best possible outcomes. Most studies show that the overall prevalence of anxiety disorders, particularly panic disorder and obsessive-compulsive disorder, is low in geriatric depression, but generalized anxiety disorder may not be uncommon. It remains unclear if the presence of a comorbid anxiety disorder impacts on the treatment and prognosis of late life major depression. Personality disorders occur in 10%-30% of patients with late life major depression or dysthymic disorder, particularly in patients with early onset depressive illness. Cluster C disorders, including the avoidant, dependent, and obsessive-compulsive subtypes predominate, while Cluster B diagnoses, including borderline, narcissistic, histrionic and antisocial, are rare. Overall, the research database on comorbid psychiatric disorders in major and nonmajor late life depression is relatively sparse. Since comorbid psychiatric disorders affect clinical course and prognosis, and may worsen long-term disability in late life depression, considerably more research in this field is needed.     

Treatment-resistant depression in adolescents: recognition and management

Approximately 20% of adolescents experience at least one depressive episode by the time they enter their adult years. For most adolescents, depression, although serious, either remits spontaneously or responds to treatment. For a smaller but significant proportion of adolescents, however, depression can be long-lasting and relatively unresponsive to initial treatment. In this article the authors provide an operational definition of treatment-resistant depression, identify factors associated with treatment nonresponse, describe an approach to the management of treatment-resistant depression, and advance suggestions for promising avenues of research.     

难治性抑郁症及其诊断治疗

本文目的是探讨难治性抑郁症(TRD),尤其是不同治疗策略及其选择.尽管抗抑郁药物的疗效已十分确切,但临床中仍有20％～30％的抑郁症患者经抗抑郁药规范治疗后无效或效果不佳,TRD治疗成本更高,疾病负担更重.本文从定义、患病率、疾病负担、病因学机制、危险因素、评估分级、鉴别诊断以及治疗等方面展开探讨,重点阐述不同治疗策略...     

Treatment-resistant depression: critique of current approaches

The aim of the present study was to critically appraise current conceptual approaches; demographic, neurobiological and clinical correlates; and management strategies of treatment-resistant depression (TRD), especially in light of recent research findings. To this end, a review of the relevant English-language literature was undertaken using Medline, Embase and Psychinfo. TRD has been defined in conceptually restrictive terms as symptomatic non-response to physical therapies alone, with little systematic study of aetiology made. It is likely that a range of sociodemographic (such as higher socioeconomic status), genetic (such as variation in functional monoamine polymorphisms) and clinical variables (such as signal hyperintensities seen on structural neuroimaging scans) are responsible for non-response in individuals. There is insufficient evidence to suggest that TRD is associated with specific subtypes of depression, physical comorbidity, personality or chronicity. The large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and other studies have suggested that a structured psychotherapy such as cognitive behaviour therapy may be as effective as medication in initial drug non-responders. Also conventional alternatives such as the use of older antidepressant classes, pharmacological augmentation or electroconvulsive therapy in established cases of TRD are not as effective as traditionally thought. There is insufficient preliminary evidence to make formal recommendations about the use of novel brain stimulation techniques in TRD. TRD should be re-defined as the failure to reach symptomatic and functional remission after adequate treatment with physical and psychological therapies. Treatment resistance may be more usefully conceived within the context of well-defined cohorts such as patients with specific subtypes of depression. Although neurobiological markers such as gene polymorphisms, which are potentially predictive of medication tolerance and efficacy, may be used in the future, it is likely that sociocultural variables such as beliefs about depression, and evidence-based treatments for it, will also determine treatment resistance.     

老年抑郁症的临床现象学特征

目的：探讨老年抑郁症的临床现象学特征。方法：按中国精神障碍分类与诊断标准第3版心境障碍抑郁发作诊断标准，收集33例60岁以上首次发作的患者(老年组)，30例18—50岁首次发作的患者(青壮年组)进行对照研究。结果：老年组焦虑、激越、疑病、记忆减退、胃肠症状和伴发躯体疾病明显多于青壮年组，焦虑程度较青壮年组严重。老年组近期疗效比青壮年组差。结论：老年抑郁症症状特征及预后各方面均有自身的特点。     

Structural differentiation of self-reported depression and anxiety in late life

Research has shown impressive support for tripartite models of anxiety and depression that include a common factor of negative affect, and the unique factors positive affect and arousal. It is not clear whether this structure extends into later life. The current study used confirmatory factor analysis to model the structural relationship of anxiety and depression in two samples of older adults: a large probability sample (N = 1429) and a smaller convenience sample (N = 210). Across all analyses, a correlated, two-factor, psychometric model was most parsimonious. The tripartite model could be fit to the data, but added no explanatory power; in some cases a one-factor model also fit. The results suggest that there is a unitary factor of "distress" that incorporates anxiety and depression, but that the structure is not consistent with factor structures found in younger samples. Instead, the broad constructs may be represented in a more complex manner among older adults, and are less easily differentiated.     

Acute open-trial nortriptyline therapy of bereavement-related depression in late life

BACKGROUND: The aim of this study was to generate preliminary data on the clinical efficacy of nortriptyline in bereavement-related depression in late life. METHODS: Data are presented on 13 patients (5 men, 8 women), ranging in age from 61 to 78 years (mean = 71.1). Mean time from spousal loss to the beginning of treatment was 11.9 months (range 2-25). Subjects were required to meet Research Diagnostic Criteria for syndromal current major depression and to have a stable Hamilton Rating Scale for Depression (HAM-D) score of greater than or equal to 15. Ten of the 13 volunteers were experiencing their first lifetime episode of major depression. Patients were treated with nortriptyline (mean dose = 49.2 mg/day; mean steady-state level = 68.1 ng/mL). Ratings performed at base-line and weekly during therapy were used to assess symptomatology, intensity of grief, level of functioning, social support, physical impairment, and medication side effects. RESULTS: Pretreatment HAM-D ratings average 22.1 +/- 3.6; posttreatment, 7.2 +/- 2.8, representing a 67.9% decrease. All other rating scales showed significant clinical improvement, except the Texas Revised Inventory of Grief (a measure of grief intensity) (pretreatment, 51.4 +/- 7.3; posttreatment, 46.6 +/- 6.9, only a 9.3% decrease). Conclusions: These results suggest that nortriptyline is associated with significant symptomatic improvement in all areas of bereavement-related depression except continued intensity of grief after a median treatment interval of 6.4 weeks. This study indicates the need for a controlled clinical trial to determine the placebo response rate, the relapse rate after discontinuation of medication, and the value of combination therapy (using both pharmacotherapy and psychotherapy).     

Impacting late life depression: integrating a depression intervention into primary care

Care for depression in late life is often less successful in primary care than in carefully controlled clinical trials. Collaborative care models attempt to integrate mental health services into primary care. The authors conducted two focus groups and semi-structured individual interviews with all Depression Clinical Specialists (DCSs) working with Project IMPACT (Improving Mood: Promoting Access to Collaborative Treatment), a study testing a collaborative care intervention for late life depression, to examine integration of the intervention model into primary care. DCSs described key intervention components, including supervision from a psychiatrist and a liaison primary care provider, weekly team meetings, computerized patient tracking, and outcomes assessment tools as effective in supporting patient care. DCSs discussed details of protocols, training, environmental set-up, and interpersonal factors that seemed to facilitate integration. DCSs also identified research-related factors that may need to be preserved in the real world. Basic elements of the IMPACT model seem to support integration of late life depression care into primary care. Research-related components may need modification for dissemination.     

Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression

Background

Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions.

Methods

MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls.

Results

When comparing the three groups and adjusting for age, the Mini‐Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls.

Conclusions

In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuranatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.Reduced hippocampal volume in late life depression (depression in those aged ⩾60 years) is associated with a chronic intermittent illness course.^1,2,3,4 Accordingly, older patients with recurrent early onset depression (EOD, first onset of depression before 60 years) would therefore have smaller hippocampal volumes compared with patients with late onset depression (LOD, first onset of depression at age 60 years or after) because of the longer duration of the disease. However, two recent studies showed smaller hippocampal volumes in patients with LOD compared with those with EOD.^5,6The latter observation could have been confounded by the increased prevalence of subcortical white matter lesions among patients with LOD^7,8,9 as these lesions may be related to hippocampal atrophy.^10,11,12 Therefore, in the current study we wished to investigate the relationship between age of onset of depression and hippocampal volume, with adjustment for subcortical white matter lesions, in elderly (⩾60 years) patients with chronic recurrent EOD and patients with LOD.     

Self-efficacy and depression in late life: a primary prevention proposal

Feelings of sadness and loneliness are ubiquitous in late life and a risk factor for depression and perhaps other mental illnesses in late life. Targeting sadness and loneliness for an intervention addresses both primary risk reduction for depressive disorders and promotion of overall mental health in the elderly. Nevertheless, few studies document the efficacy of primary prevention efforts in preventing depressive disorders in the elderly. The author argues that the attainment of positive mental health depends in considerable part upon an individual's self-efficacy--the belief that one can organize and execute the courses of action required to develop and enhance a person's belief that he or she can act in ways that lead to a desired goal. Self-efficacy is strengthened, not by some general or abstract instruction, but rather by the experience of successfully dealing with and thus overcoming specific problems. The extant literature suggests that many potential approaches may be available to develop and enhance self-efficacy in the elderly--approaches that potentially could be broadly applicable in community settings.