Efficacy of treatment in older depressed patients: a systematic review and meta-analysis of double-blind randomized controlled trials with antidepressants.

BACKGROUND: This systematic review evaluated all published double-blind, randomized controlled antidepressant trials (RCTs) of acute phase treatment of older depressed patients. METHODS: Meta-analyses were conducted in 51 double-blind RCTs of antidepressants in older patients. The results were also compared with 29 double-blind RCTs that did not produce extractable data to enter the meta-analysis. RESULTS: All classes of antidepressant (TCA's, SSRIs and other antidepressants) were more effective than placebo in achieving response. In achieving remission however, only pooling all 3 classes of antidepressants together showed a statistically significant difference from placebo. No differences were found in remission or response rates between classes of antidepressants. TCAs were also equally effective compared with SSRIs in achieving response in more severely depressed patients. The numbers needed to treat (NNT) were 14.4 (95% CI 8.3-50) for one additional remission to antidepressants compared with placebo and 6.7 (95% CI 4.8-10) for response. The results of the double-blind RCTs that did not produce extractable data to enter the meta-analysis were in concordance with the RCTs that were included in the meta-analysis. LIMITATIONS: Only 4 RCTs were found that have not been published. Few studies have focused on severely depressed older people. CONCLUSIONS: Antidepressant treatment in older depressed patients is efficacious. We could not demonstrate differences in effectiveness between different classes of antidepressants; this was also the case in more severely depressed patients.

Continuing treatment of depression in the elderly: a systematic review and meta-analysis of double-blinded randomized controlled trials with antidepressants.

OBJECTIVE: To establish the efficacy and tolerability of continuing treatment with antidepressants in preventing relapses and recurrences in elderly depressed patients and to analyze differences between tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). DESIGN: The authors conducted a systematic literature search to identify all randomized, placebo-controlled, double-blinded clinical trials(RCTs) in elderly patients. Data were pooled from eight double-blinded RCTs of continuation and maintenance treatment in the elderly with 925 participating patients. RESULTS: The number of patients needed to treat (NNT) for antidepressants to prevent one additional relapse or recurrence was 3 6 (95% confidence interval [CI]: 2.8-4.8).The NNT for TCAs was 2.9 (95% CI: 2.2-4.6), compared with a NNT for SSRIs of 4.2(95% CI: 3.2-5.9). In the five studies that provide drop out data, 14 of 330 patients(4.2%) using an antidepressant dropped out due to side effects compared with 17 of 330 patients (5.2%) using a placebo (χ² = 0.305, df = 1, p = 0.581). Tolerability did not differ between TCAs and SSRIs. CONCLUSION: Continuing treatment with antidepressants in elderly patients is efficacious compared with placebo in preventing relapses and recurrences. Efficacy and tolerability during long-term treatment does not differ between TCAs and SSRIs.

Emotional and informational patient cues: the impact of nurses' responses on recall.

OBJECTIVE: To investigate older cancer patients' informational and emotional cues, how nurses respond to these cues and the effect of cues and responses on patients' information recall. METHODS: 105 cancer patients (aged >or=65 years) completed a recall questionnaire after an educational session preceding chemotherapy treatment. Recall was checked against the actual communication in videorecordings of the consultations. Patients' emotional and informational cues and subsequent responses by the nurse were rated using an adaptation of the Medical Interview Aural Rating Scale (MIARS). RESULTS: Patients gave more informational than emotional cues. The most frequent response to emotional cues was distancing followed by acknowledgement. Nurses gave appropriate information in response to the majority of informational cues. Patients' expression of emotional or informational cues did not influence recall; neither did nurses' responses to informational cues. Responses to emotional cues did affect recall. The more nurses responded by giving 'minimal' encouragements (e.g. 'Hmmm'), the more patients recalled, while distancing responses (e.g. switching focus) were associated with lower recall scores. CONCLUSION: Responding to patients' emotions is likely to impact information recall. PRACTICE IMPLICATIONS: These results highlight the importance of addressing patients' expressions of emotions in the context of patient education, as it enhances information recall.

The role of companions in aiding older cancer patients to recall medical information.

OBJECTIVES: This study investigates information recall in unaccompanied and accompanied older cancer patients and their companions. METHODS: One hundred cancer patients (aged > or = 65 years) and 71 companions completed a recall questionnaire after a nursing consultation preceding chemotherapy treatment. Recall was checked against the actual communication in video-recordings of the consultations. Patients also completed measures of anxiety and memory-related beliefs. RESULTS: Findings revealed that recall in patient and companion couples together was higher than their separate recall scores (both proportional and absolute), indicating that they supplement each other. Proportionally, unaccompanied patients recalled almost as much as couples, whereas their absolute recall scores were lower. Younger age and higher education were associated with higher recall in both patients and companions. Patients' memory-related beliefs predicted the recall scores of their companions rather than their own recall score. When patients reported memory complaints, recall was lower in their companion. In contrast, when patients indicated that they did not understand all information, their companion recalled more. CONCLUSIONS: These findings indicate that, although an interrelationship exists between recall in patients and their companions, accompanied patients are likely to benefit from the extra information that their companions remember.

Early response as predictor of final remission in elderly depressed patients.

BACKGROUND: Several studies have attempted to predict the final response or remission based on improvement during the early course of treatment of major depression. There is however a great variation in cut offs used to define early response and in the optimal week to predict final results. OBJECTIVE: To compare different cut offs at different time points early in the treatment of elderly depressed patients. METHOD: A 12 week randomised, controlled trial in 81 elderly inpatients with DSM-IV major depression comparing venlafaxine with nortriptyline. At least 20, 25, 30 or 50% improvement was analysed after 1, 3 and 5 weeks using the Hamilton Depression Rating Scale and the Montgomery Asberg Depression Rating Scale. We plotted sensitivity against 1-specificity and calculated areas under the curve (AUCs). RESULTS: The highest percentage of correctly classified patients is found using at least 50% decrease as cut off in week 5, with acceptable sensitivity (81.8%) and specificity (87.4%). In week 5, the AUCs were 0.891 (95% CI 0.798-0.984) and 0.866 (95% CI 0.789-0.983) for the HAM-D and MADRS, respectively. CONCLUSIONS: Combining the results from our study and the other studies addressing this issue, we suggest that the treatment should be changed in the elderly if after 3-4 weeks less than 30% improvement in depression score has been achieved.

Does age really matter? Recall of information presented to newly referred patients with cancer.

PURPOSE: To examine age- and age-related differences in recall of information provided during oncology consultations. PATIENTS AND METHODS: Two hundred sixty patients with cancer diagnosed with heterogeneous cancers, seeing a medical or radiation oncologist for the first time, participated in the study. Patients completed questionnaires assessing information needs and anxiety. Recall of information provided was measured using a structured telephone interview in which patients were prompted to remember details physicians gave about diagnosis, prognosis, and treatment. Recall was checked against the actual communication in audio-recordings of the consultations. RESULTS: Recall decreased significantly with age, but only when total amount of information presented was taken into account. This indicates that if more information is discussed, older patients have more trouble remembering the information than younger ones. In addition, recall was selectively influenced by prognosis. First, patients with a poorer prognosis recalled less. Next, the more information was provided about prognosis, the less information patients recalled, regardless of their actual prognosis. CONCLUSION: Recall is not simply a function of patient age. Age only predicts recall when controlling for amount of information presented. Both prognosis and information about prognosis are better predictors of recall than age. These results provide important insights into intervention strategies to improve information recall in patients with cancer.

Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized, controlled trial.

BACKGROUND: Up to a third of elderly patients with major depressive disorder do not respond to a first course of treatment with an antidepressant. There is a lack of controlled studies evaluating therapies for treatment-resistant depression in late-life depression, and no randomized controlled studies assessing the efficacy and tolerability of lithium augmentation in elderly patients have been published. METHOD: Twenty-nine elderly inpatients with major depressive disorder according to DSM-IV criteria who had previously failed to respond to 1 or more adequate trials with a tricyclic antidepressant or venlafaxine were included in a 6-week, open, randomized, controlled study with a 2-year follow-up. Subjects received either lithium augmentation or the monoamine oxidase inhibitor phenelzine. The primary outcome criterion was remission, defined as a final score of less than or equal to 10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Response was defined as at least 50% reduction on the MADRS or the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Twenty-eight subjects completed the trial. Remission on the MADRS was achieved by 33.3% of the lithium patients, compared with none of the phenelzine patients (p = .042). Response also showed a difference in favor of lithium augmentation (p = .035 on both the MADRS and the HAM-D). Overall tolerability was good, with no dropouts due to side effects. Subjective memory impairment was more prevalent among patients receiving phenelzine (p = .002), and tremors were significantly more prevalent among patients receiving lithium (p = .002). During the 2-year follow-up, 25 patients (86.2%) did achieve remission, particularly on prolonging the lithium treatment (5 patients) or on lithium augmentation to phenelzine (5 patients). CONCLUSION: Lithium was more effective than phenelzine in elderly patients with treatment-resistant major depressive disorder, while tolerance of both treatments was remarkably good in this group of elderly inpatients with many comorbid medical disorders. CLINICAL TRIALS REGISTRATION: Controlled-trials.com identifier is RCTN93105957.

Venlafaxine versus nortriptyline in the treatment of elderly depressed inpatients: a randomised, double-blind, controlled trial.

BACKGROUND: The majority of the trials in the elderly are outpatient trials which excluded psychotic patients and patients with common comorbid physical disorders. Consequently information is lacking about the more complex cases of elderly depressed patients, as found in inpatient wards. OBJECTIVE: To evaluate the effectiveness of two antidepressants, venlafaxine and nortriptyline, in a clinically representative sample of elderly depressed inpatients. METHOD: A 12-week, double blind, randomised, controlled trial in 81 elderly inpatients from one centre. All patients fulfilled DSM-IV criteria for major depression and were assessed using the Montgomery Asberg Depression Rating Scale, the Hamilton Depression Rating Scale, the Geriatric Depression Scale, the Clinical Global Improvement and the Symptom, sign, and Side-effect Checklist. RESULTS: Overall, remission was achieved by 26 (32.1%) of the patients. There was no statistically significant difference in the number of patients achieving remission on the MADRS between venlafaxine (11 out of 40 patients) and nortriptyline (15 out of 41 patients; p = 0.381) or in any of the secondary outcome variables. The number and severity of side-effects was not statistically different between both treatment groups and most side effects were mild or moderate in intensity. CONCLUSIONS: In elderly inpatients with severe depression, venlafaxine and nortriptyline appeared to be equally effective and equally well tolerated.

Cerebral volume measurements and subcortical white matter lesions and short-term treatment response in late life depression.

BACKGROUND: Late life depression is associated with volumetric reductions of gray matter and increased prevalence of subcortical white matter lesions. Previous studies have shown a poorer treatment outcome in those with more severe structural brain abnormalities. In this study, quantitative and semi-quantitative magnetic resonance imaging (MRI) measures were studied in relation to response to a 12-week controlled antidepressant monotherapy trial. METHODS: MRI (1.5 T) brain scans of 42 elderly inpatients with major depression, of which 23 were non-responder to a controlled 12-week antidepressant monotherapy trial, were acquired. In addition, clinical outcome was assessed after a one year period. Measures were volumes of global cerebral and subcortical structures. RESULTS: After controlling for confounding, no differences were found between non-responders and responders after 12 weeks and after one year in volumes of cerebral gray and white matter, orbitofrontal cortex, hippocampus and white matter lesions. CONCLUSIONS: Structural brain measures associated with late life depression may not be related to short-term treatment response.

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 neuroanatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.

Late-life depression: the differences between early- and late-onset illness in a community-based sample.

BACKGROUND: Several studies have described etiological and clinical differences between elderly depressed patients with early onset of their illness compared to late onset. While most studies have been carried out in clinical samples it is unclear whether the findings can be generalized to the elderly population as a whole. The aim of this study was to compare early-onset (EOD) and late-onset (LOD) depressive illness in a community-based sample. METHODS: Large (n = 3107) representative sample of older persons (55-85 years) in the Netherlands. Two-stage screen procedure to identify elderly with MDD. The Center for Epidemiologic Studies Depression scale (CES-D) was used as a screen and the Diagnostic Interview Schedule (DIS) to diagnose MDD. Data on 90 older persons with early-onset depression and 39 with late-onset depression were available. RESULTS: Those with LOD were older, and more often widowed. Family psychiatric history, vascular pathology, and stressful early and late life events did not differ between groups. EOD subjects had more often double depression and more anxiety. CONCLUSIONS: In a community-based sample we did not detect clear differences in etiology and phenomenology between EOD and LOD. This discrepancy with reports from clinical samples could be due to selection bias in clinical studies. Consequently, all patients with late-life depression deserve a diagnostic work-up of both psychosocial and somatic risk factors and treatment interventions should be focused accordingly.

The role of stigma in the quality of life of older adults with severe mental illness.

BACKGROUND: Stigma and discrimination against older people with mental illness is a seriously neglected problem. OBJECTIVES: (1) To investigate whether stigmatisation of older adults with mental disorder is associated with the type of residential institution they live in or the type of disorder they suffer and (2) to assess the role of stigma experiences in their quality of life. METHODS: A cross-sectional study was carried out of 131 older adults with severe mental illness, recruited in 18 elder care homes operating supported living programmes and in eight psychiatric hospitals throughout the Netherlands. Stigmatisation was assessed with an 11-item questionnaire on stigma experiences associated with mental illness. Quality of life was assessed with the Manchester Short Assessment of Quality of Life (MANSA). To better ascertain the role of stigma, we also assessed in comparison the relationship of social participation to quality of life. RESULTS: Some 57% of the respondents had experienced stigmatisation. No association emerged between residential type or disorder type and the extent of stigma experiences. Stigmatisation did show a negative association with quality of life, a connection stronger than that between social participation and quality of life. CONCLUSION: A feeling of belonging, as contrasted with being excluded, is at least as important for the quality of life of older people with severe mental illness as their actual participation in the community.

The applicability and the inter-rater reliability of the Comprehensive Psychopathological Rating Scale in an elderly clinical population.

BACKGROUND: Psychopathological rating scales are developed and tested on a relatively young population. Their applicability and psychometric performance in the elderly (aged above 60-65 years) are mostly unknown. It is unknown how factors related to ageing or mild cognitive dysfunction influence the applicability and the reliability of these scales. We tested the applicability and the inter-rater reliability of the Dutch version of the Comprehensive Psychopathological Rating Scale (CPRS) on an elderly (age > 60 years) inpatient population. METHODS: The applicability and reliability (expressed by differently weighted Kappa coefficients) of the CPRS was assessed by investigating 62 consecutively referred patients in a ward for elderly patients with acute psychiatric problems that were primarily functional in nature. The results are compared with those found in a younger population. RESULTS: The applicability and reliability of the CPRS on the elderly can be categorised as sufficient to good and is comparable with results for a younger population. We did not find any specific factors influencing the practicality, or the reliability of the CPRS when applied to an elderly group of people with a mild cognitive dysfunction. CONCLUSIONS: The CPRS does not loose its clinical relevance with age, as the applicability and the reliability of the CPRS is not influenced by ageing or mild cognitive dysfunction. The CPRS can detect a broad range of symptoms and due to its psychometric properties it is a useful instrument for measuring an elderly or young population.

Hippocampal changes and white matter lesions in early-onset depression.

BACKGROUND: Hippocampal volume reduction and increased prevalence of subcortical white matter lesions have been reported in late-life depression. We aimed to examine whether total number of subcortical white matter lesions were associated with reduced hippocampal volume in aged female subjects with early-onset depression (< 45 years) and healthy comparison subjects. METHODS: The study included 28 middle-aged and elderly subjects with major depression and 41 age-matched control subjects. Hippocampal, parahippocampal gyrus, and orbitofrontal cortex volumes were determined using manual tracing methods. White matter lesions were rated from T2-weighted MRI scans using a semiquantitative classification scale. RESULTS: After controlling for total brain volume and age, patients had reduced hippocampal volume due to right hippocampal volume decrease (2.84 mL vs. 3.12 mL, F = 16.6, p < .001). Parahippocampal and orbitofrontal volumes did not differ significantly between groups. Multiple linear regression analysis indicated that reduced hippocampal volume did not significantly correlate with total number of subcortical white matter lesions (t = .673, p = .518). CONCLUSIONS: Right hippocampal volume was reduced in aged female early-onset subjects with depression. Total number of subcortical white matter lesions was not associated with the decrease in right hippocampal volume. Our data suggest hippocampal involvement, independent of subcortical white matter lesions, in the neuropathology of early-onset depression.

Effects of recurrent major depressive disorder on behavior and cognitive function in female depressed patients.

Little is known about the effects of recurring depressive episodes on cognition and behavior. The objective of the study was to compare cognitive function and depression-related behavior between healthy female subjects and female outpatients with early-onset DSM-IV recurrent major depressive disorder and to investigate the effect of cumulative depressive duration. Neuropsychological tests and scales for apathy, anhedonia and psychomotor retardation were assessed in 23 female patients and 60 healthy age-matched female controls. Significantly higher levels of apathy, anhedonia and psychomotor retardation, and worse performance on tests of executive function were found in the patient group compared with the healthy controls. In the patient group, cumulative depression duration was not significantly correlated with cognitive function, apathy, anhedonia or psychomotor retardation. The deficits in executive function were not related to the actual level of depression. Mild executive dysfunction may be the effect of the illness process underlying recurrent depressive disorder. Repeated or extensive depressive episodes do not seem to additionally affect cognitive deficits or behavior in depressed patients.

Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

BACKGROUND: Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors. METHOD: The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patient's medical records. RESULTS: Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk. CONCLUSION: Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.

Association of depression duration with reduction of global cerebral gray matter volume in female patients with recurrent major depressive disorder.

OBJECTIVE: The authors investigated the relationship between depression duration and cerebral gray matter volume in female patients with recurrent major depressive disorder. METHOD: Magnetic resonance imaging was used to measure intracranial and total brain volumes as well as gray matter and white matter volumes of the cerebrum; frontal, temporal, parietal, and occipital lobes; cerebellum; and the lateral and third ventricles in 23 female patients with DSM-IV major depression. RESULTS: Correlation and regression analyses showed a significant relationship between total illness duration and cerebral gray matter (including cortical lobe) volume after correction for intracranial volume and age. CONCLUSIONS: Depressive states may lead to changes in global cerebral gray matter volume.

Integrating mental health care into residential homes for the elderly: an analysis of six Dutch programs for older people with severe and persistent mental illness.

Integrating mental health care into residential homes for the elderly is a potentially effective model to address the complex care needs of older chronically mentally ill people. Because no research was available on the implementation of such integrated care in practice, six programs already operating in the Netherlands were analyzed. At the administrative level, three types of cooperative arrangements existed: a psychiatric hospital renting a unit in a residential home for the elderly, a psychiatric hospital stationing mental health professionals in a residential home on a permanent basis, and a residential home employing its own psychiatrically trained staff. At the operational level, contrasting views emerged on the relation-ship between physical and mental health care; these were delivered separately or in integrated form. In either case, the employees trained as elder care workers or as psychiatric nurses had difficulties understanding each other because they held different ideas about good-quality care. These care visions can be characterized as the care-giving approach (care workers) versus the problem-oriented and the rehabilitation approaches (nurses). At the housing level, two models existed: mentally ill patients having apartments in a separate unit (concentrated housing) or located throughout the facility (dispersed housing). The most promising model appears to be the one in which a psychiatric hospital assigns mental health professionals to work in a residential home, where they remain administratively and operationally distinct from the standard residential services. Whether or not the psychiatric residents should be housed in separate units could not be decided based on this study.

Community integration of elderly mentally ill persons in psychiatric hospitals and two types of residences.

OBJECTIVE: Deinstitutionalization policy in the Netherlands has given rise to two new living arrangements for elderly long-term psychiatric patients. Both involve accommodation in mainstream residential homes for elderly persons, either concentrated in a specialized care unit or dispersed throughout the facility. The authors studied the effectiveness of these two housing models for the community integration of such residents compared with accommodation in a psychiatric hospital. METHODS: Three subsamples were selected: 49 residents in six units of concentrated housing, 47 residents in 12 units of dispersed housing, and 78 patients in 24 psychiatric hospital units, for a total sample of 174 participants. These samples were compared in a quasi-experimental, posttest-only design that used four measures of community integration: amount of perceived influence over one's daily life, involvement in social activities, social network size, and frequency of visits received from members of the network. To adjust for differences in the populations, the hospital patients were matched to the residential home residents, and confounding factors were controlled for. RESULTS: Residential homes afforded more privacy, were closer to public services, and had a more diversified population than psychiatric hospitals. Participants in dispersed housing experienced more personal influence over their lives than did hospital patients. Concentrated-housing participants were less enterprising and had smaller social networks. The three groups did not differ in the frequency of visits received from network members. CONCLUSIONS: Community-integrated facilities do not necessarily imply community-integrated residents. Only dispersed-housing residences were an improvement over hospitals, and then solely in terms of residents' influence over their own daily lives. The advantage of the dispersed-housing model is that it resembles independent living while its institutional nature offers structure and protection.