Validation of a treatment algorithm for major depression in an older Brazilian sample.

OBJECTIVE: The aim of this study was to investigate the effectiveness of a modified version of the Duke Somatic Algorithm Treatment for Geriatric Depression (STAGED) in a Brazilian sample of older patients with major depression. Besides, we aimed to investigate possible baseline predictive factors for remission in this sample. METHODS: Sixty-seven depressed individuals were treated according to STAGED over 24 weeks in a prospective cohort design with follow-up. All patients had criteria for major depression and were at least 60 years of age at baseline enrollment. RESULTS: During this follow-up, 56 patients could be classified in remitted or not remitted group, 42.85% reached remission, and 57.14% did not reach remission. These results are even better than those found in the original study, probably due to the lower baseline depression severity of our sample. When baseline characteristics were compared between remitted and not remitted groups, scores of Mini Mental State Examination and Cambridge Cognitive Examination (CAMCOG) were the only variables with statistical significant difference (p < 0.05) between groups. Logistic regression analysis was carried out to try to predict remission and statistical significance (p < 0.05) was found only for baseline MMSE scores. It may mean that patients with mixed cognitive disorders and mood disorders have a worse course of depression. CONCLUSIONS: This version of STAGED seems to be a useful strategy for treatment of depression in late life. Baseline general cognitive performance might be useful to predict remission of depression in older patients with mild to moderate depression. Further research with different population characteristics should be conducted in order to evaluate its usefulness and feasibility in different settings.

Treatment of depression in older adults.

Depression is the most frequent mental disorder in older people, often causing emotional distress and reduced quality of life. Despite its clinical significance, depression remains underdiagnosed and inadequately treated in older patients. Regarding prognosis, data suggest that almost 70% of patients, treated long enough and with appropriate doses, recover from an index episode of depression. Antidepressants are efficient for treating depressed outpatients with several comorbid physical diseases as well as hospitalized patients, with selective serotonin reuptake inhibitors being the antidepressants of choice for older patients. Available data can guide pharmacological treatment in both the acute and maintenance stages, but further research is required to guide clinical strategies when remission is not achieved. Approaches for the management of resistance to treatment are summarized, including optimization strategies, drug changes, algorithms, and combined and augmentation pharmacological treatments. Finally, additional therapeutic choices such as electroconvulsive therapy, transcranial magnetic stimulation, and integrated psychotherapy are presented.

Structural brain changes as biomarkers and outcome predictors in patients with late-life depression: a cross-sectional and prospective study.

The relationship between structural changes in grey matter and treatment response in patients with late-life depression remains an intriguing area of research. This magnetic resonance imaging (MRI) study compares the baseline grey matter volume of elderly people with and without major depression (according to the DSM-IV-TR criteria) and assesses its association with antidepressant treatment response. Brain MRI scans were processed using statistical parametric mapping and voxel-based morphometry. The sample consisted of 30 patients with depression and 22 healthy controls. We found a significant volumetric reduction in the orbitofrontal cortex bilaterally in patients in comparison with controls. According to their remission status after antidepressant treatment, patients were classified as remitted or not remitted. Compared with controls, remitted patients showed a volumetric reduction in the orbitofrontal cortex bilaterally and in another cluster in the right middle temporal pole. Non-remitted patients showed an even greater volumetric reduction in the orbitofrontal cortex bilaterally compared with controls. To investigate predictive factors of remission after antidepressant treatment, we used a logistic regression. Both baseline Mini Mental State Examination score and baseline left superior lateral orbitofrontal cortex volume (standardized to the total grey matter volume) were associated with remission status. Our findings support the use of regional brain atrophy as a potential biomarker for depression. In addition, baseline cognitive impairment and regional grey matter abnormalities predict antidepressant response in patients with late-life depression.

DTI voxelwise analysis did not differentiate older depressed patients from older subjects without depression.

INTRODUCTION: Neuroimaging has been widely used in studies to investigate depression in the elderly because it is a noninvasive technique, and it allows the detection of structural and functional brain alterations. Fractional anisotropy (FA) and mean diffusivity (MD) are neuroimaging indexes of the microstructural integrity of white matter, which are measured using diffusion tensor imaging (DTI). The aim of this study was to investigate differences in FA or MD in the entire brain without a previously determined region of interest (ROI) between depressed and non-depressed elderly patients. METHOD: Brain magnetic resonance imaging scans were obtained from 47 depressed elderly patients, diagnosed according to DSM-IV criteria, and 36 healthy elderly patients as controls. Voxelwise statistical analysis of FA data was performed using tract-based spatial statistics (TBSS). RESULTS: After controlling for age, no significant differences among FA and MD parameters were observed in the depressed elderly patients. No significant correlations were found between cognitive performance and FA or MD parameters. CONCLUSION: There were no significant differences among FA or MD values between mildly or moderately depressed and non-depressed elderly patients when the brain was analyzed without a previously determined ROI.

Cholinesterase inhibitors as adjunctive therapy in patients with schizophrenia and schizoaffective disorder: a review and meta-analysis of the literature.

BACKGROUND: Cognitive deficits have been described in patients with schizophrenia from the first descriptions of dementia praecox to current concepts of cognitive dysmetria. Nevertheless, little is known about how to deal with them. In Alzheimer disease, cholinergic deficit is found and cholinesterase inhibitors have been used to delay the progression of memory and cognitive dysfunction. Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia. OBJECTIVE: To evaluate cognitive and clinical effects of adjunctive cholinesterase inhibitors in patients with schizophrenia and schizoaffective disorder. METHOD: We conducted a literature search on PubMed and EMBASE (up to December 2008) for articles that investigated adjunctive cholinesterase inhibitors in patients with schizophrenia. The terms 'schizophrenia', 'acetylcholinesterase inhibitors', 'rivastigmine', 'donepezil', 'galantamine' and 'cognitive deficit' were searched with restriction for English language and without a year limit. All articles that presented original data from randomized, double-blind, placebo-controlled trials with donepezil, rivastigmine or galantamine in patients with schizophrenia or schizoaffective disorder were included in the meta-analysis. Studies were excluded for the following reasons: (i) case study/letter/correspondence/review; (ii) animal study; (iii) molecular/genetic investigation; and (iv) inclusion of patients with schizophrenia and co-morbid dementia. Few appropriate data for meta-analysis were found because of the large heterogeneity of the assessment instruments used. Nevertheless, effects of cholinesterase inhibitors in some cognitive domains (executive function, memory and language), psychopathology (using the Positive and Negative Syndrome Scale) and extrapyramidal symptoms could be analysed. RESULTS: Six open-label and 24 double-blind studies were found. In five open-label studies there was an improvement in memory, attention and executive functions. Thirteen double-blind studies (four with rivastigmine, six with donepezil and three with galantamine) contributed to the meta-analysis. Significant improvement was found in this analysis for memory and the Trail Making test part A. CONCLUSIONS: The reviewed studies suggest that specific cognitive deficits (memory, and the motor speed and attention part of executive function) of patients with schizophrenia and schizoaffective disorder are responsive to rivastigmine, donepezil and galantamine as adjunctive therapy. Confirmatory studies are needed to determine the clinical utility of this treatment strategy.