Renerio Fraguas

Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT.

Background and Purpose. Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel‐based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. Methods. rCBF was evaluated with 99m Tc‐single‐photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel‐based analyses of rCBF data were conducted using the statistical parametric mapping software. Results. Significant rCBF reductions in HF patients relative to controls (P < .05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between‐group rCBF differences had been identified. Conclusions. These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and sug est that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.

Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder

Objective: An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the “vascular depression” hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD). Method: We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male ≥45, female ≥55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0–6) by the number of risk factors present. Treatment outcome was measured as response (≥50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17≤7). Results: In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission. Conclusion: Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of “vascular depression” in younger subjects. MDD = major depressive disorder; Ham-D-17 = the 17-item Hamilton Rating Scale for Depression.

Depressão e câncer

A depressao e o transtorno psiquiatrico mais comum em pacientes com câncer, com prevalencias variando de 22% a 29%. Essa variabilidade esta associada a sitios do tumor, estagio clinico, dor, funcionamento fisico limitado, alem da existencia de suporte social. A depressao associa-se a um pior prognostico e aumento da mortalidade pelo câncer. Sindromes depressivas podem ser uma consequencia das terapias antineoplasicas, como ocorre em 21% a 58% dos pacientes recebendo interferon-alfa. Sentimentos de tristeza e desespero podem inibir a procura de cuidado pelos pacientes, dificultando o reconhecimento da depressao. O tratamento com antidepressivos e efetivo e melhora a adesao aos tratamentos do câncer, reduzindo efeitos adversos como nausea, dor e fadiga. Em pacientes com câncer, tratamento previo com antidepressivos pode minimizar sintomas depressivos induzidos por interferon-alfa. O tratamento com antidepressivos parece ser uma estrategia efetiva para prevenir o desenvolvimento da depressao induzida por interferon-alfa. Intervencoes psicossociais, como tecnicas de relaxamento, terapia individual e em grupo, tambem podem ser utilizadas na reducao dos sintomas depressivos e de estresse em pacientes com câncer.

Stroke lesion in cortical neural circuits and post-stroke incidence of major depressive episode: a 4-month prospective study.

Abstract Objective. Little is known about the relevance of lesion in neural circuits reported to be associated with major depressive disorder. We investigated the association between lesion stroke size in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuit and incidence of major depressive episode (MDE). Methods. We enrolled 68 patients with first-ever ischemic stroke and no history of major depressive disorder. Neurological and psychiatric examinations were performed at three time-points. We diagnosed major depressive episode, following DSM-IV criteria. Lesion location and volume were determined with magnetic resonance imaging, using a semi-automated method based on the Brodmann Cytoarchitectonic Atlas. Results. Twenty-one patients (31%) experienced major depressive episode. Larger lesions in the left cortical regions of the LCSPT circuit (3,760 vs. 660 mm3; P = 0.004) were associated with higher incidence of MDE. Secondary analyses revealed that major depressive episode was associated with larger lesions in areas of the medial prefrontal cortex including the ventral (BA24) and dorsal anterior cingulate cortex (BA32) and subgenual cortex (BA25); and also the subiculum (BA28/36) and amygdala (BA34). Conclusions Our findings indicate that depression due to stroke is aetiologically related to the disruption of the left LCSPT circuit and support the relevance of the medial prefrontal cortex dysfunction in the pathophysiology of depression.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Association between depression and development of coronary artery disease: pathophysiologic and diagnostic implications.

Depression and coronary artery disease (CAD) are both extremely prevalent diseases. In addition, compromised quality of life and life expectancy are characteristics of both situations. There are several conditions that aggravate depression and facilitate the development of CAD, as well as provoke a worse prognosis in patients with already established CAD: inferior adherence to medical orientations (medications and life style modifications), greater platelet activation and aggregation, endothelial dysfunction, and impaired autonomic dysfunction (lowered heart rate variability). Recent literature has shown that depression alone is becoming an independent risk factor for cardiac events both in primary and secondary prevention. As the diagnosis of depression in patients with heart disease is difficult, due to similarities of symptoms, the health professional should perform a careful evaluation to differentiate the clinical signs of depression from those related with general heart diseases. After a myocardial infarction, depression is an independent risk factor for mortality. Successful therapy of depression has been shown to improve patients’ quality of life and cardiovascular outcome. However, multicentric clinical trials are needed to support this inference. A practical liaison between qualified professionals is necessary for the better management of depressed patients with excess risk in developing CAD. Accordingly, pathophysiological and clinical implications between depression and CAD are discussed in this article.

Pharmacological and Combined Interventions for the Acute Depressive Episode: Focus on Efficacy and Tolerability

Background: Use of antidepressants is the gold standard therapy for major depression. However, despite the large number of commercially available antidepressant drugs there are several differences among them in efficacy, tolerability, and cost-effectiveness. In addition the optimal augmentation strategy is still not clear when dealing with treatment-resistant depression, a condition that affects 15% to 40% of depressed patients. Methods: We therefore reviewed the main characteristics of these drugs regarding their efficacy, tolerability, side effects and cost-effectiveness, by accessing all meta-analyses and systematic reviews published from 2004 to 2009. In addition, we reviewed the augmentation strategy of associated antidepressants with neurostimulation therapies (such as transcranial magnetic stimulation [TMS] and transcranial direct current stimulation [tDCS]). A search was undertaken in MEDLINE, Web of Science, Cochrane, and Scielo databases. We included: 21 meta-analyses of antidepressant trials, 15 neurostimulation clinical trials and 8 studies of pharmacoeconomics. We then performed a comprehensive review on these articles. Results and Conclusion: Although recent meta-analyses suggest sertraline and escitalopram might have increased efficacy/tolerability, other studies and large pragmatic trials have not found these to be superior to other antidepressant drugs. Also, we did not identify any superior drug in terms of cost-effectiveness due to the different designs observed among pharmacoecomics studies. Side effects such as sexual dysfunction, gastrointestinal problems and weight gain were common causes of discontinuation. Tolerability was an important issue for novel neurostimulation interventions, such as TMS and tDCS. These therapies might be interesting augmentation strategies, considering their benign profile of side effects, if proper safety parameters are adopted.

Autonomic reactivity to induced emotion as potential predictor of response to antidepressant treatment.

Distinct factors have been identified as potential predictors of antidepressant treatment response. Although autonomic function changes have been described in depressive subjects, their value as predictors of antidepressant response has not been systematically evaluated. Eight un-medicated patients with major depressive order (MDD) have their skin conductance (SC) and heart rate variability (HRV) measured at basal condition and during four induced emotional states: happy, angry, sad and neutral. The high frequency (HF) and low frequency (LF) power parameters of HRV were assessed. Subsequently, patients were treated with fluoxetine 20 mg/day for 8 weeks. The antidepressant response was measured with the Beck Depression Inventory (BDI). The BDI percentage reduction correlated significantly with HRV responses during sad condition in LF power, and during happy condition with LF/HF ratio. The BDI percentage reduction also correlated significantly with HR responses in happy and in neutral conditions, and also with SC responses in neutral condition. These preliminary findings indicate that automatic responses to induced emotions may predict antidepressant response in MDD patients. Confirmatory studies are warranted.

Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression

BACKGROUND We compared transcranial direct‐current stimulation (tDCS) with a selective serotonin‐reuptake inhibitor for the treatment of depression. METHODS In a single‐center, double‐blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30‐minute, 2‐mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17‐item Hamilton Depression Rating Scale (HDRS‐17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention‐to‐treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, ‐2.3 points; 95% confidence interval [CI], ‐4.3 to ‐0.4; P=0.69) was lower than the noninferiority margin of ‐2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new‐onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS In a single‐center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10‐week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT‐TDCS ClinicalTrials.gov number, NCT01894815.)

A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms

BACKGROUND Little is known about the treatment of depression in older patients with heart failure. This study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. METHODS We enrolled 72 older outpatients with ejection fraction <50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. RESULTS A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05+9.74 vs 9.44+9.25, P=.082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. CONCLUSION Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure.