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

Pharmacological and combined interventions for the acute depressive episode: focus on efficacy and tolerability

Andre R Brunoni1, Renerio Fraguas Jr1, Felipe Fregni21Department and Institute of Psychiatry, University of Sao Paulo, Brazil; 2Laboratory of Neuromodulation, Spaulding Rehabilitation Center, Harvard Medical School and Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USABackground: 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.Keywords: acute depressive episode, pharmacological interventions, combined intervention

Psychosocial and health-related stressors faced by undergraduate medical students

Stress is common among medical students and is associated with increased risk of burnout, anxiety and depression, alcohol and drug abuse, social difficulties, suicidal ideation and suicide. The purpose of this literature review was to identify the sources of stress in undergraduate medical students. In order to achieve that, we conducted a search for papers published in the Medline database from 2003 to 2014. Due to the extension of sources of stress identified in this population and our interest on the subject, we chose to include only papers that addressed specifically two main categories of stressors: psychosocial and/or health-related. We divided the psychosocial sources into four groups: social, familial, infrastructural and not specified. Among the most relevant social sources, we found loneliness, social isolation, interpersonal conflict, social relationships and worry about the future. Familial sources of stress included high parental expectation, family problems and financial problems. Among the infrastructural sources, we found relevance for absence of an optimal place to study outside the university and accommodation away from home, particularly for first-year students and for males. Few studies have focused on health-related sources of stress. The most relevant sources of health-related stress were the quality of food in mess and sleeping difficulties. While the relevance of some sources varied according to the medical school, the importance of some sources such as quality of food in mess, sleeping difficulties and worry about the future was consensual among the studies. Of relevance is the fact that most of these sources of stress can be reversed. For example, a healthy relationship has been reported to protect against stress; thus, programmes aimed at the improvement of students’ relationships may be effective in decreasing the stress associated with loneliness, social isolation and interpersonal conflict. The relevance of a stressor should be evaluated in each school taking into consideration the influence of its context peculiarities. Although several studies have reported the sources of stress, studies looking specifically at each source, investigating its impact, related factors and feasibility of change are warranted.O estresse é comum entre os estudantes de medicina e tem sido associado com aumento do risco de burnout, ansiedade e depressão, abuso de álcool e drogas, dificuldades sociais, ideação suicida e suicídio. O objetivo desta revisão de literatura foi identificar as causas de estresse em estudantes de medicina. Para isso, realizamos uma busca por artigos publicados na base de dados Medline, de 2003 a 2014. Devido à extensão das fontes de estresse identificados nesta população e nosso interesse sobre o assunto, optamos por incluir apenas trabalhos que abordaram especificamente duas principais categorias de estressores: os psicossociais e os relacionados com a saúde. Dividimos as fontes psicossociais em quatro grupos: sociais, familiares, de infra-estrutura e não especificados. Dentre as causas sociais mais relevantes, encontramos solidão, isolamento social, conflitos interpessoais, relações sociais e preocupação com o futuro. As causas familiares de estresse incluíram alta expectativa dos pais, problemas familiares e problemas financeiros. Entre as causas de infra-estrutura, encontramos relevância para a ausência de um lugar ideal para estudar fora da universidade e alojamento longe de casa, especialmente para alunos do primeiro ano e para o sexo masculino. Poucos estudos têm focado nas causas de estresses relacionados com a saúde. As causas mais relevantes relacionadas à saúde foram qualidade ruim dos alimentos e dificuldades com o sono. Enquanto a relevância de algumas causas de estresse variou de acordo com a faculdade, a importância de algumas causas foi consensual entre os estudos, tais como: qualidade ruim de alimentos, dificuldades com o sono e preocupação com o futuro. Destacamos como relevante o fato de que a maioria das causas de estresses encontradas podem ser revertidas. Por exemplo, uma relação saudável tem sido relatada como proteção contra o stress; portanto, programas que visam a melhoria das relações entre os alunos podem ser eficazes em diminuir o estresse associado à solidão, isolamento social e conflitos interpessoais. A relevância de um estressor deve ser avaliada em cada faculdade, levando em consideração a influência das peculiaridades do seu contexto. Embora vários estudos tenham relatado as causas de estresse, são necessários estudos que enfoquem especificamente cada causa, investigando seu impacto, fatores relacionados e, a viabilidade de mudança

Development of the Ketamine Side Effect Tool (KSET)

Background: Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments. Methods: Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts. Results: The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation. Limitations: Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites. Conclusions: The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries

The Influence of Depression on the Psychometric Properties of the Maslach Burnout Inventory–Human Services Survey: A Cross-Sectional Study With Nursing Assistants

Background: The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) is the most commonly used instrument to assess burnout. Although various factors have been reported to influence its validity, the influence of major depressive disorder (MDD) has not been previously considered. We developed this study to investigate the influence of MDD on the psychometric properties of the MBI-HSS in nursing assistants.Results: From a sample of 521 nursing assistants, we found in those with MDD (n = 138, 24.56%) a degree of data misfit into the model, revealed by non-acceptable values for the root mean square error of approximation (RMSEA; 0.073; p = 0.004) and for the comparative fit index (CFI; 0.912), while in the non-MDD group these indices were acceptable and good, respectively, for RMSEA (0.048; p = 0.639) and for CFI (0.951). Also, we found higher coefficients of correlation among MBI-HSS factors and less items loading properly in their respective factors in the MDD subset, when compared to the non-MDD subset. For the total sample, while original 3-factor solution was an acceptable model, the bifactor model fitted data better.Conclusions: MDD may impair the construct validity of MBI-HSS subscales, by increasing measurement error and decreasing model fitness. Therefore, researchers and health professionals should be aware of potential changes in the psychometric properties of the MBI-HSS when applied in subjects with depression

Loss of interest, depressed mood and impact on the quality of life: Cross-sectional survey

Abstract\ud \ud \ud \ud Background\ud \ud Depressive symptoms and chronic disease have adverse effects on patients' health-related quality of life (H-RQOL). However, little is known about this effect on H-RQOL when only the two core depressive symptoms - loss of interest and depressed mood - are considered. The objective of this study is to investigate H-RQOL in the presence of loss of interest and depressed mood at a general medical outpatient unit.\ud \ud \ud \ud Methods\ud \ud We evaluated 553 patients at their first attendance at a general medical outpatient unit of a teaching hospital. H-RQOL was assessed with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Depressed mood and loss of interest were assessed by the Primary Care Evaluation of Mental Disorders (PRIME-MD)-Patient Questionnaire. A physician performed the diagnosis of chronic diseases by clinical judgment and classified them in 13 possible pre-defined categories. We used multiple linear regression to investigate associations between each domain of H-RQOL and our two core depression symptoms. The presence of chronic diseases and demographic variables were included in the models as covariates.\ud \ud \ud \ud Results\ud \ud Among the 553 patients, 70.5% were women with a mean age of 41.0 years (range 18-85, SD ± 15.4). Loss of interest was reported by 54.6%, and depressed mood by 59.7% of the patients. At least one chronic disease was diagnosed in 59.5% of patients; cardiovascular disease was the most prevalent, affecting 20.6% of our patients. Loss of interest and depressed mood was significantly associated with decreased scores in all domains of H-RQOL after adjustment for possible confounders. The presence of any chronic disease was associated with a decrease in the domain of vitality. The analysis of each individual chronic disease category revealed that no category was associated with a decrease in more than one domain of H-RQOL.\ud \ud \ud \ud Conclusion\ud \ud Loss of interest and depressed mood were associated with significant decreases in H-RQOL. We recommend these simple tests for screening in general practice.We gratefully acknowledge all practice staff for their co-operation and support in this study, and all the patients who took part. This project was supported by The State of São Paulo Research Foundation (FAPESP), Brazil (00669-9)