Avaliação da incidência de uso de antidepressivos em estudantes de medicina do estado de Alagoas / Evaluation of the incidence of antidepressant use among medical students in the state of Alagoas

O presente estudo objetivou determinar a frequência do uso de antidepressivos entre os estudantes de Medicina do Estado de Alagoas, dessa forma, consiste em um estudo prospectivo e transversal, realizado nas instituições de ensino superior do Estado de Alagoas possuidoras da graduação de Medicina. Critérios de inclusão foram estar matriculado e frequentando o curso, cursando do primeiro ao quarto ano e possuir 18 anos ou mais. Já os critérios de exclusão foram ser do quinto ou sexto ano de graduação; possuir idade menor que 18 anos, mesmo que emancipado. Através de questionário autopreenchido (informações sociodemográficas, estilo de vida e inventário de Ansiedade de Beck), foram entrevistados 342 acadêmicos de forma aleatória. Os dados adquiridos foram digitados, tabulados e analisados. Este estudo teve aprovação do Comitê de Ética em Pesquisa. Todos os participantes leram e assinaram o Termo de Consentimento Livre e Esclarecido em conformidade aos critérios da resolução 466/12. Dos entrevistados, 15% recorrem a antidepressivo e 85% não fazem uso desse tipo de fármaco. Mesmo dando uma percentagem baixa, ainda é preocupante e bastante importante abordar sempre esse tema e reformular o ensino médico, de modo a diminuir os níveis de estresse e ansiedade dos estudantes (AU).

This study aimed to determine the frequency of antidepressant use among medical students in the State of Alagoas, thus consisting of a prospective and cross-sectional study carried out in higher education institutions in the State of Alagoas that offer undergraduate medical education. Inclusion criteria were being enrolled and attending the course, from the first to the fourth year, and being 18 years old or older. The exclusion criteria were being in the fifth or sixth year of medical school; being younger than 18 years old, even if emancipated. Through a self-completed questionnaire (sociodemographic information, lifestyle, and Beck's Anxiety Inventory), 342 students were randomly interviewed. The data were typed, tabulated and analyzed. This study was approved by the Research Ethics Committee. All participants who participated read and signed the Informed Consent Form according to the criteria of resolution 466/12. Fifteen percent of the respondents use antidepressants and 85% do not use this type of drug. Even giving a low percentage, it is still worrisome and quite important to always address this issue and reformulate medical education in order to decrease the levels of stress and anxiety among students (AU).

Eficácia e segurança de Aripiprazol comparado a medicamentos disponíveis no SUS para o tratamento de transtorno de déficit de atenção com hiperatividade em crianças e adolescentes / Effectiveness and safety of aripiprazole compared to other medicines available in Brazilian Public Health for treatment of attention deficit disorder with hyperactivity: rapid review

Tecnologia: Aripiprazol. Indicação: Tratamento de transtorno de déficit de atenção com hiperatividade em crianças e adolescentes. Pergunta: O aripiprazol é mais eficaz e tolerável que os medicamentos disponíveis no SUS (bupropiona e antidepressivos (amitriptilina, nortriptilina, fluoxetina, clomipramina, risperidona) para o tratamento de transtorno de déficit de atenção e hiperatividade em crianças e adolescentes? Métodos: Revisão rápida de evidências de ensaios clínicos randomizados com levantamento bibliográfico realizado na base de dados PUBMED, EMBASE, Cochrane Library, PsycInfo, utilizando estratégia estruturada de busca. A qualidade metodológica dos ECR foi avaliada com a escala PEDro (Physiotherapy Evidence Database). Resultados: Foram selecionados dois estudos clínicos randomizados, que atendiam aos critérios de inclusão. Conclusão: As evidências demonstraram tanto o aripiprazol quanto a risperidona apresentam redução dos sintomas emocionais de déficit de atenção e hiperatividade mediante avaliação das escalas e ambas apresentaram taxa de abandono de tratamento devido a efeitos adversos e não se mostraram uma opção econômica

Technology: Aripiprazole. Indication: Treatment of attention deficit hyperactivity disorder in children and adolescents. Question: Is aripiprazole more effective and tolerable than drugs available in the SUS (bupropion and antidepressants (amitriptyline, nortriptyline, fluoxetine, clomipramine, risperidone) for the treatment of attention deficit hyperactivity disorder in children and adolescents? Methods: Rapid review of evidence of randomized clinical trials with a bibliographic search done in PUBMED, EMBASE, Cochrane Library and PsycInfo databases using a structured search strategy. The methodological quality of the randomized clinical trials was evaluated with the PEDro scale (Physiotherapy Evidence Database). Results: Two randomized clinical studies were selected, which met the inclusion criteria. Conclusion: The evidence showed that both aripiprazole and risperidone present a reduction in the emotional symptoms of attention deficit and yperactivity according to the scales and both presented a rate of abandonment of treatment due to and adverse effects and did not prove to be an economical option

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plants acting on the central nervous system: review plantas com ação no sistema nervoso central que constam na relação nacional de plantas medicinais de interesse ao sus (RENISUS) / Plantas con acción sobre el sistema nervioso central incluidas en la lista nacional de plantas medicinales de interés para sus (RENISUS)

A depressão é uma doença grave que atinge a população em geral, estudos epidemiológicos estimam que a prevalência da depressão ao longo da vida no Brasil está em torno de 15,5%. Os fatores que desencadeiam o aparecimento da depressão incluem fatores sociais, psicológicos, biológicos e também fatores externos específicos como eventos estressantes, solidão, consumo de álcool e drogas, doenças crônicas e dar á luz (depressão pós-parto). O objetivo da presente pesquisa consistiu em realizar uma revisão bibliográfica sobre as principais plantas medicinais com ação antidepressiva. A ansiedade vem se tornando um dos principais problemas da atualidade, sendo intensificada pela pandemia causada pelo coronavírus, onde constatou-se que durante o pico da pandemia onde os casos confirmados de COVID-19 no Brasil ascenderam de 45.757 para 330.890, e as mortes, de 2.906 para 21.048, o sentimento de tristeza/depressão atingiu 40% dos adultos brasileiros. Os sintomas de depressão podem ser amenizados quando a disponibilidade sináptica de monoaminas são aumentadas, e esse aumento pode ocorrer através da diminuição da metabolização desses neurotransmissores. Neste sentido, busca-se através da farmacoterapia a utilização de antidepressivos que disponibilizem as monoaminas na fenda sináptica. A escolha do fármaco é feita com base nos sintomas da depressão e na boa resposta a uma determinada classe de antidepressivos. Em fevereiro de 2009 o Ministério da saúde lançou a Relação Nacional de Plantas Medicinais de Interesse ao SUS (RENISUS), contendo 71 espécies vegetais que são distribuídas de forma in natura nas unidades básicas de saúde (UBS). Destas, somente três espécies apresentam efeito antidepressivo e ansiolítico comprovados na literatura sendo Matricharia chamomilla, Erytrinum mulungu e a Passiflora incarnata que também fazem parte da RENISUS. Além destas, outras espécies como a Melissa officinalis, Lippia alba, Valeriana officinalis e Piper methysticum são utilizadas pela população para tratar ansiedade, insônia e depressão, sugerindo desta forma que estas espécies sejam incluídas na RENISUS.

Depression is a serious disease that affects the general population, epidemiological studies estimate that the prevalence of depression throughout life in Brazil is around 15.5%. The factors that trigger the onset of depression include social, psychological, biological and also specific external factors such as stressful events, loneliness, alcohol and drug consumption, chronic diseases and giving birth (postpartum depression). The objective of the present research was to carry out a literature review on the main medicinal plants with antidepressant action. Anxiety has become one of the main problems of today, being intensified by the pandemic caused by the coronavirus, where it was found that during the peak of the pandemic where confirmed cases of COVID-19 in Brazil rose from 45,757 to 330,890, and deaths, from 2,906 to 21,048, the feeling of sadness/depression reached 40% of Brazilian adults. Symptoms of depression can be alleviated when synaptic availability of monoamines is increased, and this increase can occur through decreased metabolization of these neurotransmitters. In this sense, the use of antidepressants that make monoamines available in the synaptic cleft is sought through pharmacotherapy. The choice of drug is based on symptoms of depression and good response to a particular class of antidepressants. In February 2009, the Ministry of Health launched the National List of Medicinal Plants of Interest to the SUS (RENISUS), containing 71 plant species that are distributed in natura form in basic health units (UBS). Of these, only three species have antidepressant and anxiolytic effects proven in the literature, being Matricharia chamomilla, Erytrinum mulungu and Passiflora incarnata, which are also part of RENISUS. In addition to these, other species such as Melissa officinalis, Lippia alba, Valeriana officinalis and Piper methysticum are used by the population to treat anxiety, insomnia and depression, thus suggesting that these species are included in RENISUS.

Los estudios epidemiológicos estiman que la prevalencia de la depresión a lo largo de la vida en Brasil es de alrededor del 15,5%. Los factores que desencadenan la aparición de la depresión son sociales, psicológicos, biológicos y también factores externos específicos, como los acontecimientos estresantes, la soledad, el consumo de alcohol y drogas, las enfermedades crónicas y el parto (depresión posparto). El objetivo de esta investigación fue realizar una revisión bibliográfica sobre las principales plantas medicinales con acción antidepresiva. La ansiedad se ha convertido en uno de los principales problemas de la actualidad, intensificándose por la pandemia causada por el coronavirus, donde se encontró que durante el pico de la pandemia donde los casos confirmados de COVID-19 en Brasil aumentaron de 45.757 a 330.890, y las muertes, de 2.906 a 21.048, el sentimiento de tristeza/depresión alcanzó el 40% de los adultos brasileños. Los síntomas de la depresión pueden aliviarse cuando se aumenta la disponibilidad sináptica de las monoaminas, y este aumento puede producirse mediante una disminución de la metabolización de estos neurotransmisores. En este sentido, se busca a través de la farmacoterapia el uso de antidepresivos que hagan disponibles las monoaminas en la hendidura sináptica. La elección del fármaco se hace en función de los síntomas de la depresión y de la buena respuesta a una clase concreta de antidepresivos. En febrero de 2009, el Ministerio de Salud lanzó la Lista Nacional de Plantas Medicinales de Interés para el SUS (RENISUS), que contiene 71 especies de plantas que se distribuyen in natura en unidades básicas de salud (UBS). De ellas, sólo tres especies tienen efectos antidepresivos y ansiolíticos probados en la literatura: Matricharia chamomilla, Erytrinum mulungu y Passiflora incarnata, que también forman parte del RENISUS. Además de éstas, otras especies como Melissa officinalis, Lippia alba, Valeriana officinalis y Piper methysticum son utilizadas por la población para tratar la ansiedad, el insomnio y la depresión, lo que sugiere que estas especies se incluyan en el RENISUS.

Combinación de antidepresivos vs. aumentación con antipsicóticos atípicos tras no lograr la remisión en la depresión unipolar / Combination of antidepressants vs. augmentation with atypical antipsychotics upon failure to achieve remission in unipolar depression

RESUMEN: Introducción: Lograr la recuperación funcional lo más rápido posible en el tratamiento de la depresión unipolar es un reto que la práctica clínica debe tratar de afrontar en la actualidad, ya que cualquier retraso en lograr la remisión de los síntomas es predictivo de un mayor número de recurrencias y mayores tasas de morbimortalidad. En esta revisión comprensiva, nuestro objetivo es guiar a los clínicos en su elección de aumentar con antipsicóticos atípicos o combinar el fármaco de referencia con un segundo antidepresivo, después de que se haya optimizado la dosis del antidepresivo seleccionado inicialmente y/o se haya cambiado el antidepresivo, sin lograr remisión, o bien cuando solo han obtenido una respuesta parcial después de un tiempo suficiente a una dosis apropiada. Estas decisiones surgen con frecuencia en la práctica clínica diaria. Metodología: Se realizó una búsqueda sistemática en PubMed bajo varias combinaciones clave de palabras, resultando en 230 informes. Después de aplicar los criterios de inclusión y según el título y el resumen, el número final de informes seleccionados para la revisión completa fue de 113. Se respondieron dos preguntas principales con base en estos estudios: 1) ¿Existe evidencia para recomendar claramente la combinación de antidepresivos versus potenciación con antipsicóticos (y el momento correcto para hacerlo) en la depresión unipolar no respondedora, una vez que las estrategias de optimización o de cambio han fallado en obtener la remisión? y 2) ¿Es posible identificar algunas características clínicas para guiar la decisión de combinación de antidepresivos versus potenciación con agentes antipsicóticos? Resultados: Según nuestro análisis, no hay datos disponibles para seleccionar una estrategia de otra de manera clara. Sin embargo, sugerimos favorecer una combinación o estrategia de aumento, basada en un enfoque de "tratamiento contra objetivos dianas" para perfilar al paciente, considerando una o dos características clínicas predominantes que permanecen activas como parte de una depresión mayor con respuesta parcial. Un adecuado análisis de los dominios sintomáticos presentes, una visión crítica de las guías clínicas actuales y de las opciones preferidas, considerar la bipolaridad oculta como uno de los principales diagnósticos diferenciales y adoptar una actitud enérgica pero lúcida en esta etapa del tratamiento son, a nuestro juicio, fundamentales para lograr recuperación ad integrum del paciente.

ABSTRACT Introduction: achieving functional recovery as quickly as possible in the treatment of unipolar depression is a challenge that clinical practice must try to meet nowadays, since any delay in accomplishing remission of the symptoms is predictive of a larger number of recurrences and higher morbidity and mortality rates. In this topical review we aim to guide clinicians in their choice to augment with atypical antipsychotics or to combine the baseline drug with a second antidepressant, after the dose of the antidepressant initially selected has been optimized and/or the antidepressant has been changed, not achieving remission, or resulting only in a partial response after sufficient time at an appropriate dose. These decisions arise frequently in everyday clinical practice. Methodology: a systematic search in PubMed was performed under several key combinations of words, resulting in 230 reports. After applying inclusion criteria and based in title and abstract, the final number of reports selected for full revision were 113. Two main questions were answered based on these studies: 1) Is there evidence to clearly recommend combination of antidepressants vs. augmentation with antipsychotics (and the correct moment to do it) in non-responsive unipolar depression, once optimization or switching strategies have failed to obtain remission? and 2) Is it possible to identify some clinical features to guide the decision of combination of antidepressants vs. augmentation with antipsychotic agents? Results: According to our analysis, there is no data available to select one strategy from another in a clear-cut manner. Nevertheless, we suggest favoring a combination or augmentation strategy, based in a "treating to target" approach to profile the patient, considering one or two predominant clinical features that remain active as part of a major depression with partial response. Proper analysis of the symptomatic domains present, a critical view of current clinical guidelines and preferred options, considering hidden bipolarity as one of the main differential diagnoses and adopting an energetic but lucid attitude at this stage of treatment are, in our view, fundamental for achieving ad integrum patient recovery.

High efficiency of left superior frontal gyrus and the symptom features of major depressive disorder / 中南大学学报(医学版)

OBJECTIVES@#Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment.@*METHODS@#Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki).@*RESULTS@#Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment.@*CONCLUSIONS@#There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.@*METHODS@#Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.@*RESULTS@#The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01).@*CONCLUSION@#The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Lisdexanfetamina comparada a Metilfenidato ou antidepressivos no tratamento de TDAH em crianças e adolescentes: revisão rápida de evidências / Lisdexamfetamine compared to Methylphenidate or antidepressants for treatment of ADHD: rapid response review of evidence

Lisdexanfetamina e drogas disponíveis no SUS (metilfenidato, bupropiona, amitriptilina, clomipramina, nortriptilina). Indicação: Transtorno do Déficit de Atenção e Hiperatividade (TDAH) em crianças e adolescentes. Pergunta: Lisdexanfetamina é eficaz e segura para melhoria de sintomática, comparada ao placebo e medicações disponíveis no SUS, no tratamento de crianças e adolescentes com TDAH? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews). Resultados: Foram selecionadas 3 revisões sistemáticas, que atenderam aos critérios de inclusão. Conclusão: Lisdexanfetamina e metilfenidato são mais eficazes que placebo, e similares entre si, para reduzir sintomas em escalas de avaliação. Lisdexanfetamina e metilfenidato têm risco similar ao placebo de abandono do tratamento devido a efeitos adversos. Bupropiona não é mais eficaz que placebo para alívio sintomático. Lisdexanfetamina tem efeitos adversos de redução do apetite e insônia/ dificuldades do sono. Não foram encontradas evidências na literatura sobre os efeitos terapêuticos de amitriptilina, clomipramina e nortriptilina no tratamento de crianças e adolescentes com TDAH

Lisdexamfetamine and drugs available in the Brazilian Public Health System (BPHS) (methylphenidate, bupropion, amitriptyline, clomipramine, nortriptyline, bupropion). Indication: Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Question: Lisdexamfetamine is effective and safe for symptomatic improvement, compared to placebo and drugs available in the BPHS, for treatment of children and adolescents with ADHD? Methods: Rapid response review of evidence (overview) of systematic reviews, with bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews). Results: 3 systematic reviews met the inclusion criteria and were selected. Conclusion: Lisdexamfetamine and methylphenidate are more effective than placebo, and similar to each other, to reduce symptoms on rating scales. Lisdexamfetamine and methylphenidate are not different from placebo in the risk of treatment discontinuation due to adverse effects. Bupropion is no more effective than placebo for symptomatic relief. Lisdexamfetamine has adverse effects of decreased appetite and insomnia/sleep troubles. No evidence was found in the literature about therapeutic effects of amitriptyline, clomipramine and nortriptyline for treatment of children and adolescents with ADHD

El rol de los suplementos vitamínicos en pacientes con depresión / The role of vitamin supplements in patients with depression

La depresión es un trastorno del estado de ánimo que se caracteriza por la existencia de un sentimiento de tristeza lo suficientemente intenso como para interferir en el desarrollo de las actividades habituales. A partir de un caso clínico real, en el que una paciente con depresión solicita a su médico de cabecera sumar un suplemento de vitaminas a su plan terapéutico, revisamos la evidencia disponible sobre el uso de estos micronutrientes para el tratamiento de la depresión, y encontramos que no existen pruebas robustas que avalen la suplementación vitamínica en pacientes con este problema de salud. (AU)

Depression is a mood disorder characterised by the existence of a feeling of sadness intense enough to interfere with the performance of normal activities. Based on a real clinical case, in which a patient with depression asked her family doctor to add a vitamin supplement to her therapeutic plan, we reviewed the available evidence on the use of these micronutrients for the treatment of depression and found that there is no robust evidence to support vitamin supplementation in patients with this health problem. (AU)

Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial

Objective: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. Methods: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. Results: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. Conclusion: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. Clinical trial registration: Brazilian Register of Clinical Trials, RBR-5rz5ch

Evaluación del consumo en antidepresivos en la población uruguaya entre 2010 y 2014 / Evaluation of antidepressant use in the Uruguayan population between 2010 and 2014 / Avaliação do uso de antidepressivos na população uruguaia entre 2010 e 2014

Resumen: Objetivo: conocer el consumo de antidepresivos en la población uruguaya en el período 2010-2014. Material y método: se realizó un estudio de utilización de medicamentos para evaluar el consumo de antidepresivos utilizando el dato de dispensación de medicamentos de las farmacias de las instituciones participantes. Se utilizó la variable dosis diaria definida (DDD) por 1.000 habitantes/día (DHD). Resultados: se incluyó el 69% de la población uruguaya. Las DHD globales de antidepresivos para los años 2010, 2011, 2012, 2013 y 2014 fueron: 26,49, 29,71, 30,17, 30,79 y 32,55 (promedio en los 5 años: 30,04) siendo el aumento porcentual global en dicho período de 22,88%. Los ISRS fueron el grupo de antidepresivos más consumidos. Sertralina fue el antidepresivo más consumido en los 5 años de estudio (DHD 13,65), y el de mayor aumento porcentual fue duloxetina, seguido por escitalopram. Conclusión: el consumo de antidepresivos a nivel nacional en el período analizado es inferior al constatado en otros países, con una tendencia al aumento. Éste puede ser visto como una señal para la evaluación evolutiva en el periodo 2015-2020 y para realizar análisis de las prácticas de prescripción y actuales indicaciones, utilizando otras metodologías como los estudios de prevalencia o estudios de indicación-prescripción o de prescripción-indicación.

Abstract: Objective: to learn about antidepressant use in the Uruguayan population between 2010 and 2014. Method: the use of drugs was studied to evaluate the consumption of antidepressants by analysing the dispensing of drugs in the pharmacies that are part of the participating institutions. The study used the defined daily dose variable (DDD) by 1.000 inhabitants/day (DHD). Results: 69% of the Uruguayan population was included in the study. The global antidepressant dose by inhabitants per day for 2010, 2011, 2012, 2013 and 2014 was 26,49, 29,71, 30,17; 30,79 and 32,55 respectively (average in the five years 30,4) being the global increase of percentage 22,88%5 for that period. The SSRIs (selective serotonin reuptake inhibitor) were the most widely used group of antidepressants. Sertraline was the antidepressant of greatest consumption in the 5 years of the study (DHD 13,65), and the one that presented the highest percentage increase was duloxetine, followed by escitalopram. Conclusion: antidepressant use at the national level during the period analysed is lower than that seen in other countries, although a tendency to increase was found. This may be interpreted as a sign for the need to evaluate the evolution in the 2015-2020 period, and to conduct studies on prescription practices and current indications using other methodologies, such as prevalence studies or indication-prescription or prescription-indication studies.

Resumo: Objetivo: conhecer o consumo de antidepressivos na população uruguaia no período 2010-2014. Material e método: foi realizado um estudo sobre o uso de medicamentos para avaliar o consumo de antidepressivos a partir dos dados de dispensação de medicamentos nas farmácias das instituições participantes. Foi utilizada a variável dose diária definida (DDD) por 1.000 habitantes/dia (DHD). Resultados: 69% da população uruguaia foram incluídas. Os DHDs globais de antidepressivos para os anos de 2010, 2011, 2012, 2013 e 2014 foram: 26,49, 29,71, 30,17; 30,79 e 32,55 (média nos 5 anos, 30,04) sendo o aumento percentual global no referido período de 22,88%. Os inibidores seletivos da recaptação da serotonina foram o grupo de antidepressivos mais amplamente utilizado. A sertralina foi o antidepressivo mais utilizado nos 5 anos do estudo (DHD 13,65), e o que apresentou maior aumento percentual foi a duloxetina, seguida do escitalopram. Conclusão: o consumo de antidepressivos em nível nacional no período analisado é inferior ao encontrado em outros países, com tendência de aumento. Isto pode ser visto como um sinal para a avaliação evolutiva no período 2015-2020 e para a realização de análises das práticas de prescrição e indicações atuais, utilizando outras metodologias como estudos de prevalência ou estudos de indicação-prescrição ou prescrição-indicação.

How can we improve antidepressant adherence in the management of depression? A targeted review and 10 clinical recommendations

Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring).

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction / 神经科学通报·英文版

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

Suspensión de la lactancia materna durante el tratamiento de la depresión postparto con sertralina: una revisión bibliográfica / Suspension of breastfeeding during treatment of postpartum depression with sertraline: a literature review

La Organización Mundial de la Salud recomienda amamantar a los recién nacidos, pero resulta contraproducente si la madre presenta una enfermedad que afecte este proceso natural, como la depresión postparto (DPP), una complicación psiquiátrica frecuente en el puerperio que influye en la salud de la madre y del lactante. El tratamiento farmacológico consiste en la administración de antidepresivos, considerándose los riesgos y ventajas, algunos ISRS se destacan por su menor detección en la leche materna; por ello la Sertralina puede ser el más seguro, el lactante ingiere cantidades pequeñas y generalmente no se detectan en el plasma. También se requiere de consejería por la incertidumbre de continuar o no amamantando.

The World Health Organization recommends breastfeeding newborns,but it is counterproductive if the mother presents a disease that affects this natural process, such as possible acute or chronic pathologies in the life cycle of pregnancy, as well as in lactation; one of them is postpartum depression (PPD), a frequent psychiatric complication in the puerperium that influences the health of the mother and the infant, such as early interruption or continued breastfeeding. Pharmacological treatment consists of the administration of antidepressants, considering the risks and advantages, some SSRIs stand out for their lower detection in breast milk; for this reason Sertraline may be the safest, the infant ingests small amounts and is generally not detected in the plasma. It is also the most used during lactation according to most researchers. Mothers may need breastfeeding counseling due to the uncertainty of continuing or not breastfeeding

Guía de práctica clínica para el tamizaje y manejo del episodio depresivo leve en el primer nivel de atención del Seguro Social del Perú (EsSalud) / Clinical practice guideline for the screening and management of the mild depressive episode at the first level of care for the Peruvian Social Security (EsSalud)

El presente artículo resume la guía de práctica clínica (GPC) para el tamizaje y el manejo del episodio depresivo leve en el primer nivel de atención en el Seguro Social del Perú (EsSalud). Para el desarrollo de esta GPC, se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas clínicos y metodólogos, el cual formuló 06 preguntas clínicas. Para responder cada pregunta se realizó búsquedas sistemáticas en PubMed y en repositorios de GPC, y se seleccionó la evidencia pertinente. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones periódicas, el GEG usó la metodología GRADE para revisar la evidencia y emitir las recomendaciones. Se emitieron siete recomendaciones (tres fuertes y cuatro condicionales), 28 puntos de buena práctica clínica, y dos flujogramas.

This paper summarizes the clinical practice guide (CPG) for the screening and management of mild depressive episode at the first level of care in the Social Security of Peru (EsSalud). A guideline development group (GDG) was established for develop this CPG, which included clinical and methodology specialists, who formulated 06 clinical questions. Systematic searches were conducted in Pubmed and GPC repositories to answer each question, and relevant evidence was selected. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GDG used the GRADE methodology for reviewing the evidence and for developing recommendations. At the end, this CPG formulated 07 recommendations (03 strong and 04 conditional), 28 points of good clinical practice, and 02 flow charts were formulated.

Uso de criterios y guías clínicas en la creación de una unidad de trastornos del ánimo / Use of criteria and clinical guidelines in the creation of a mood disorders unit

Los trastornos del ánimo (uni o bipolares) constituyen un significativo problema de salud pública, tanto por su alta prevalencia como por el elevado índice de discapacidad que generan. El presente artículo aborda el problema de la resistencia a tratamiento como también las estrategias y guías clínicas para el manejo de los cuadros de mayor complejidad. Se analizan los aportes de la terapia farmacológica, de la psicoterapia y de las terapias somáticas no farmacológicas, intentando un enfoque integrativo. El equipo multidisciplinario de la Unidad de Trastornos del Ánimo del Departamento de Psiquiatría de Clínica Las Condes busca aplicar un modelo integrativo con una mirada amplia, con el objetivo de encontrar el mejor manejo para cada paciente, orientado no solo a la remisión sintomática sino también a la recuperación funcional (autonomía, calidad de vínculos, etc.), para incidir de este modo en la calidad de vida global de los pacientes.

Affective disorders (uni­ or bipolar) represent a significant public health issue, due both to its high prevalence as well as the high index of disability that they generate. This article addresses the problem of treatment resistance, as well the use of clinical guidelines and strategies for the treatment of more complex cases. We analyze the contributions of pharmacological treatments, psychotherapy and non-pharmacological somatic therapies, from an integrative point of view. The multidisciplinary team of Mood Disorders Unit at Clínica Las Condes Psychiatry Department seeks to apply a broad-view integrative model with the aim of finding the better management strategy for each patient. Our objectives are both symptomatic remission and functional recovery (autonomy, quality of affective bonds, etc.), in order to make a difference on the patients' overall quality of life.

Disfunción tiroidea y trastornos del ánimo: revisión del estado del arte / Thyroid dysfunction and mood disorders: review of the state of the art

La relación entre función tiroidea y trastornos del ánimo se ha observado desde hace más de 50 años. Las hormonas tiroideas, actúan en el cerebro modulando génicamente proteínas asociadas a la fisiopatología de los trastornos del ánimo y potenciando los sistemas de neurotransmisión serotoninérgica y noradrenérgica. En el tratamiento de un episodio depresivo, la normalización de hormonas tiroideas es fundamental, y debe realizarse en todo paciente con sintomatología anímica, especialmente en aquellos con respuestas insuficientes a tratamiento, que requieren niveles de hormonas más estrictos que lo recomendado para población general. En pacientes eutiroideos, la potenciación con triyodotironina ha sido probada, pero también se ha utilizado T4 en altas dosis en casos resistentes, en que se postula que pudiese existir un estado de resistencia a hormonas tiroideas, no reflejado en los niveles hormonales periféricos evaluados rutinariamente. Las enzimas deiodasas, el receptor de hormona tiroidea, y el transportador de hormona tiroidea en la barrera hematoencefálica son blancos a investigar. Los objetivos de la presente revisión son ofrecer orientaciones respecto del uso de hormonas tiroideas en pacientes con trastornos del ánimo, una puesta al día sobre la relación entre hormonas tiroídeas y sistema nervioso central, y las interacciones entre psicofármacos y función tiroidea.

The relationship between thyroid function and mood disorders has been observed for more than 50 years. Thyroid hormones act in the brain genetically modulating proteins associated with the pathophysiology of mood disorders and potentiating the serotonergic and noradrenergic neurotransmission systems. In the treatment of a depressive episode, the normalization of thyroid hormones is essential, and should be performed in all patients with mood symptoms, especially in those with insufficient responses to treatment, which require more stringent hormone levels than recommended for the general population. In euthyroid patients, potentiation with triiodothyronine has been proven, but T4 has also been used in high doses in resistant cases, in which it is postulated that there might be a state of resistance to thyroid hormones, not reflected in the peripheral hormonal levels evaluated routinely. The enzymes deiodasas, the thyroid hormone receptor, and the thyroid hormone transporter in the blood brain barrier are white to investigate. The objectives of this review are to provide guidance regarding the use of thyroid hormones in patients with mood disorders, an update on the relationship between thyroid hormones and central nervous system, and the interactions between psychoactive drugs and thyroid function.

La relación entre la obesidad y estados depresivos / The relationship between obesity and depressive states

La depresión y la obesidad son patologías altamente prevalentes y corresponden a los principales problemas de salud pública. Estas patologías tienen un gran impacto en la morbilidad y mortalidad de los pacientes y afectan la salud y el bienestar de quienes las padecen, así como también afectan en el aspecto socioeconómico consecuencia del deterioro funcional y el gasto de recursos en salud ocasionados. Resultados de estudios epidemiológicos, ensayos clínicos y meta-análisis apoyan la asociación entre los estados depresivos y la obesidad, ya que ambos ocurren conjuntamente en todas las razas de poblaciones evaluadas. El objetivo es abordar la evidencia con respecto a 4 aspectos: (1) obesidad y respuesta a los antidepresivos, (2) trastornos depresivos y su impacto sobre la progresión de la obesidad, (3) tratamiento de la obesidad y el impacto sobre los resultados entre pacientes con trastornos depresivos, (4) el tratamiento de los trastornos depresivos y su impacto sobre los resultados de la obesidad. La evidencia existente apoya la asociación entre obesidad y los resultados adversos para la salud en individuos con trastornos depresivos. Además, destaca el concepto que el tratamiento de una de las dos enfermedades (obesidad o trastornos depresivos) es relevante para mejorar el curso de la otra patología. Puede ser beneficioso explorar dirigidamente la presencia de un trastorno depresivo en sujetos con sobrepeso u obesidad, así como el aumento de peso en personas con depresión. Conocer el efecto de los fármacos antidepresivos sobre el peso corporal es también relevante para facilitar la adherencia al tratamiento en el largo plazo.

Depression and obesity are highly prevalent illness and a mayor public health concern. These diseases have a great impact on morbidity and mortality of patients and affect the health and well-being of those who suffer them, as well as being affected in the socioeconomic aspect as a result of the functional deterioration and the spending of resources. Results of epidemiological studies, clinical trials and meta-analysis support the association between mood disorders and obesity, since both occur together in all the populations evaluated. The objective is to address the evidence regarding four aspects: (1) obesity and response to antidepressants, (2) depressive disorders and their effect on the progression of obesity, (3) treatment of obesity and the effect on outcomes among patients with depressive disorders, (4) the treatment of depressive disorders and their effect on obesity outcomes. Existing evidence supports the association between obesity and adverse health outcomes in individuals with depressive disorders. In addition, it highlights the concept that the treatment of one of the two diseases (obesity or depressive disorders) is relevant to improve the course of the other disease. It may be beneficial to explore the presence of a depressive disorders in overweight or obese subjects, as well as weight gain in subjects with depression. Knowing the effect of antidepressant drugs on body weight is relevant to facilitate adherence to long-term treatment.