Análisis del conocimiento sobre los inhibidores selectivos de la recaptura de serotonina (ISRS) en el manejo de la depresión por médicos residentes y concurrentes de clínica médica de 5 hospitales de CABA / Review of the Knowledge on Selective Serotonin Reuptake Inhibitors (SSRIs) for Depression Management by Resident and Intern Physicians of the Medical Clinic of 5 Hospitals in CABA

Introducción: la depresión es un trastorno cada vez más prevalente alrededor del mundo. Los médicos generales son los profesionales de la salud más consultados por pacientes deprimidos. Más del 70% de los pacientes con depresión son vistos por médicos generales y no por especialistas en Psiquiatría. Según estudios realizados en Buenos Aires, más del 25% de los pacientes internados en Servicios de Clínica Médica en hospitales generales presenta depresión. Estos pacientes suelen ser atendidos y seguidos por médicos en formación, sean residentes o concurrentes de Clínica Médica. El objetivo del trabajo fue analizar el conocimiento sobre los inhibidores selectivos de la recaptura de serotonina (ISRS) que tienen los médicos residentes y concurrentes de Clínica Médica de 5 hospitales de la Ciudad Autónoma de Buenos Aires (CABA) y describir el tratamiento de un paciente depresivo por ellos. Material y métodos: se realizó un estudio descriptivo de corte transversal con un muestreo de tipo no probabilístico. Se utilizó como instrumento de medición un cuestionario semiestructurado organizado en dos secciones, una de datos demográficos que permiten caracterizar la muestra. La otra, de 15 ítems, explora los conocimientos sobre los ISRS y el tratamiento de la depresión. Dicho cuestionario fue revisado por 4 expertos. El instrumento es anónimo. Se aplicó a 59 médicos en formación en Clínica Médica, residentes y concurrentes, de 5 hospitales de la CABA, que participaron de forma voluntaria, durante el período agosto-septiembre de 2022. Resultados: la mayoría de los médicos en formación en Clínica Médica no tratan cuadros depresivos y, ante un paciente deprimido, solicitan la evaluación por un especialista en Salud Mental. Solo un 6,8% lo medica con un antidepresivo. Más del 75% de la muestra refiere recordar los conocimientos que tiene sobre de los ISRS de la cursada de Farmacología y un 13,6 de la cursada de Psiquiatría en la Facultad de Medicina. Conclusión: se observa un conocimiento deficitario sobre los ISRS en médicos residentes y concurrentes de Clínica Médica. Se considera necesario reforzar la formación sobre depresión y manejo de antidepresivos durante la residencia/concurrencia de Clínica Médica. (AU)

Introduction: depression is an increasingly common disorder around the world. General practitioners are the most frequently consulted health professionals by depressed patients. More than 70% of all depressed patients receive treatment by general practitioners and not by psychiatric specialists. According to studies conducted in Buenos Aires, more than 25% of all patients admitted to the Clinical Services in public hospitals present depression. These patients are usually under the care and follow-up of clinical trainee physicians, residents, or interns.This study aimed to analyze the knowledge about selective serotonin reuptake inhibitors (SSRIs) of clinical trainee residents and interns in five hospitals in the Ciudad Autónoma de Buenos Aires (CABA) and to describe their treatment of a depressive patient. Material and methods: we conducted a descriptive cross-sectional study with a non-probabilistic sampling. We used a semi-structured questionnaire arranged into two sections as a measuring tool. One, with demographic data to describe the sample. The other, with 15 items, explores respondents' knowledge of SSRIs and the treatment of depression. Four experts reviewed the questionnaire, which was anonymous. We applied it to 59 clinical medical trainees, residents, and interns from five CABA hospitals who volunteered to participate during August-September 2022. Results: most clinical trainees do not treat depressive conditions and, when confronted with a depressed patient, request an assessment by a Mental Health specialist. Only 6.8% medicate the patient with an antidepressant. More than 75% of the sample reported remembering their knowledge of SSRIs from the Pharmacology course and 13.6% from the Psychiatry course at the School of Medicine. Conclusion: there is a deficient knowledge about SSRIs in trainee residents and interns of Clínica Médica. We believe it is necessary to reinforce training on depression and management of antidepressants during residency/internship practice in Clínica Médica. (AU)

Diretrizes clínicas para tratamento da depressão: análise de fatores associados à qualidade e comparação de recomendações para pacientes não respondedores e com depressão resistente / Clinical guidelines for the treatment of depression: analysis of factors associated with quality and comparison of recommendations for nonresponding patients and for patients with resistant depression

Diretrizes clínicas (DCs) de alta qualidade são importantes para a assistência efetiva de pacientes com doenças crônicas, incluindo a depressão. A depressão é um dos principais problemas de saúde mundial, sendo um dos transtornos psiquiátricos mais comumente encontrados na prática médica, afetando cerca de 300 milhões de pessoas. Além de sua natureza debilitante e onerosa, muitas vezes pode levar a desfechos graves, tal como o suicídio, principalmente em pacientes que não respondem aos tratamentos. Assim, o objetivo geral desta tese foi identificar fatores das DCs associados à qualidade metodológica desses documentos e de suas recomendações, e comparar as recomendações para duas situações de falhas da farmacoterapia: pacientes não respondedores e pacientes com depressão resistente ao tratamento (DRT). Operacionalmente, foram feitas revisões sistemáticas da literatura em bases científicas e específicas de DCs, e incluídas DCs publicadas nos últimos onze anos que contivessem recomendações para o tratamento farmacológico de adultos com depressão. Para avaliação geral das DCs, foi aplicado o instrumento AGREE II, e para avaliação específica das recomendações, o instrumento AGREE-REX. As DCs foram consideradas de alta qualidade quando pontuaram com escores maiores ou iguais a 60% (no estudo descrito no capítulo 2) e maiores ou iguais a 80% (no estudo descrito no capítulo 3) no domínio 3 (Rigor de desenvolvimento) do AGREE II. As DCs com recomendações de alta qualidade foram as que pontuaram com mais de 60% no domínio 1 (Aplicabilidade Clínica) do AGREE-REX. Das 63 DCs selecionadas, 17 (27%) apresentaram alta qualidade, e 7 (11%) apresentaram recomendações de alta qualidade. Os fatores associados à maior qualidade foram gerenciamento de conflitos de interesses, equipe multiprofissional e tipo de instituição. A inclusão de representante do paciente na equipe também foi associada a recomendações de maior qualidade. Verificou-se que a maioria das DCs concorda com a necessidade de: reavaliar o diagnóstico, a presença de comorbidades, a adesão ao tratamento, ajustar a dosagem do antidepressivo e adicionar psicoterapia como os primeiros passos para aqueles que não respondem ao tratamento antidepressivo de primeira linha. Em relação às recomendações, há falhas importantes, incluindo a não apresentação de definição padronizada de resposta adequada/inadequada/parcial, e o não estabelecimento de tempo de tratamento necessário para declarar DRT. Todas as DCs incluíram a possibilidade de substituição do antidepressivo, potencialização com outros medicamentos e combinação de antidepressivos. Todavia, três DCs não recomendaram uma sequência entre eles. Por fim, verificou-se que das 17 DCs de alta qualidade e das 7 DCs com recomendações de alta qualidade, apenas duas incluíram definição e recomendações para DRT. Não existe consenso entre as DCs de alta qualidade quanto à definição e uso do termo DRT. Não foi possível extrair uma estratégia terapêutica convergente para DRT em adultos. Os resultados obtidos reforçam a necessidade de maior foco no aprimoramento da qualidade das DCs e de suas recomendações, especialmente nos subgrupos relativos à resposta inadequada ao tratamento e a DRT, nas quais as definições não são claras

High-quality clinical practice guidelines (CPGs) are important for treating patients with chronic diseases such as depression. Depression is a major health concern worldwide, affecting approximately 300 million people. It is one of the most prevalent psychiatric disorders in medical practice. It is not only debilitating and costly but can also lead to tragic consequences such as suicide, particularly in patients who do not respond to treatment. The objective of this thesis was to identify CPGs factors associated with the methodological quality of these documents and their recommendations. Furthermore, this thesis aimed to compare the recommendations in two pharmacotherapy failure situations: inadequate response to treatment and treatment-resistant depression (TRD). Systematic literature reviews were conducted on scientific and CPG-specific databases. Reviews were also conducted on CPGs published in the last eleven years that included recommendations for pharmacological treatment of adults with depression. The AGREE II instrument was used for the CPGs general assessment, while the AGREE-REX instrument was used specifically to assess their recommendations. CPGs were considered high quality if they achieved a score of at least 60% in the study mentioned in Chapter 2 and a score of at least 80% in the study mentioned in Chapter 3 in the AGREE II, rigour of development domain. The CPGs with high-quality recommendations were those that scored greater than 60% in Domain 1 (Clinical Applicability) of the AGREE-REX. Of the 63 selected CPGs, 17 (27%) were high quality, and 7 (11.1%) had recommendations of high quality. Factors associated with higher quality were conflict of interest management, multi-professional team, and type of institution. Inclusion of a patients representative on the team was associated with higher quality recommendations. Most CPGs agreed with the need to reassess diagnoses, comorbidities, and treatment adherence. They also agreed on adjusting antidepressant dosage and providing psychotherapy as a first step for patients who do not respond to first-line antidepressant treatment. There are significant shortcomings in the recommendations. In particular, the lack of a standardized definition of adequate, inadequate, or partial response to treatment and the lack of clarity surrounding the duration of treatment required to establish TRD. All CPGs included the possibility of antidepressant substitution, potentiation with other drugs, and a combination of antidepressants. However, three CPGs did not recommend a preferred sequence for these interventions. Finally, of the 17 high-quality CPGs and the 7 CPGs with high-quality recommendations, only two included definition and recommendations for TRD. There is no consensus among the high-quality CPGs regarding the definition and use of the term TRD. Ultimately, finding a convergent therapeutic strategy for TRD in adults was not possible. These results highlighted the need to focus more on improving the quality of CPGs and their recommendations, especially in the subgroups related to inadequate response to treatment and TRD, where definitions are unclear

Adjunctive vortioxetine for SSRI-resistant major depressive disorder: a real-world chart review study

Objective: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. Methods: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression ‐ Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). Results: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). Conclusions: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial

Objective: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). Methods: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. Results: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). Conclusion: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. Clinical trial registration: ACTRN12612000283875.

Pattern evolution of antidepressants and benzodiazepines use in a cohort

ABSTRACT OBJECTIVE In recent decades there has been an increase in the use of antidepressants (AD) and a decrease in the use of benzodiazepines (BDZ). Prevalence, cumulative incidence, and factors associated with the incidence of AD and BDZ use in a Brazilian population were estimated in this article. METHODS Data were collected with a self-administered questionnaire in a cohort of employees from a university in Rio de Janeiro. The prevalence of the use of AD and BDZ was calculated for 1999 (4,030), 2001 (3,574), 2006-07 (3,058), and 2012 (2,933). The cumulative incidences of the use of AD and BDZ between 1999 and 2007 were estimated by the Poisson models with robust variance estimates. RESULTS In 1999, the prevalence of the use of AD and BDZ were 1.4% (95%CI: 1.1-1.8) and 4.7% (95%CI: 4.1-5.4), respectively; in 2012, they were 5.4% (95%CI: 5.5-6.2) and 6.8% (95%CI: 6.0-7.8). The incidence of use, between 1999 and 2007, was 4.9% (95%CI: 4.2-5.7) for AD and 8.3% (95%CI: 7.3-9.3) for BDZ. The incidences of AD and BDZ use were higher among women and participants with a positive General Health Questionnaire. CONCLUSION In this population, the increase in the use of AD was not accompanied by a decrease in the use of BDZ, showing the prescriptions for psychotropic medication do not follow the currently recommended guidelines for treatment of common mental health disorders.

La depresión: un desafío en la práctica médica general / La depresión: un desafío en la práctica médica general

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)

Unavailability of appropriate doses and need for tablet splitting of psychotropic drugs by geriatric patients / Indisponibilidade de doses apropriadas e necessidade de fracionamento de medicamentos psicotrópicos por pacientes geriátricos

BACKGROUND: Tablet splitting appears common in older adults, but its safety, and the factors associated with this practice, remain unclear. OBJECTIVE: To identify which psychotropic drugs are most often split, which doses are intended with this practice, and whether these doses are provided by the Brazilian Unified Health System (SUS) or commercially available. METHODS: Cross-sectional descriptive study of 632 geriatric outpatients. The number of individuals who split tablets was identified, as well as the psychotropic drugs they used and split. The availability of these drugs on the SUS network and on the market was assessed by checking the 2017 National Formulary of Essential Medicines (RENAME 2017) and the Dictionary of Proprietary Medicinal Products (Dicionário de Especialidades Farmacêuticas) respectively. RESULTS: Tablet splitting was reported by 178 patients (28.2%). This practice was significantly more common among those aged 80 years or older. Tablet splitting was significantly associated with a greater number of medical visits and a higher pill burden. The most commonly affected therapeutic classes were antipsychotics (23.9%), other psychotropic drugs (18.7%) and antidepressants (12.3%). Of the 20 psychotropic drugs split, 45% were available on the SUS. CONCLUSIONS: Tablet splitting poses a challenge, as there is no guarantee of uniformity of concentration of the active ingredient in the split halves. Although the psychotropic drugs that were split in this sample are commercially available, most were not available from SUS in the desired dose forms for older adults.

INTRODUÇÃO: O fracionamento de comprimidos é comum em pacientes geriátricos, mas a segurança e os fatores associados a essa prática permanecem incertos. OBJETIVO: Identificar quais medicamentos psicotrópicos são mais frequentemente fracionados, quais doses se destinam a essa prática e se essas dosagens são fornecidas pelo Sistema Único de Saúde (SUS) ou comercialmente disponíveis. MÉTODOS: Estudo descritivo transversal de 632 pacientes ambulatoriais geriátricos. O número de indivíduos que fracionou os comprimidos foi identificado, bem como os medicamentos psicotrópicos que foram usados e fracionados. A disponibilidade desses medicamentos na rede SUS e no mercado foi avaliada através da verificação do Formulário Nacional de Medicamentos Essenciais (RENAME) de 2017 e do Dicionário de Especialidades Farmacêuticas, respectivamente. RESULTADOS: A partição de comprimidos foi relatada por 178 pacientes (28,2%). Essa prática foi significativamente mais comum entre aqueles com 80 anos ou mais. O fracionamento dos comprimidos foi significativamente associado a um maior número de consultas médicas e a uma maior carga de comprimidos. As classes terapêuticas mais comumente afetadas foram antipsicóticos (23,9%), outros medicamentos psicotrópicos (18,7%) e antidepressivos (12,3%). Dos 20 medicamentos psicotrópicos fracionados, 45% estavam disponíveis no SUS. CONCLUSÕES: O fracionamento de comprimidos representa um desafio, pois não há garantia de uniformidade de concentração do ingrediente ativo nas metades fracionadas. Embora os medicamentos psicotrópicos fracionados nesta amostra estejam disponíveis comercialmente, a maioria não estava disponível no SUS nas formas de dosagem desejadas para a população geriátrica.

Acute effects of ayahuasca in a juvenile non-human primate model of depression

Objective: The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression. Methods: While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight. Results: After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects. Conclusions: These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.

Overactive bladder - pharmacological treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Medición de la concordancia en la elección de antidepresivos entre psiquiatras costarricenses que no aplican y sí aplican el algoritmo de razonamiento psicofarmacológico / Measurement of the concordance in the selection of antidepressants between costarican psychiatrists that do not apply and apply the Psychopharmacological Reasoning Algorithm

Resumen Justificación: existe una alta comorbilidad entre las enfermedades médico-quirúrgicas y la depresión. No hay parámetros sistematizados que guíen la selección individualizada del tratamiento farmacológico en estas circunstancias. Objetivo: analizar la concordancia entre los psiquiatras costarricenses que no aplican y sí aplican el algoritmo de razonamiento psicofarmacológico para la elección de los antidepresivos, en 3 casos clínicos de pacientes deprimidos y con una enfermedad médico-quirúrgica. Metodología: se distribuyó de forma aleatoria en dos grupos a los participantes, y se les presentó tres casos clínicos reales y anónimos de personas deprimidas y con una enfermedad médico-quirúrgica. El grupo A eligió el antidepresivo según sus criterios personales, mientras que el grupo B realizó la elección del tratamiento basándose en la implementación del algoritmo de razonamiento psicofarmacológico. Resultados: no hubo concordancia respecto al fármaco entre los 22 psiquiatras del grupo que solo aplicó el criterio clínico (kappa= -0,0154, p= 0,3851), mientras que la concordancia sí fue estadísticamente significativa en el grupo de los 24 psiquiatras que aplicó el algoritmo de razonamiento psicofarmacológico (kappa=0,016, p<0,01). La concordancia entre ambos grupos fue del 25 % en el caso 1, el 16,67% en el caso 2 y el 20,83% en el caso 3. Los psiquiatras que emplearon el algoritmo de razonamiento psicofarmacológico lo consideran útil (87,50%), aplicable (83,33%) y con posible impacto clínico (91,67%). Conclusiones: el algoritmo de razonamiento psicofarmacológico aumentó la concordancia entre los psiquiatras para la selección de los antidepresivos en tres casos clínicos de pacientes deprimidos con enfermedades médico-quirúrgicas, en comparación con el criterio personal. La concordancia entre los grupos A y B fue muy baja. El algoritmo de razonamiento psicofarmacológico es una herramienta considerada útil, aplicable y de posible impacto en la práctica clínica.

Abstract There is a high comorbidity between medical surgical diseases and depression. There is no current systematic approach to guide how to select an individualized treatment under these circumstances. Objective: to analyze the concordance between psychiatrist that do not use and those who use the Psychopharmacological Reasoning Algorithm to choose the treatment for 3 clinical cases of depression and medical surgical diseases. Methodology: Three case vignettes of anonymous real depressed patients with medical surgical diseases were presents to both groups. Group A made the selection of the antidepressant using their personal criteria; group B made the selection applying the Psychopharmacological Reasoning Algorithm. Results: There was no concordance on the drug among the 22 psychiatrists in the group that only applied the clinical criterion (kappa = -0.0154, p = 0.3851), whereas concordance was statistically significant in the group of 24 psychiatrists who applied the Psychopharmacological Reasoning Algorithm (kappa = 0.016, p <0.01). The concordance between groups A and B was 25% in the case 1, 16.67% in the case 2 and 20.83% in the case 3. The biggest majority of the psychiatrist that used the PPRA considers it useful (87.50%), applicable (83.33%) and with the possibility of impact the clinical practice (91.67%). Conclusion: The Psychopharmacological Reasoning Algorithm increased the concordance in the selection of antidepressants made by Costa Rican psychiatrists in 3 clinical vignettes of depressed patients with a medical surgical disease, when compared to personal criteria. The concordance in the selection of the antidepressants in the 3 cases between both groups is low. The Psychopharmacological Reasoning Algorithm is a tool considered useful, applicable and with a possible impact in clinical practice.

Uso de medicamentos antidepressivos na amamentação: avaliação da conformidade das bulas com fontes bibliográficas baseadas em evidências científicas / Use of antidepressants during breastfeeding: evaluating drug package inserts conformity with science-based bibliographical sources / Uso de medicamentos antidepresivos durante la lactancia: evaluación de la conformidad de los prospectos, respecto a fuentes bibliográficas basadas en evidencias científicas

O objetivo deste artigo foi avaliar a conformidade entre as recomendações de uso de medicamentos antidepressivos durante a amamentação, presentes em bulas, e as recomendações de fontes bibliográficas baseadas em evidências científicas. Foram avaliadas as bulas padrão de 23 antidepressivos com registro ativo no Brasil. A presença de contraindicação do uso do antidepressivo durante a amamentação foi comparada com as informações presentes no manual técnico do Ministério da Saúde, no livro Medications and Mothers' Milk e nas bases de dados LactMed, Micromedex e UpToDate. Na maioria das bulas (62,5%), o antidepressivo é contraindicado na amamentação. Entre as fontes bibliográficas, esse percentual variou de 0% a 25%. O estudo aponta para baixa conformidade entre bulas e fontes bibliográficas, alertando sobre a necessidade de revisão do conteúdo e forma de apresentação das informações presentes nas bulas dos antidepressivos no Brasil.

This article sought to evaluate the conformity between recommendations regarding antidepressant use during breastfeeding found in drug package inserts with recommendations from science-based bibliographic sources. We evaluated the standard drug package inserts of 23 antidepressants with active registration in Brazil. The presence of contraindications of antidepressant use during breastfeeding was compared with information present in the Brazilian Ministry of Health technical manual, the book Medications and Mothers' Milk and on the databases LactMed, Micromedex and UpToDate. In most drug package inserts (62.5%), antidepressants are contraindicated during breastfeeding. Among bibliographical sources, that percentage varied between 0% and 25%. The study shows a low conformity between drug package inserts and bibliographical sources, alerting to the need for revising the content and presentation of information present in antidepressant drug package inserts in Brazil.

El objetivo de este artículo fue evaluar la conformidad entre las recomendaciones de uso de medicamentos antidepresivos durante la lactancia, presentes en prospectos, y las recomendaciones de fuentes bibliográficas, basadas en evidencias científicas. Se evaluaron los prospectos estándar de 23 antidepresivos con registro activo en Brasil. La presencia de contraindicaciones en el consumo de antidepresivos durante la lactancia se comparó con la información presente en el manual técnico del Ministerio de la Salud, en el libro Medications and Mothers' Milk, y en las bases de datos LactMed, Micromedex y UpToDate. En la mayoría de los prospectos (62,5%), el antidepresivo está contraindicado durante la lactancia. Entre las fuentes bibliográficas el porcentaje varió de 0% a 25%. El estudio señala la escasa conformidad entre prospectos y fuentes bibliográficas, alertando sobre la necesidad de revisión del contenido, así como de la forma de presentación de la información que aparece en los prospectos de los antidepresivos en Brasil.

Consumo de drogas médicas, medicamentos de venta libre y alcohol en adultos mayores / Consumption of medical drugs, over-the-counter medications and alcohol in elderlys / Consumo de drogas médicas, medicamentos de venda livre e álcool em idosos

Objetivo: realizar una revisión sistemática de la literatura para identificar los estudios que reportan la frecuencia del consumo drogas médicas, medicamentos de venta libre y alcohol, así como el consumo combinado de estas sustancias en los adultos mayores. Método: se utilizó como guía la Preferred Reporting Items for Systematic Reviews and Meta-Analyses, se identificaron 4,881 artículos a través de las bases de datos y tres artículos en el buscador google scholar, se eligieron doce estudios ya que cumplieron con los criterios de elegibilidad y por su calidad metodológica. Resultados: la revisión de la literatura permitió identificar que las drogas médicas más utilizadas fueron los benzodiacepinas, los sedantes, los antidepresivos y los psicotrópicos, los medicamentos de venta libre más usados fueron los analgésicos, laxantes, antiácidos y antihistamínicos; la combinación con el alcohol son prácticas observadas entre los adultos mayores. Conclusión: las drogas médicas y medicamentos de venta libre son consumidas para tratar los trastornos del sueño, depresión, ansiedad y estrés; con relación al alcohol entre el 20.3% y el 57.1% de los adultos mayores lo consumen; la combinación de alcohol y drogas médicas se observó entre el 9.3% y el 18.1%.(AU)

Objective: to perform a systematic review of the literature to identify the studies that report the frequency of consumption of medical drugs, over-the-counter medications and alcohol, as well as the combined use of these substances in the elderly. Method: the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes were used as a guide, 4,881 items through the databases and three items in the search google scholar were identified, twelve studies were chosen as they met the eligibility criteria and their methodological quality. Results: the literature review allowed us to identify that the most used medical drugs were benzodiazepines, sedatives, antidepressants and psychotropic drugs, the most used over-the-counter medications were analgesics, laxatives, antacids and antihistamines; the combination with alcohol are practices observed among the elderly. Conclusion: medical drugs and over-the-counter medications are consumed to treat sleep disorders, depression, anxiety and stress; in relation to alcohol between 20.3% and 57.1% of the elderly consume it; the combination of alcohol and medical drugs was observed between 9.3% and 18.1%.(AU)

Objetivo: realizar uma revisão sistemática da literatura para identificar os estudos que revelam a frequência do consumo de drogas médicas, medicamentos de venda livre e álcool, assim como o consumo combinado dessas substâncias em idosos. Método: foi utilizada como guia a Preferred Reporting Items for Systematic Reviews and MetaAnalyses, foram identificados 4,881 artigos através das bases de dados e três artigos no Navegador Google Scholar, foram selecionados doze exames já que cumpriram com os critérios de elegibilidade e pela sua qualidade metodológica. Resultados: a revisão da literatura permitiu identificar que as drogas médicas mais utilizadas foram as benzodiazepínicas, sedativos, antidepressivos e os psicotrópicos. Os medicamentos de venda livre mais usados foram os analgésicos, laxantes, antiácidos e anti-histamínicos. A combinação com o álcool é um comportamento observado nos idosos. Conclusão: as drogas médicas e medicamentos de venda livre são consumidos para o tratamento dos distúrbios do sono, depressão, ansiedade e estresse. Com relação ao álcool, entre 20.3% e 57.1% das pessoas idosas o consomem. A combinação de álcool e drogas médicas foi observada entre 9.3% e 18.1%.(AU)

¿Es efectiva la potenciación con folato para el trastorno depresivo mayor? / Is augmentation with folate effective for major depressive disorder?

INTRODUCCIÓN: En una proporción importante de los pacientes con depresión, el tratamiento antidepresivo no lleva a una respuesta satisfactoria. Actualmente se postula que la coadministración de nutrientes estandarizados farmacológicamente (nutracéuticos), como el folato en este caso, podrían potenciar los efectos de los antidepresivos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que en conjunto incluyen nueve estudios primarios, de los cuales, ocho son ensayos aleatorizados. Concluimos que la potenciación con folato en el tratamiento del trastorno depresivo mayor probablemente resulta en poca o nula diferencia en los síntomas depresivos. Pudiese ser interesante evaluar el efecto de formas de presentación específicas del folato o en población con déficit objetivado.

INTRODUCTION: Antidepressant treatment does not lead to a satisfactory response in a significant proportion of patients with depression. It has been postulated that co-administration of pharmacologically standardized nutrients (nutraceuticals), such as folate, would potentiate the effect of antidepressants. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified four systematic reviews including nine studies overall, of which eight were randomized trials. We concluded augmentation with folate for the treatment of major depressive disorder probably results in little or no difference in depressive symptoms. It would be interesting to evaluate the effects of specific presentation forms of folate or in population with objective folate deficit.

Bupropión: una alternativa farmacológica en cesación tabáquica / Bupropion: a pharmacological alternative in smoking cessation

Resumen Hay muchas razones para el uso de antidepresivos en cesación tabáquica: 1) la falta de nicotina puede producir síntomas depresivos o precipitar un episodio depresivo grave; 2) la nicotina puede tener efectos antidepresivos que mantienen la adicción; 3) algunos antidepresivos tienen una acción en vías neuronales o receptores implicados en la adicción a la nicotina; y 4) algunos pacientes no desean usar otras terapias o han fracasado con ellas. Bupropión es terapia de primera línea para la cesación del tabaco, con efectividad a largo plazo, los efectos adversos graves son escasos. La evidencia sugiere que bupropión es de eficacia similar a la terapia de reemplazo de nicotina (TRN) y menos eficaz que vareniclina, pero se necesita más estudios para confirmar esto. Bupropión es seguro en pacientes psiquiátricos compensados en un periodo de tres meses o más.

There are many reasons for the use of antidepressants in smoking cessation: 1) lack of nicotine can produce depressive symptoms or precipitate a severe depressive episode; 2) nicotine may have antidepressant effects that maintain addiction; 3) some antidepressants have an action on neural pathways or receptors involved in nicotine addiction; and 4) some patients do not want to use other therapies or they have failed with them. Bupropion is first-line therapy for smoking cessation, with long-term effectiveness, serious side effects are rare. The evidence suggests bupropion is similar in effectiveness to nicotine replacement therapy (NRT), and less effective than varenicline, but more studies are needed to confirm this. Bupropion is safe in psychiatric patients compensated over a period of three months or more.

Pharmacological treatment and staging in bipolar disorder: evidence from clinical practice

Objectives: Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD. Methods: One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV. Results: Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed. Conclusions: This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness. .

Dispepsia / Dyspepsia

Etmologicamente, a palavra dispepsia (do grego dis = difícil e pepse = digestão) significa digestão difícil. Sob o ponto de vista clínico, corresponde a uma série de sintomas de origem gastroduodenal, como dor, queimação ou desconforto epigástrico, plenitude pós-prandial ou saciedade precoce associadas ou não a náusea, vômitos e distensão em andar superior do abdome. Traduz, pois, um distúrbio funcional ou orgânico, de localização epigástrica e origem gastroduodenal...

Etymologically, the greek word dis means hard and pepse means digestion. Therefore, dyspepsia is a poor digestion. From the clinical point of view, dyspepsia corresponds to a range of symptoms originated from gastroduodenal, like pain, heartburn or epigastric discomfort, postprandial fullness or early fullness related or not to nausea, vomiting, upper abdominal distension. So, this explain that a functional or organic decline situated at the epigastric area and it is originated from gastroduodenal...

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent. .