Rationality for the Use of Neuromodulation in Disorders of Gut-Brain Interaction (Functional Gastrointestinal Disorders)

Within the broad range of therapeutic options for managing functional gastrointestinal disorders, recently redefined as Disorders of Gut-Brain Interaction (DGBI) by the Rome Foundation in the Rome IV criteria, certain medications with antidepressant, anxiolytic, or antipsychotic effects are commonly employed. These drugs, now referred to as neuromodulators by the Rome Foundation, target the neurogastroenterological dysfunction associated with these disorders. Consequently, their clinical utility as psychiatric medications can now be leveraged to benefit patients with DGBI. This narrative review aims to provide an updated and specific overview of the indications for neuromodulators in the primary DGBI. The first section of this review focuses on the rationale and justification for their use.

En el amplio espectro de las opciones terapéuticas para el manejo de los trastornos funcionales digestivos, que se han redefinido por la Fundación Roma en los criterios Roma IV como trastornos de la interacción cerebro-intestino (TICI), algunos medicamentos con efectos antidepresivos, ansiolíticos o antipsicóticos se utilizan con mayor frecuencia. Estos medicamentos, que actúan en la disfunción neurogastroenterológica de estos trastornos, también han sido renombrados por la Fundación Roma como neuromoduladores, para que ahora puedan aprovecharse sus beneficios terapéuticos en este ámbito clínico, debido a su utilización como medicamentos psiquiátricos. Esta revisión narrativa tiene por objeto actualizar y precisar las indicaciones de los neuromoduladores en los principales TICI, y en esta primera sección se aborda la racionalidad y justificación para su utilización.

Molecular basis and mechanism of action of Albizia julibrissin in depression treatment and clinical application of its formulae / 中草药·英文版

Albizzia julibrissin is empirically used as an antidepressant in clinical practice. Preclinical studies have indicated that its total extracts or bioactive constituents exerted antidepressant-like responses in animal models, providing the molecular basis to reveal its underlying mechanism of action. While attempts have been made to understand the antidepressant effect of A. julibrissin, many fundamental questions regarding its mechanism of action remain to be addressed at the molecular and systems levels. In this review, we conclusively discussed the mechanism of action of A. julibrissin and A. julibrissin formulae by reviewing recent preclinical and clinical studies conducted by using depressive animal models and depressive patients. Several representative bioactive constituents and formulae were highlighted as examples, and their mechanisms of action were discussed. In addition, some representative A. julibrissin formulae that have been shown to be compatible with conventional antidepressants in clinical practice were also reviewed. Furthermore, we discussed the future research directions to reveal the underlying mechanism of A. julibrissin at the molecular and systems levels in depression treatment. The integrated study using both the molecular and systematic approaches is required not only for improving our understanding of its molecular basis and mechanisms of action, but also for providing a way to discover novel agents or approaches for the effective and systematic treatment of depression.

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

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).

Implicações neurológicas da meditação do tipo terapia cognitiva baseada em mindfulness em pacientes com transtorno de ansiedade ou transtorno depressivo: uma revisão integrativa / Neurological implications of mindfulness-based cognitive therapy in patients with anxiety or depressive disorders: an integrative review / Implicaciones neurológicas de la meditación de la terapia cognitiva basada en mindfulness en pacientes con trastorno de ansiedad o trastorno depresivo: una revisión integradora

A Terapia Cognitiva Baseada em Mindfulness (MBCT, do inglês Mindfulness-Based Cognitive Therapy) é uma técnica baseada na combinação da Terapia Cognitiva-Comportamental e da meditação mindfulness, na busca pela melhoria de sintomas psiquiátricos. O presente trabalho tem como objetivo a busca por publicações que discutam as implicações neurológicas de pacientes diagnosticados com transtorno depressivo e transtorno de ansiedade e que buscaram nessa técnica a melhoria de sua condição clínica ou qualidade de vida. Nossos resultados preliminares mostraram que os benefícios dessa prática foram colhidos na totalidade dos estudos encontrados, elucidando as áreas cerebrais modificadas e o motivo pelo qual elas foram ativadas. Procuramos abordar ainda a diferença entre essa técnica e o uso de medicamentos e tratamento usual. PALAVRAS-CHAVE: Terapia Cognitiva-Comportamental; Cérebro; Transtornos Psiquiátricos; Antidepressivos.

Mindfulness-Based Cognitive Therapy (MBCT) is a technique based on the combination of Cognitive-Behavioral Therapy and mindfulness meditation, in the search of improving psychiatric symptoms. This present work aims to search for studies and articles that discuss the neurological implications of patients diagnosed with anxiety and major depressive disorders who sought improvement in their clinical condition or life quality through this technique. The preliminary results showed that the benefits of this practice were observed in all of the studies found, elucidating the modified brain areas and the reason why they were activated. The differences between this technique and the use of medication and treatment-as-usual was also addressed.

La Terapia Cognitiva Basada en Mindfulness (MBCT) es una técnica basada en la combinación de la Terapia Cognitivo-Conductual y la meditación mindfulness, en la búsqueda de la mejora de los síntomas psiquiátricos. El presente trabajo tiene como objetivo buscar publicaciones que discutan las implicaciones neurológicas de pacientes diagnosticados con trastorno depresivo y trastorno de ansiedad y que busquen en esta técnica mejorar su condición clínica o calidad de vida. Nuestros resultados preliminares mostraron que los beneficios de esta práctica se cosecharon en todos los estudios encontrados, dilucidando las áreas cerebrales modificadas y la razón por la cual se activaron. También tratamos de abordar la diferencia entre esta técnica y el uso de medicación y tratamiento habitual.

Practical considerations in the pharmacological treatment of bipolar disorder / 四川精神卫生

Bipolar disorder is one of the most common mood disorders characterized by an early age of onset and high prevalence rate， and patients tent to have poor prognosis due to high misdiagnosis rate and incomplete diagnosis rate. At present， existing pharmacological treatment for bipolar disorder remains highly variable. Therefore， this paper presents a review of indications of the medications， clinical therapeutic effect and adverse drug reactions， thus providing references for the pharmaceutical treatment of bipolar disorder.

The speed-limiting role in the onset of antidepres-sants:the re-establishment of the excitation/inhibi-tion(E/I)function balance in the mPFC of rats / 中国药理学与毒理学杂志

OBJECTIVE There are serious hazards in depression,and the precise mechanism underlying the delayed onset of clinical antidepressants remains unclear.The purpose of this study was to investigate the regular pattern of the speed-limiting role of excitation/inhibition(E/I)function balance in the mechanism of antidepressant action.METHODS Based on the previous study,we focused on glutamatergic pyramidal neurons in the medial prefrontal cortex(mPFC)here and used its excitability to represent the establishment of a new E/I functional balance.We studied the changes in the firing activity of glutamatergic pyramidal neuron in the mPFC at different administration times for five types of antidepressants that act on different pharmacological targets and different onset times,including fluoxetine(SSRI),duloxetine(SNRI),vilazodone[serotonin 1A receptor(5-HT1A)ago-nist and SSRI],ketamine[N-methyl-D-aspartate(NMDA)receptor antagonist],and hypidone hydrochloride(YL-0919,new antidepressant with sigma-1 receptor ago-nist and SSRI).We first examined the initial onset time of activation of pyramidal neurons using multichannel elec-trophysiological recordings and tested the antidepressant behavioral effects using the FST.We then selected three antidepressants(fluoxetine,ketamine,and vilazodone)to explore its effects on the BDNF-mTOR pathway by West-ern blotting.In addition,we disrupted the E/I function bal-ance using chemogenetics to investigate the antidepres-sant-like effects of YL-0919 and ketamine in the FST and TST.RESULTS We found that treatment with fluoxetine for 17 days significantly increased the firing activity of pyramidal neurons and decreased the immobility duration in the FST.Similarly,it took duloxetine for 10 d,vilazodone for 4 d,YL-0919 for 3 d and ketamine for 24 h,to exert such effects.Meanwhile,Western blotting results sug-gested that the expression of BDNF and phosphorylation of mTOR in the mPFC significantly increased.How-ever,haloperidol,a classic antipsychotic(without antide-pressant effects),exerted no such effects on the firing activities of pyramidal neurons.In addition,disrupting the E/I function balance(via activating the GABA neurons and inhibiting the glutamate neurons)blocks out the antidepressant-like effects of YL-0919 and ketamine in the FST and TST.CONCLUSION Taken together,our findings suggest that the commencement of antide-pressant effects may be accompanied by the increase in the firing activity of pyramidal neurons and the activation of the BDNF-mTOR pathway,which may be a necessary and rate-limiting process.The re-establishment of the E/I balance may be a landmark event for the onset of antide-pressant effects.

Manejo farmacológico del episodio depresivo bipolar en adolescentes: actualización bibliográfica / Pharmacological management of bipolar depressive episode in adolescents: bibliographic update

El manejo farmacológico del episodio depresivo en contexto del trastorno bipolar constituye un desafío para el clínico tanto en psiquiatría adultos como infantoadolescente. El presente trabajo tiene por objetivo actualizar y sintetizar la evidencia disponible respecto al manejo farmacológico para la depresión bipolar en población pediátrica. Metodología: Se realizó una búsqueda de las publicaciones de los últimos 5 años en bases de datos. Resultados: La evidencia muestra como primera línea el uso de antipsicóticos de segunda generación por sobre los estabilizadores del ánimo en este grupo etario; demostrando lurasidona y lanzapina/fluoxetina eficacia similares. Lurasidona es una opción con mejor perfil de seguridad por asociarse a menos efectos adversos y mejor adherencia. El uso de antidepresivos debe considerarse dentro de los pasos iniciales del manejo, asociado a un antipsicótico de segunda generación. Conclusiones: Se destaca la importancia de la sospecha, evaluación y diagnóstico adecuado para guiar la decisión de manejo integral. A pesar de los riesgos y consideraciones existentes, es importante considerar el uso en primera línea de antipsicóticos de segunda generación y de antidepresivos en el manejo de un cuadro depresivo en contexto de la enfermedad bipolar. La escasez de estudios en el tratamiento farmacológico de la depresión bipolar en general y especialmente en población pediátrica limita la generalización y extrapolación de los resultados a la realidad local.

The pharmacological management of the depressive episode in the context of bipolar disorder constitutes a challenge for the clinician both in adult and child-adolescent population. The objective of this paper is to update and synthesize the available evidence regarding the pharmacological management of bipolar depression in the pediatric population. Methodology: A search of the publications of the last 5 years in databases was carried out. Results: The evidence shows the use of second generation antipsychotics over mood stabilizers as the first line in this age group; demonstrating similar efficacy. Results: The evidence shows the use of second generation antipsychotics over mood stabilizers as the first line in this age group; demonstrating similar efficacy lurasidone and lanzapine/fluoxetine. Lurasidone is an option with a better safety profile as it is associated with fewer adverse effects and better adherence. The use of antidepressants should be considered within the initial steps of management, associated with a second generation antipsychotic. Conclusions: The importance of suspicion, evaluation and adequate diagnosis to guide the decision of comprehensive management is highlighted. Despite the existing risks and considerations, it is important to consider the first-line use of second-generation antipsychotics and antidepressants in the management of a depressive episode in the context of bipolar illness. The scarcity of studies on the pharmacological treatment of bipolar depression in general and especially in the pediatric population limits the generalization and extrapolation of the results to the local reality.

Para qué indicaciones se están utilizando los antidepresivos en adultos de Colombia / For What Indications are Antidepressants Being Used in Adults in Colombia?

RESUMEN Introducción: Los antidepresivos son útiles en el tratamiento farmacológico de diferentes trastornos depresivos y de ansiedad, además de su potencial utilidad para otras indicaciones. El objetivo del estudio es determinar las indicaciones para las que se están prescribiendo los antidepresivos a pacientes mayores de 18 años afiliados al Sistema de Salud de Colombia. Métodos: Estudio retrospectivo con datos de pacientes mayores de 18 años, de cualquier sexo, afiliados al Sistema de Salud de Colombia, a los que se prescriben antidepresivos; se revisaron las historias clínicas buscando indicaciones aprobadas y no aprobadas por agencias reguladoras. Se identificó a los pacientes aleatoriamente, así como las variables sociodemográficas, clínicas y farmacológicas que se pudieran asociar con prescripciones para indicaciones no aprobadas. Resultados: Se evaluó a 351 pacientes, con una media de edad de 60,4 ± 15,3 años; el 72,6% eran mujeres; se atendieron en 34 ciudades, y los prescriptores principalmente fueron médico general (n = 276; 78,6%) y psiquiatra (n = 42; 12,0%). Los inhibidores selectivos de la recaptación de serotonina fueron los antidepresivos más prescritos (n = 204; 58,1%), seguidos de los atípicos (n = 76; 21,7%). Las indicaciones más frecuentes fueron depresión (n = 169; 48,1%), ansiedad (n = 48; 13,7%), dolor (n = 22; 6,3%) y trastornos del sueño (n = 17; 4,8%). Un total de 188 prescripciones (53,6%) se hicieron para indicaciones aprobadas y las 163 (46,4%) restantes se catalogaron como no aprobadas. Conclusiones: Los antidepresivos se están prescribiendo para tratar depresión, ansiedad, analgesia y trastornos del sueño, especialmente a mujeres adultas mayores, pero casi la mitad de las formulaciones fueron para indicaciones no aprobadas.

ABSTRACT Introduction: Antidepressants are useful in the pharmacological treatment of different depressive and anxiety disorders, as well as being potentially useful in other indications. The aim of the study was to determine the indications for which antidepressants are being prescribed in patients over 18 years of age registered with the Colombian Health System. Methods: Retrospective study with data from patients over 18 years old, of either sex, registered with the Colombian Health System, who are prescribed antidepressants. Medical records were reviewed, looking for indications approved and not approved by regulatory agencies. Patients were identified randomly, as well as the sociodemographic, clinical and pharmacological variables that could be associated with prescriptions for unapproved indications. Results: 351 patients were evaluated, with a mean age of 60.4 ± 15.3 years, of whom 72.6% were women. They were attended in 34 cities, with prescriptions mainly by general practitioners (n = 276; 78.6%), and psychiatrists (n = 42; 12.0%). Selective serotonin reuptake inhibitors were the most widely prescribed antidepressants (n = 204; 58.1%), followed by atypicals (n = 76; 21.7%). The most frequent indications were for depression (n = 169; 48.1%), anxiety (n = 48; 13.7%), pain (n = 22; 6.3%) and sleep disorders (n = 17; 4.8%). A total of 188 prescriptions (53.6%) were made for approved indications, and the remaining 163 (46.4%) were classified as unapproved. Conclusions: Antidepressants are being prescribed for the treatment of depression, anxiety, pain and sleep disorders, especially in older adult women, but almost half of the formulations were for unapproved indications.

Vitamina D: entre el brillo del sol y la oscuridad de la depresión / Vitamin D: Between the Brightness of the sun and the Darkness of Depression

RESUMEN Introducción: La literatura científica indica que hay relación entre la vitamina D (VitD) y el inicio, el tratamiento y el pronóstico de la depresión. Sin embargo, esta línea de investigación continúa siendo motivo de controversia. El propósito del trabajo es analizar la relación entre la depresión y los valores de VitD, controlando por la influencia de la estación. Material y métodos: Estudio observacional y transversal. La muestra quedó conformada por 150 voluntarias adultas (edad, 28-78 arios). Se estratificó la muestra en 3 grupos: depresión sin tratamiento, depresión en tratamiento con antidepresivos y sin depresión (control). Se compararon los valores de VitD. Resultados: Se hallaron diferencias significativas entre los 3 grupos de comparación. El grupo con depresión sin tratamiento obtuvo los valores de VitD más bajos (media, 18,62 ± 8,42 ng/ml), compatibles con una insuficiencia grave. El grupo de participantes con depresión en tratamiento obtuvo valores más altos que el grupo anterior, aunque en la franja de insufi ciencia (23,80 ± 11,30 ng/ml). El tercer grupo (control) obtuvo los valores más altos y acordes con el intervalo deseable (30,19 ± 10,21 ng/ml). No hubo diferencias de edad entre los grupos. Al controlar por posibles efectos de la estación del año, las diferencias previas de VitD entre los 3 grupos se mantuvieron, con un descenso ostensible de todas las medias en el periodo invernal. Conclusiones: La depresión se asocia con valores de VitD insuficientes. El tratamiento con antidepresivos mejora esos valores, aunque continúan siendo insuficientes. Los hallazgos de este estudio refuerzan la evidencia de una asociación entre la depresión y la VitD.

ABSTRACT Introduction: The scientific literature suggests a relationship between vitamin D (VitD) and the onset, treatment and prognosis of depression. However, this line of research continues to be controversial. The aim of the study was to analyse the relationship between depression and VitD values, controlling for the influence of the season. Material and methods: Observational and cross-sectional study. The sample was made up of 150 adult female volunteer participants (aged between 28 and 78 years). The sample was stratified into three groups: a) depression without treatment, b) depression under treat ment with antidepressants, and c) without depression (control). VitD values (ng/ml) were compared. Results: Significant differences were found between the three groups surveyed. The group of participants with depression without treatment obtained the lowest VitD values (mean 18.62 ng/ml; SD 8.42), compatible with severe insufficiency. The group of participants with depression in treatment obtained higher values than the previous group, although in an insufficient range (mean 23.80 ng/ml; SD 11.30). The third group (control) obtained the hig hest values and in accordance with the desirable range (mean 30.19 ng/ml; SD 10.21). There were no age differences between the groups. When controlling for possible effects of the season, the previous differences in VitD between the three groups were maintained, with an evident decrease of all the mean levels in the winter period. Conclusions: Depression is associated with insufficient VitD values. Treatment with antidepressants improves these values, although they continue to be insufficient. The findings of this study reinforce the evidence for an association between depression and VitD.

Eficacia y seguridad de antipsicóticos y antidepresivos en el tratamiento de la anorexia nerviosa: revisión sistemática / Efficacy and Safety of Antipsychotics and Antidepressants in the Treatment of Anorexia Nervosa: a Systematic Review

RESUMEN Introducción: Las recomendaciones de las guías vigentes están basadas en evidencia de baja calidad. Se requiere su actualización periódica considerando la evidencia reciente. Objetivo: Sintetizar la mejor evidencia clínica disponible sobre eficacia y seguridad de antidepresivos y antipsicóticos de segunda generación en pacientes con anorexia nerviosa. Métodos: Revisión sistemática (CRD42020150577). Se buscaron en PubMed, SCOPUS, Ovid(Cochrane), EMBASE y LILACS los ensayos clínicos aleatorizados realizados en pacientes con anorexia nerviosa que evaluasen el uso de antipsicóticos de segunda generación o antidepresivos orales a cualquier dosis y por cualquier tiempo en el tratamiento ambulatorio y/u hospitalario tomando como resultados el peso (índice de masa corporal), las entidades psicopatológicas y la seguridad. Resultados: Se incluyeron 5 estudios, 4 catalogados como con alto riesgo de sesgo. La evidencia indica que los pacientes que reciben tratamiento con olanzapina o fluoxetina tienden a mantenerse por más tiempo dentro de los programas de tratamiento. La olanzapina mostró resultados favorables (un estudio) en cuanto al aumento de peso, pero no mostró los mismos resultados en psicopatología, donde la evidencia es contradictoria. Conclusiones: En concordancia con las revisiones anteriores, nuestro trabajo permite concluir que hay información contradictoria sobre la eficacia de los psicofármacos para la anorexia nerviosa. El trabajo futuro debe enfocarse en desarrollar ensayos clínicos de alta calidad metodológica.

ABSTRACT Introduction: The recommendations of the current guidelines are based on low quality evidence. Periodic updating is required, taking recent evidence into consideration. Objective: To synthesise the best available clinical evidence on the efficacy and safety of second-generation antidepressants and antipsychotics in patients with anorexia nervosa. Methods: Systematic review (CRD42020150577). We searched PubMed, SCOPUS, Ovid(Cochrane), EMBASE and LILACS for randomised clinical trials performed in patients with anorexia nervosa that evaluated the use of second-generation antipsychotics or oral antidepressants, at any dose and for any length of time, in outpatient and/or hospital treatment, taking weight (body mass index), psychopathological entities and safety as results. Results: Five studies were included, with four assessed as having a high risk of bias. The evidence indicates that patients receiving treatment with olanzapine or fluoxetine tend to stay in treatment programmes for longer. Olanzapine showed favourable results (one study) in terms of weight gain, but did not show the same results in psychopathology, where the evidence is contradictory. Conclusions: In accordance with previous reviews, our work allows us to conclude that there is contradictory information on the efficacy of psychotropic drugs in the treatment of anorexia nervosa. Future work should focus on developing clinical trials of high methodological quality.

Total serum cholesterol level in patients with major depressive disorder: Simple yet undermined

Human brain cholesterol acts as structural components of cellular membrane, synapse and dendrite formation.Researchers have found a possible association between low serum cholesterol levels and mood disorders though the literature from India in this regard is limited. To estimate serum levels of total cholesterol in patients with major depressive disorder. 75 patients of MDD were compared with equal number of age and sex matched controls. 5 ml of fasting sample of blood was obtained in a plain vacutainer to analyse total cholesterol level by Cholesterol oxidase-peroxidase method. Statistical analysis: The obtained results were tabulated and analyzed by multiple logistic regression analysis, independent t-test, Chi-square test and area under the curve. The mean level of cholesterol in cases (158.85±61.22 mg/dL) which was significantly lower compared to the controls (182.71±40.98 mg/dL) with P <0.01. The symptoms of MDD negatively correlated with lower serum cholesterol level with odds ratio of 0.99. There was statistically significant lower level of cholesterol in the MDD group below 140 mg/dL compared to the control group with P <0.001. As the measurement of total serum cholesterol is simple and cost effective, it can be used as an important biochemical marker for MDD.

Effect of Mentone® on depression- and anxiety-like profiles and regional brain neurochemistry in the adolescent Wistar Kyoto rat, a putative model of endogenous depression

Objectives: Antidepressants, when prescribed to treat adolescent depression tend to induce adverse effects, including suicidal tendencies. This is because the adolescent brain circuitry is still maturing and is therefore extremely vulnerable. As such, the search is on for compounds for use in complementary/alternative medicine. Polyherbal formulations are widely used as therapeutic alternatives for the treatment of depression. Such formulations and plant extracts are being studied in adult rodent models using standard pharmacological parameters, but not much emphasis has been given to testing the same in adolescents and endogenous animal models of depression. Therefore, the present study was focused on testing out the effect of the polyherbal formulation Mentone® on depression- and anxiety-like profiles and brain neurochemistry in the adolescent Wistar Kyoto rat (WKY), a putative model of endogenous and treatment-resistant depression (TRD). Materials and Methods: Mentone®, a polyherbal formulation comprising of four different plant species: Centella asiatica (Brahmi), Evolvulus alsinoides (Shankapushpi), Tinospora cordifolia (Guduchi), and Glycyrrhiza glabra (Yashtimadhu) was tested at two (18 and 36 mg/kg body weight) doses from the post-natal day (pnd) 25 to pnd 42 using standard neurobehavioral paradigms. Vehicular controls were intubated with saline and positive controls with 10 mg/kg body weight of conventional antidepressant, Fluoxetine. From pnd 35 onwards, animals were tested on a battery of tests, including sucrose preference, novel open field, elevated plus maze, and forced swim or Porsolt’s learned helplessness test. On pnd 42, animals were sacrificed and brain regional tissues such as the Prefrontal cortex (PFC), Striatum (Str), Nucleus Accumbens (NAc), and Hippocampus were microdissected out and subjected to reverse phase HPLC for the separation and quantification of monoamines: Norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites, 3,4-Dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in reference to external standards. Results: Mentone® reversed anhedonia by increasing sucrose consumption in Mentone®-treated as compared to Fluoxetine-treated groups. However, there was no effect on anxiety-related parameters in the novel open field or elevated plus-maze. Mentone® exhibited significant anti-depressant-like effects as indicated by its ability to reduce swim stress-induced immobility in Porsolt’s behavioural despair test with a concomitant increase in climbing or struggling behaviour, signifying reversal of depressive-like symptomatology. HPLC-based separation and quantification of brain regional levels of monoamines and their metabolites revealed increased DA levels in NAc and Str in treated groups with decreased levels of metabolite DOPAC in Mentone®-treated groups indicating increased DA tone. Significantly reduced 5-HT metabolite 5-HIAA levels in both PFC and Str is indicative of increased 5-HT tone in both Mentone®- and Fluoxetine-treated groups. NE was variably affected. Conclusion: While no anxiolytic effects and differential neurochemical effects were observed in brain regional areas in relation to Mentone® and Fluoxetine treatment, anhedonia and forced swim test, which are gold-standard tests for assessing depressive-like profiles indicated an effect of Mentone® that was on par with Fluoxetine. Thus, studies on such Ayurvedic formulations would enable a teasing out or differentiation between anxiolytic-like and depressive-like symptomatology and could constitute a source that holds promise in the development of complementary/alternative therapies for the treatment of depression in general and TRD in particular.

Evaluation of antidepressant activity of ondansetron in rodent models of depression

Background: At present, there is an escalating concern regarding possible role of 5-HT3 receptor in psychopharmacology and the therapeutic potential of their antagonists. Moreover, inclusion of 5-HT3 receptor antagonist may curtail the antidepressant-induced LTP decrease causing memory deficits, thereby improving efficacy of current antidepressants. Aim and Objective: This study aims to evaluate the antidepressant activity of 5-HT3 antagonist, that is, ondansetron (OND) in rodent models of depression. Materials and Methods: Male Swiss albino mice (20–30 g bw) and Wistar rats (100–200 g bw) were divided into five groups. Animals received either OND p.o. (0.1, 0.5 and 1 mg/kg), venlafaxine (10 mg/kg), or vehicle (1 ml distilled water p.o.) in control. Tail suspension and forced swim test were used to evaluate the effects of drugs and control after 60 min of their administration. Furthermore, assessment of locomotor activity (LA) was done by photoactometer after 24 h of drug administration. Results: Ondansetron exhibited significant antidepressants activity (P < 0.05) in rodent models. However, LA was not significantly altered by OND. Conclusion: Ondansetron exhibited significant antidepressant activity in rodent models hence paving the way for exploration of 5-HT3 receptor antagonist in future researches and its therapeutic application in depression.

Perfil clínico e psiquiátrico de gestantes atendidas em uma unidade de saúde de Criciúma, Santa Catarina / Clinical and psychiatric profile of pregnant women treated at a health unit in Criciúma, Santa Catarina, Brazil

Introdução: A gestação é um período transacional, que faz parte do curso natural do desenvolvimento humano e da renovação geracional. Esse período representa, para a mulher, o enfrentamento de desafios diversos e pode desencadear ou exacerbar transtornos psiquiátricos, podendo ser considerada a fase de maior incidência de alterações psíquicas na mulher. Assim, o objetivo do presente estudo é conhecer o perfil clínico e psiquiátrico de gestantes atendidas em uma unidade de saúde municipal do sul catarinense. Métodos: O presente estudo é do tipo observacional, retrospectivo, transversal, descritivo, com coleta de dados secundários e abordagem quantitativa, com registros que constam em prontuários de gestantes ali atendidas. Resultados: Foram avaliadas 179 gestantes com média de idade de 25,94 (± 6,43) anos e média de IMC pré-gestacional de 27,12 (± 6,01) kg/m² (sobrepeso), casadas (42,9%), escolaridade até o ensino médio (50,5%) e que possuíam alguma comorbidade clínica, principalmente hipertensiva (34,4%) ou diabetes mellitus (34,4%), exceto gestantes de baixo peso, nas quais há maior prevalência de asma. Sobre os transtornos psiquiátricos presentes, eram majoritariamente ansiosos e depressivos, sendo a fluoxetina o psicofármaco predominante. Conclusão: O perfil clínico e psiquiátrico de gestantes do presente estudo é de mulheres jovens, casadas, com sobrepeso, hipertensas ou diabéticas, que estudaram até o ensino médio, já possuem gestação prévia e não desejam a gestação atual. Entre as que possuem transtorno psiquiátrico, a maioria sofre de transtorno depressivo ou ansioso e são tratadas com ISRS. São sugeridos estudos para avaliar o desfecho do binômio mãe-feto e maior atenção à psicoterapia cognitivo-comportamental.

Introduction: Pregnancy, a transactional period, is part of the natural course of human development and generational renewal. This period represents different challenges for women and can trigger or exacerbate psychiatric disorders. It can be considered the phase with the highest incidence of psychiatric changes in women. Thus, this study's objective was to determine the clinical and psychiatric profile of pregnant women treated at a municipal health unit in the southern region of Santa Catarina state. Methods: This cross-sectional, retrospective observational descriptive study involved secondary data and a quantitative approach, assessing medical records of pregnant women treated at the clinic. Results: A total of 179 pregnant women were included, whose mean age was 25.94 (SD, 6.43) years and mean pre-pregnancy BMI was 27.12 (SD, 6.01) kg/m² (ie, overweight). A total of 42.9 % were married and the education level of 50.5% was less than high school. Most had some clinical comorbidity, mainly hypertension (34.4%) or diabetes mellitus (34.4%); there was a higher prevalence of asthma among those with low weight. The psychiatric disorders were mostly anxiety and depression, with fluoxetine being the most prescribed psychotropic drug. Conclusion: The clinical and psychiatric profile of this sample of pregnant women was young, married, overweight, hypertensive or diabetic women, with a less than high school education, previous pregnancies, and an unwanted current pregnancy. Most suffered from depressexualsive or anxiety disorder and were being treated with selective serotonin reuptake inhibitors. Studies are needed to assess the outcome of the mother-fetus pair, focusing on cognitive-behavioral psychotherapy.

Avaliação do uso de psicofármacos por universitários / Evaluation of the use of psychopharmaceuticals by university students

Introdução: depressão e ansiedade têm sido observadas entre universitários, sendo apontado como desencadeadores a sobrecarga de tarefas, cobranças pessoais e familiares entre outros fatores que podem resultar na necessidade de uso de psicofármacos. Objetivo: avaliar o uso de psicofármacos por universitários. Metodologia: estudo transversal, utilizando questionário contendo informações sociodemográficas, econômicas e sobre uso de psicofármacos. Foi realizada análise bivariada com teste qui-quadrado de Pearson para verificar associação entre as variáveis utilização de antidepressivos/ansiolíticos e sociodemográficas e econômicas. Resultados: dos 408 entrevistados, 22,3% afirmaram fazer uso de ansiolíticos/antidepressivos, tendo iniciado após o ingresso na universidade e em uso diário. A maioria relata ter alterado a dosagem sem consultar o médico, asseguraram conhecimento sobre os efeitos adversos do medicamento, sabe que a remoção do medicamento deve ser feita de maneira gradual, mas afirmam ter interrompido o tratamento sem consultar o médico. Permaneceram associadas a utilização de psicofármacos, no modelo final, ser do sexo feminino (p=0,013), idade maior que 29 anos (p=0,009) e possuir plano de saúde (p=0,020). Conclusão: verificou-se a necessidade de alertar a comunidade acadêmica e gestão sobre a necessidade de acolhimento dos universitários em sofrimento mental e propor ações que visem orientar sobre o uso racional dos psicofármacos.

Introduction: depression and anxiety have been observed among university students, with task overload, personal and family demands being pointed out as triggers, among other factors that result in the use of psychotropic drugs. Objective: to evaluate the use of psychopharmaceuticals by university students. Methodology: cross-sectional study, using a questionnaire containing sociodemographic, economic and psychotropic drug use information. A bivariate analysis was performed with Pearson's chi-square test to verify the association between the variables use of antidepressants/anxiolytics and sociodemographic and economic variables. Results: of the 408 respondents, 22.3% said they used anxiolytics/antidepressants, having started after entering university and in daily use. The majority report having changed the dosage without consulting the doctor, assured knowledge about the adverse effects of the medication, know that the removal of the medication must be done gradually, but claim to have stopped the treatment without consulting the doctor. The use of psychotropic drugs in the final model, being female (p=0.013), older than 29 years (p=0.009) and having a health plan (p=0.020) remained associated. Conclusion: there was a need to alert the academic and management community about the need to welcome university students in mental distress and propose actions that aim to guide the rational use of psychotropic drugs.

Eficácia e segurança de Duloxetina comparado a outros antidepressivos disponíveis no SUS para o tratamento de depressão maior: revisão rápida de evidências / Effectiveness and safety of Duloxetine compared to other antidepressant agents available in Brazilian Public Health for treatment of major depression: rapid response review of evidence

Tecnologia: Duloxetina e outros antidepressivos disponíveis no Sistema Único de Saúde (amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona). Indicação: Tratamento do primeiro episódio depressivo no transtorno de depressão maior em adultos. Pergunta: A duloxetina é mais eficaz e tolerável que a amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona para o tratamento do primeiro episódio de depressão maior em adultos? 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 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada 1 revisão sistemática, que atendia aos critérios de inclusão. Conclusão: Os antidepressivos, comparados ao placebo, tinham maior taxa de resposta, taxa de remissão e taxa de descontinuação devido a efeitos colaterais, no tratamento de curto prazo. Duloxetina tinha taxa de resposta similar a amitriptilina, clomipramina, fluoxetina e bupropiona. Duloxetina e amitriptilina tinham maior taxa de remissão que fluoxetina. Comparando-se as taxas de abandono de tratamento devido a efeitos colaterais, clomipramina era menos seguro, amitriptilina, bupropiona e duloxetina eram parecidos entre si, e fluoxetina era o antidepressivo mais seguro

Technology: Duloxetine and other antidepressants available in the Brazilian Public Health System (amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion). Indication: Treatment of the first depressive episode in adult major depressive disorder. Question: Is duloxetine more effective and tolerable than amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion for the treatment of first episode of major depression in adults? Methods: Rapid response review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: One systematic review was selected, which met the inclusion criteria. Conclusion: In short-term treatment, antidepressants, compared to placebo, had a higher rate of response, rate of remission and rate drop-out due to side effects. Duloxetine had a similar response rate to amitriptyline, clomipramine, fluoxetine and bupropion. Duloxetine and amitriptyline had higher remission rates than fluoxetine. Comparing rates of dropout due to side effects, clomipramine had the worst rates, amitriptyline, bupropion, and duloxetine were similar to each other, and fluoxetine had the better rates

Late-life depression and the family physician

Late-life depression (LLD) is a common disorder seen in clinical practice. Depression in this population group is often left undetected and untreated. The majority of elderly individuals who seek help present to the primary health care setting. The family physician is ideally placed to screen for symptoms of LLD, given that they often have longitudinal knowledge of the patient's history, premorbid personality, functioning and overall health status. An understanding of risk factors, differential diagnoses, appropriate opportunistic screening toolsand decision-making around management plans can assist the family physician in the early detection and treatment of these patients. In doing so, this may lead to a decrease in mortality and morbidity and enhance the patient's quality of life.Keywords: Late life; depression; older; geriatric mental health; major depressive disorder; antidepressants; cognitive impairment; dementia.

Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Some depressed patients receive acupuncture as an adjunct to their conventional medications.@*OBJECTIVE@#This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.@*SEARCH STRATEGY@#English and Chinese databases were searched for randomized controlled trials (RCTs) published until December 1, 2021.@*INCLUSION CRITERIA@#RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.@*DATA EXTRACTION AND ANALYSIS@#Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran's Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence in the included studies.@*RESULTS@#This review included 16 studies (with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17 (HAMD-17) scores (standard mean difference [SMD] -0.44, 95% confidence interval [CI] -0.55 to -0.33, P < 0.01; I2 = 14%), Self-rating Depression Scale (SDS) scores (SMD -0.53, 95% CI -0.84 to -0.23, P < 0.01; I2 = 79%), and the Side Effect Rating Scale (SERS) scores (SMD -1.11, 95% CI -1.56 to -0.66, P < 0.01; I2 = 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores (SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01; I2 = 15%), decreased the number of participants who increased their antidepressant dosages (relative risk [RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01; I2 = 0%), and resulted in significantly higher remission rates (RR 1.52, 95% CI 1.26 to 1.83, P < 0.01; I2 = 0%) and treatment responses (RR 1.35, 95% CI 1.24 to 1.47, P < 0.01; I2 = 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.@*CONCLUSION@#Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.@*SYSTEMATIC REVIEW REGISTRATION@#INPLASY202150008.

Use of benzodiazepines and antidepressants in patients who attend a Rheumatology clinic / Prevalencia de consumo de benzodiacepinas y antidepresivos en los pacientes que acuden por primera vez a la consulta de reumatología

ABSTRACT Introduction: During the last decades, benzodiazepines (BZD) and antidepressants (ADP) have been among the most prescribed therapies in all developed countries. They have side effects, and BZD carry a risk of abuse and dependence disorders. The purpose of this study was to evaluate the prevalence of BZD and ADP among patients who attend a Rheumatology clinic, as well as the indication for these drugs. Methods: The study included patients who were referred for the first time to the Rheumatology clinic. Demographical data, reason for referral, and final diagnosis were recorded. The indication for ADP and/or BZD was recorded, as well as the duration of treatment. Sample size was estimated for a 0.05% alpha risk. Univariate and multivariate analyses were performed in order to study the relationships with the demographical or clinical characteristics. Results: A total of 350 patients were included (women 77.1%, men 22.9%). Most of them (73.4%) had been referred for musculoskeletal pain. More than a third (36.6%) of patients were on BZD and/or ADP. The most frequent reasons for their prescription were anxiety, depression, and insomnia. The final diagnosis in the clinic was a non-inflammatory condition in 82%, and an inflammatory one in 18%. In the univariate analyses, the use of BZD/ADP was associated with female gender (p<.001), unemployment (p<.001) and non-inflammatory final diagnosis (p < .001). In the multivariate analyses, the use of BZD and/or ADP was associated with female sex (p = .002 [OR 3.4, 95% CI; 1.6-7.4]), and a non-inflammatory final diagnosis, specifically fibromyalgia (p = .007 [OR 16.1, 95% CI; 2.2-120.7]). Conclusion: Use of BZD and ADP is high and associated with non-inflammatory disease.

RESUMEN Introducción: Durante las últimas décadas, las benzodiacepinas (BZD) y los antidepresivos (ADP) han estado entre las terapias más prescritas en todos los países desarrollados. Estos fármacos tienen efectos secundarios y las BZD pueden ocasionar abuso y problemas de dependencia. El objetivo de este estudio fue evaluar la prevalencia de consumo de BZD y ADP entre los pacientes que acuden a una consulta de reumatología por primera vez, así como la indicación para ellos. Métodos: Se incluyeron pacientes remitidos por primera vez a la consulta de reumatología. Se registraron los datos demográficos, el motivo de la derivación y el diagnóstico final. Con respecto al tratamiento con ADP y/o BZD, se registraron su duración y la indicación de la prescripción. El tamaño de la muestra se estimó para un riesgo alfa de 0,05%. Se realizaron análisis univariantes y multivariantes para estudiar las asociaciones con características demográficas o clínicas. Resultados: Se incluyeron 350 pacientes (mujeres 77,1%, hombres 22,9%). La mayoría de ellos habían sido remitidos por dolor musculoesquelético (73,4%). Más de un tercio (36,6%) de los pacientes estaban en tratamiento con BZD y/o ADP. Las causas más frecuentes para su prescripción fueron ansiedad, depresión e insomnio. El diagnóstico final fue patología no inflamatoria en el 82% de los casos e inflamatoria en el 18% de estos. En el análisis univariante, el uso de BZD y/o ADP se asoció con el sexo femenino (p< 0,001), el desempleo (p< 0,001) y el diagnóstico de patología no inflamatoria (p< 0,001). En el análisis multivariante, el uso de BZD y/o ADP se asoció con el sexo femenino (p=0,002 [OR 3,4; IC 95% 1,6-7,4]) y el diagnóstico de patología no inflamatoria, específicamente con la fibromyalgia (p = 0,007 [OR 16,1; IC 95% 2,2-120,7]). Conclusión: El consumo de BZD y ADP es frecuente y está asociado con patología no inflamatoria.