La relación entre la transición a la menopausia y los trastornos del estado de ánimo / The relationship between menopause transition and mood disorders

Este estudio tuvo como objetivo examinar la relación entre la transición a la menopausia y los trastornos del estado de ánimo, específicamente la ansiedad y la depresión. Se llevó a cabo una revisión narrativa de la literatura relevante sobre la transición a la menopausia y los trastornos del estado de ánimo. Se revisaron estudios que se enfocaron en el impacto de los cambios hormonales durante la menopausia en el bienestar psicológico y se evaluaron diversas opciones de tratamiento para los trastornos del estado de ánimo. La disminución de los niveles hormonales de estrógenos y progesterona durante la menopausia puede llevar a diversos cambios psicológicos, como ansiedad y depresión. La terapia hormonal con estrógenos solo o en combinación con progesterona puede mejorar los síntomas depresivos en mujeres en la menopausia, pero este tratamiento no está exento de riesgos. Otros tratamientos no hormonales, como la terapia cognitivo-conductual, el ejercicio y una buena higiene del sueño, también pueden ser efectivos para manejar los trastornos del estado de ánimo. Se concluyó que existe una compleja interacción entre factores hormonales, biológicos y psicosociales para desarrollar intervenciones efectivas que mejoren el bienestar psicológico de las mujeres en la menopausia.

This study aimed to examine the relationship between menopause transition and mood disorders, specifically anxiety and depression. The authors conducted a narrative review of relevant literature on menopause transition and mood disorders. They reviewed studies that focused on the impact of hormonal changes during menopause on psychological well-being and evaluated various treatment options for mood disorders. The decline in estrogen and progesterone hormone levels during menopause can lead to various psychological changes, such as anxiety and depression. Hormonal therapy with estrogen alone or in combination with progesterone can improve depressive symptoms in menopausal women, but this treatment is not without risks. Other non-hormonal treatments, such as cognitive-behavioral therapy, exercise, and good sleep hygiene, can also be effective in managing mood disorders. The study highlights the need for recognition of the complex interplay between hormonal, biological, and psychosocial factors in developing effective interventions to improve the psychological well-being of menopausal women. Further research is needed to fully understand the potential relationship between menopause transition and mood disorders.

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)

Intoxicaciones por benzodiacepinas y antidepresivos, una realidad preocupante / Epidemiological Characterization of Benzodiazepine and Antidepressant Poisonings in Chile

INTRODUCTION: Poisonings are a worldwide preventable public health problem that affects the general population. OBJECTIVE: To epidemiologically characterize BZ and AD poisonings registered in Chile between 2002 and 2019. METHODS: An observational retrospective study of poisonings registered in the medical outcome report system of the Chilean Ministry of Health was conducted. The World Health Organization International Classification of Disease codes T42.2, T43.0 and T43.2 were included. RESULTS: 22,807 poisonings associated with BZ or AD were identified, representing 0.08% of all hospitalizations. Poisoning rates distribution were established at regional and national level. There were 9.8% of accidental events, 63.7% of intentional events, and 26.5% of undetermined cases. The highest accidental and intentional poisoning rates were estimated at the ages of 0 to 4 and 15 to 19 years old respectively. Poisoned patients remained hospitalized on average for 3.4 days. 0.3% of cases were related to death of patients. CONCLUSIONS: Poisoning events were characterized according to the studied variables. National poisoning rates decreased over the years with prevalence of those intentional events linked to women. Efforts should be made in creating poisoning prevention campaigns focused on age-based groups in the general population.

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

Research progress on the correlation between transforming growth factor- β level and symptoms of depression / 浙江大学学报·医学版

Transforming growth factor (TGF)-β is a group of cytokines with anti-inflammatory effects in the TGF family, which participates in the development of stress and depression-related mechanisms, and plays roles in the regulation of inflammatory response in depression and the recovery of various cytokine imbalances. The core symptoms of depression is associated with TGF-β level, and the psychological symptoms of depression are related to TGF-β gene polymorphism. Various antidepressants may up-regulate TGF-β level through the complex interaction between neurotransmitters and inflammatory factors, inhibiting inflammatory response and regulating cytokine imbalance to improve depressive symptoms. Studies have shown that recombinant TGF-β1 protein has beneficial effects in mouse depression models, indicating TGF-β1 might be a potential therapeutic target for depression and nasal sprays having the advantage of being fast acting delivery method. This article reviews the research progress on dynamic changes of TGF-β level before and after depression treatment and the application of TGF-β level as an indicator for the improvement of depressive symptoms. We provide ideas for the development of new antidepressants and for the evaluation of the treatment efficacy in depression.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges / 神经科学通报·英文版

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

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

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

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Comparison of mouse models of depression induced by different modeling methods / 生理学报

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.

Antidepressant mechanism of Shenling Kaixin Granules based on BDNF/TrkB/CREB pathway / 中国中药杂志

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

Research progress in pharmacotherapy of insomnia / 中国中药杂志

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.

Gender differences in antidepressant effect of raw Rehmanniae Radix / 中国中药杂志

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Anxiolytic and antidepressant effects of agarwood inhalation and its mechanism / 中国中药杂志

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.

Sentimentos e percepções do luto de sobreviventes ao suicídio de jovens / Feelings and perceptions of grief among survivors of youth suicide / Sentimientos y percepciones de duelo entre sobrevivientes de suicidio de jóvenes

Sobreviventes ao suicídio são pessoas que têm suas vidas profundamente afetadas e apresentam sofrimento psicológico, físico ou social após serem expostas a esse fato. O objetivo deste estudo foi analisar a experiência de sobreviventes ao suicídio de jovens, a partir do luto. Participaram sete sobreviventes entre familiares, amigos e parceiros amorosos de jovens que cometeram suicídio. A análise de conteúdo de entrevistas narrativas apontou que os participantes utilizam explicações racionalizadas ou dissociadas, criando uma distância entre o evento e eles mesmos. Como formas de lidar com o sofrimento podem buscar o isolamento, apoio entre amigos, prática religiosa e/ou a dedicação ao trabalho. Reafirma-se a dimensão do luto diante dessa experiência, além da importância da prevenção ao suicídio e da posvenção aos sobreviventes.(AU)

Suicide survivors are people who have their lives deeply affected; they experience psychological, physical, and social suffering following the occurrence. The aim of this study is to analyze the experience of survivors of youth suicide attempts, based on grief. Seven survivors participated among family, friends, and romantic partners of young people who committed suicide. The content analysis of narrative interviews showed that the participants use rationalized or dissociated explanations, creating a distance between the event and themselves. As ways to deal with suffering, they seek isolation, support among friends, religious practice, and/or dedication to work. The dimension of grief in the face of this experience is reaffirmed, as well as the importance of suicide prevention and postvention for survivors.(AU)

Este artículo tiene como objetivo presentar la construcción metodológica desarrollada en una investigación de maestría, en la que sostenemos la escritura de escenas como método de investigación de la escucha clínica. Las escenas del trabajo en cuestión se recogieron a lo largo del tiempo desde la experiencia en un proyecto de extensión universitario de atención a la niñez y adolescencia en situación de vulnerabilidad social aplicado en una comunidad periférica. En este texto, presentamos los interrogantes que se elaboraron en torno a la elección por el trabajo con escenas y compartimos el rescate histórico de las mismas como un método de escribir la clínica y la reanudación del análisis a partir de la tradición psicoanalítica. Amparadas en el psicoanálisis y en lecturas y contribuciones del filósofo francés Jacques Derrida, nos basaremos en la noción de que la escena se constituye como un lugar de producción, engendrando la configuración particular de elementos significantes en los procesos de subjetivación y de construcción social. La escena no es aquí una representación de lo que pasa en la clínica, sino un modo de producir escucha y sus procesos de investigación.(AU)

Saúde mental e cotas: um estudo comparativo entre estudantes universitários no Brasil / Mental health and quotas: a comparative study among university students in Brazil / Salud mental y cuotas: un estudio comparativo entre estudiantes universitarios en Brasil

Com a instauração da política de cotas, ocorreram profundas transformações no perfil dos estudantes das universidades públicas brasileiras. Essa nova composição do corpo discente, com maior representatividade de minorias e/ou estudantes de baixa renda, traz consigo novas demandas relacionadas à saúde mental do estudante. Apesar disso, ainda são escassas as pesquisas que investiguem esse contexto específico. Este estudo visa comparar a saúde mental de estudantes cotistas e não cotistas, avaliando diferenças nas prevalências de sintomas de depressão, ansiedade e estresse entre os dois grupos. Participaram da pesquisa 6.103 estudantes de graduação de uma universidade pública federal, dos quais 2.983 (48,88%) cotistas e 3.120 (51,12%) não cotistas. O levantamento de dados foi feito por meio de questionário on-line contendo questionário sociodemográfico e de hábitos de vida, e pelo Depression Anxiety and Stress Scale, na sua versão reduzida de 21 itens (DASS-21), utilizada para avaliar sintomas de depressão, ansiedade e estresse. Os resultados indicaram que os estudantes cotistas apresentaram maiores prevalências de sintomas de depressão e ansiedade quando comparados aos não cotistas. As áreas de Ciências Exatas e da Terra, e os Bacharelados Interdisciplinares apresentaram maiores diferenças entre os dois grupos em relação a esses problemas em saúde mental. Os resultados apontam para a necessidade de que as universidades estejam atentas às novas demandas em saúde mental dos estudantes e que estas sejam contempladas nas políticas de atenção à saúde estudantil.(AU)

With the introduction of the quota policy, profound changes took place in the profile of students in Brazilian public universities. This new composition of the student body, with greater representation of minorities and/or low-income students, brings new demands related to student mental health. Despite this, there are still few studies investigating this specific context. This study aims to compare the mental health of quota and non-quota students, evaluating differences in the prevalence of symptoms of depression, anxiety, and stress between the two groups. A total of 6,103 undergraduate students from a federal public university participated in the research, of which 2,983 (48.88%) were quota students and 3,120 (51.12%) were nonquota students. Data collection was carried out via an online questionnaire containing a sociodemographic and lifestyle questionnaire, and the Depression Anxiety and Stress Scale, in its reduced version of 21 items (DASS-21) was used to assess symptoms of depression, anxiety, and stress. The results indicated that quota students had higher prevalence of symptoms of depression and anxiety when compared to non-quota students. The areas of Exact and Earth Sciences and Interdisciplinary Bachelors were the ones that showed the greatest differences between the two groups in relation to these mental health problems. The results point to the need for universities to be attentive to the new demands in mental health of students and for these to be included in student health care policies.(AU)

Con la introducción de la política de cuotas, se produjeron cambios profundos en el perfil de los estudiantes de las universidades públicas brasileñas. Esta nueva composición del alumnado, con mayor representación de minorías y/o estudiantes de escasos recursos, trae consigo nuevas demandas relacionadas con la salud mental del alumno. Pero todavía existen pocas investigaciones sobre el contexto específico. Este estudio tiene como objetivo comparar la salud mental de los estudiantes beneficiarios de las políticas de cuotas y los no beneficiarios, y evaluar las diferencias en la prevalencia de síntomas de depresión, ansiedad y estrés entre los dos grupos. En la investigación participaron un total de 6.103 estudiantes de grado de una universidad pública federal, de los cuales 2.983 (48,88%) son estudiantes beneficiarios y 3.120 (51,12%) son estudiantes no beneficiarios. Los datos se recolectaron de un formulario en línea, que estaba compuesto por un cuestionario sociodemográfico y de hábitos de vida, y por la Escala de Depresión, Ansiedad y Estrés, en su versión reducida de 21 ítems (DASS-21), utilizada para evaluar síntomas de depresión, ansiedad y estrés. Los resultados destacaron que los estudiantes beneficiarios de las políticas de cuotas tenían una mayor prevalencia de síntomas de depresión y ansiedad en comparación con los estudiantes no beneficiarios. Las áreas de Ciencias Exactas y de la Tierra y Licenciaturas Interdisciplinarias presentaron las mayores diferencias entre los dos grupos con relación a estos problemas en salud mental. Los resultados apuntan a la necesidad de que las universidades sean conscientes de las nuevas demandas sobre la salud mental de los estudiantes y de que estas se incluyan en las políticas de atención de la salud estudiantil.(AU)

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).

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

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

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

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

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

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

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

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