Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 124
Rev. Hosp. Ital. B. Aires (2004) ; 43(3): 116-120, sept. 2023. ilus, tab
Article in Spanish | BINACIS, LILACS, UNISALUD | ID: biblio-1517444


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)

Humans , Male , Female , Adult , Selective Serotonin Reuptake Inhibitors/administration & dosage , Depression/drug therapy , Education, Medical , Medical Staff, Hospital/education , Antidepressive Agents/administration & dosage , Reaction Time/drug effects , Cross-Sectional Studies , Surveys and Questionnaires , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Age and Sex Distribution , Antidepressive Agents/adverse effects , Antidepressive Agents/pharmacology
China Journal of Chinese Materia Medica ; (24): 5326-5336, 2023.
Article in Chinese | WPRIM | ID: wpr-1008730


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.

Male , Female , Mice , Animals , Yin Deficiency , NLR Family, Pyrin Domain-Containing 3 Protein , Sex Factors , Cyclooxygenase 2 , NF-kappa B , Antidepressive Agents/pharmacology
China Journal of Chinese Materia Medica ; (24): 5122-5130, 2023.
Article in Chinese | WPRIM | ID: wpr-1008710


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.

Humans , Sleep Initiation and Maintenance Disorders/chemically induced , Quality of Life , Sleep , Hypnotics and Sedatives/pharmacology , Antidepressive Agents/pharmacology
Chinese journal of integrative medicine ; (12): 405-412, 2023.
Article in English | WPRIM | ID: wpr-982291


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.

Male , Animals , Mice , Corticosterone , Fluoxetine/metabolism , Depression/chemically induced , Glycogen Synthase Kinase 3 beta/metabolism , Reproducibility of Results , Antidepressive Agents/pharmacology , Hippocampus , TOR Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , Behavior, Animal , Disease Models, Animal , Mammals/metabolism
China Journal of Chinese Materia Medica ; (24): 2184-2192, 2023.
Article in Chinese | WPRIM | ID: wpr-981349


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.

Rats , Male , Animals , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , Nerve Growth Factor/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Serotonin/metabolism , NF-E2-Related Factor 2/metabolism , Rats, Sprague-Dawley , Antidepressive Agents/pharmacology , Hippocampus/metabolism , Superoxide Dismutase/metabolism , Sugars/pharmacology , Depression/genetics , Stress, Psychological/metabolism
Acta Physiologica Sinica ; (6): 379-389, 2023.
Article in Chinese | WPRIM | ID: wpr-981014


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.

Mice , Animals , Depression/etiology , Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor , Serotonin
Acta Physiologica Sinica ; (6): 165-176, 2022.
Article in Chinese | WPRIM | ID: wpr-927592


This paper was aimed to clarify the effect of high-intensity interval training (HIIT) on depression. Animal running platforms were used to establish HIIT exercise models, depression models were prepared by chronic unpredictable mild stress (CUMS), and depression-related behaviors were detected by behavioral experiments. The results showed that HIIT exercise improved depression-related behavior in CUMS model mice. Western blot and ELISA results showed that in the hippocampus, medial prefrontal cortex (mPFC) and amygdala of the CUMS model mice, glucocorticoid receptor (GR) protein expression was down-regulated, and the content of tumor necrosis factor α (TNF-α) was increased, compared with those in the control group, whereas HIIT exercise could effectively reverse these changes in CUMS model mice. These results suggest that HIIT exercise can exert antidepressant effect, which brings new ideas and means for the clinical treatment of depressive diseases.

Animals , Mice , Antidepressive Agents/pharmacology , Behavior, Animal , Depression/drug therapy , Disease Models, Animal , Hippocampus/metabolism , Stress, Psychological/drug therapy
Rev. Ciênc. Plur ; 8(1): e25741, 2022. tab
Article in Portuguese | LILACS, BBO | ID: biblio-1348355


Introdução:Pacientes com depressão maior geralmente respondem ao tratamento com medicamentos antidepressivos, no entanto em 10% a 30% dos casos há apenas uma resposta parcial ou nenhuma resposta, entre os fatores que podem influenciar encontra-se o perfil das enzimas hepáticas metabolizadoras dos antidepressivos, tal como a CYP2C19.Objetivo:Caracterizar os indivíduos quanto ao perfil genético dospolimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e compará-los em relação a adesão ao tratamento, sintomas de depressão e qualidade de vida.Metodologia:Trata-se de um estudo transversal realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Após caracterização do perfil genético, os indivíduos foram comparados quanto aos dados demográfico e socioeconômico, adesão ao tratamento (TestedeMorisky-Green),sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF).Resultados:Quatro pacientes (13.8%) apresentaram polimorfismo para CYP2C19*2 e 10 pacientes (34.4%) para CYP2C19*17, com maior prevalência de CYP2C19*17 (p>0.05). Nenhuma associação significativa de características socioeconômicas, demográficas e clínicas entre os genótipos do CYP2C19.No TestedeMorisky-Green, aadesão moderada ao tratamento foi predominante nos pacientes CYP2C19*2 e CYP2C19*17 (p>0.05). Não foi observada associação entre sintomas de depressão e polimorfismos genéticos (p>0.05). Uma associação significativa entre o genótipo polimórfico CC do CYP2C19*17 com a satisfação com a saúde, enquanto o genótipo CT foi associado ao estado "nem satisfeito/nem insatisfeito" (p<0.05). A maioria dos indivíduos CYP2C19*2 e CYP2C19*17 relatou "necessidade de melhorar" em relação aos domínios de qualidade de vida físico, psicológico, social e ambiental (p>0.05).Conclusões:Os pacientes apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Alguns pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão moderado a intenso e relataram uma indefinição na satisfação da sua qualidade de vida (AU).

Introduction:Patients with major depression usually respond to treatment with antidepressant drugs, however in 10% to 30% of cases there is only a partial response or no response, among the factors that can influence is the profile of liver enzymes metabolizing antidepressants, such as CYP2C19.Objective:To characterize the individuals regarding the genetic profile ofCYP2C19*2or CYP2C19*17 polymorphisms in patients with major depressive disorder (MDD) treated with citalopram or escitalopram, and to compare themaccording to treatment adherence, symptoms of depression and quality of life.Methodology:This is cross-sectionalstudy carried out with 29 patients with MDD. Blood samples were collected for CYP2C19 genotyping by TaqMan® allelic discrimination. After characterization of the genetic profile, the individuals were compared regarding the demographic and socioeconomic data, treatment adherence (Morisky-GreenTest), symptoms of depression (Hamilton scale) and quality of life (WHOQoL-BREF).Results:Four patients showed (13.8%) CYP219*2 and 10 patients (34.4%) CYP219*17 polymorphisms.,withhigher prevalence of CYP219*17 (p>0.05). No association between socioeconomic, demographic, and clinical features with CYP2C19 genotypes was observed. In Morisky-GreenTest, moderate adherence to treatment was predominant for CYP2C19*2 and CYP219*17 patients (p>0.05). No statistically significant association was observed between symptoms of depression and genetic polymorphisms (p>0.05). A significant association between polymorphic CC genotype of CYP219*17 with health satisfaction, while the CT genotype was associated with "neither satisfied/nor dissatisfied" status (p<0.05). Most of the CYP2C19*2 and CYP2C19*17 subjects reported "need to improve" or "regular" regarding physical, psychological, social, and environmental domainsof quality of life(p>0.05).Conclusions:The patients showed a higher prevalence of CYP219*17 polymorphism, with moderate treatment adherence. Some subjects, even under the effect of the medication, presented moderate to intense symptoms of depression, and reported a lack of definition in the satisfaction of their quality of life (AU).

Introducción:Los pacientes con depresión mayor responder al tratamiento con antidepresivos, en 10% al 30% de los casos existe una respuesta parcial o nula, entre los factores que pueden influir se encuentra el perfil de enzimas hepáticas metabolizadoras de antidepresivos, como CYP2C19.Objetivo: Caracterizar a los individuos en cuanto al perfil genético depolimorfismos CYP2C19 *2 o CYP2C19 * 17 en pacientes con trastorno depresivo mayor (TDM) tratados con citalopram o escitalopram y compararlos en relaciónpara la adherencia al tratamiento, síntomas de depresión y la calidad de vida.Metodología: Estudio transversalcon 29 pacientes con TDM. Se recogieron muestras de sangre para la determinación del genotipo CYP2C19 mediante discriminación alélica TaqMan®, los individuos fueron comparados en cuanto a los datosdemográficosy socioeconómicos, adherencia (Prueba de Morisky-Green), síntomas de depresión (escala de Hamilton) y calidad de vida (WHOQoL-BREF).Resultados: Cuatro pacientes (13,8%) con polimorfismo CYP2C19*2 y 10 (34,4%) con CYP2C19 * 17,(p> 0,05). No existe una asociación significativa de las características socioeconómicas, demográficas y clínicas con los genotipos CYP2C19. La adherencia moderada al tratamiento fue predominante en los pacientes con CYP2C19*2 y CYP2C19*17 (p> 0,05). No hubo asociación entre síntomas de depresión y polimorfismos genéticos (p> 0.05). Una asociación significativa entre el genotipo polimórfico CYP2C19 * 17 CC con la satisfacción con la salud, mientras que el genotipo CT se asoció con el estado "ni satisfecho / no insatisfecho" (p <0.05). La mayoría de CYP2C19 * 2 y CYP2C19 * 17 individuos informaron "necesidad de mejorar" en relación con los dominios físico, psicológico, social y ambientalde calidad de vida(p> 0,05).Conclusiones: Los pacients mostraron una mayor prevalencia del CYP2C19 * 17, con adherencia moderada al tratamiento, síntomas de depresión moderada a intensay informaron una falta de definición en la satisfacción de su calidad de vida (AU).

Humans , Citalopram/pharmacology , Depression/drug therapy , Depressive Disorder, Major/drug therapy , Cytochrome P-450 CYP2C19/pharmacology , Antidepressive Agents/pharmacology , Quality of Life , Brazil , Cross-Sectional Studies/methods , Drug Therapy
Journal of Integrative Medicine ; (12): 442-452, 2022.
Article in English | WPRIM | ID: wpr-939906


OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Animals , Mice , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Adiponectin/metabolism , Antidepressive Agents/pharmacology , China , Depression/drug therapy , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Glucose , Hypothalamus/metabolism , Receptors, Adiponectin/metabolism
Braz. j. med. biol. res ; 54(2): e10107, 2021. graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1142578


Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.

Animals , Male , Rabbits , Brain/drug effects , Brain/enzymology , Brain-Derived Neurotrophic Factor/metabolism , Ketamine/pharmacology , Antidepressive Agents/pharmacology , Astrocytes , Glycogen Synthase Kinase 3 , Disease Models, Animal , Glial Fibrillary Acidic Protein , Histone Deacetylases
China Journal of Chinese Materia Medica ; (24): 3678-3686, 2021.
Article in Chinese | WPRIM | ID: wpr-888021


This study aimed to investigate the antidepressant effects of total alkaloids of Fibraurea recisa in HT22 cells damaged by corticosterone (CORT) in vitro and in a mouse model of chronic unpredictable mild stress (CUMS) as well as the underlying mechanisms.In cellular experiments,the viability of CORT-damaged HT22 cells was detected using cell counting kit-8 (CCK-8),and the cell apoptosis was detected by Hoechst 33258 staining.In animal experiments,C57BL/6N mice were randomly divided into the control group,model group,low (100 mg·kg~(-1)),medium (200 mg·kg~(-1)) and high (400 mg·kg~(-1))-dose of total alkaloids of F.recisa groups,and positive control group.After 21 days of CUMS exposure,their depressive behaviors were observed in behavioral and Morris water maze tests.The serum levels of 5-hydroxytryptamine (5-HT),dopamine (DA),and norepinephrine (NE) were assessed by ELISA.The expression levels of apoptosis-related proteins Bcl-2,Bax and cleaved caspase-3 in HT22 cells and mouse hippocampus were detected by Western blot.The results suggested that total alkaloids of F.recisa alleviated the damage of HT22 cells induced by CORT in a dose-dependent manner.The Hoechst 33258 staining uncovered that total alkaloids of F.recisa better reduced the blue spots and inhibited cell apoptosis.The results of animal experiments showed that total alkaloids of F.recisa significantly improved the depression-like behaviors of mice and increased the serum levels of 5-HT,DA and NE as compared with those in the model group.The Western blot assays revealed a significant up-regulation of Bcl-2 protein expression,but an obvious reduction in Bax and cleaved caspase-3protein expression in the total alkaloids of F.recisa group.In conclusion,total alkaloids of F.recisa inhibited depression possibly by regulating the apoptosis-related protein expression or elevating the monoamine neurotransmitter levels in the brain.

Animals , Mice , Alkaloids/pharmacology , Antidepressive Agents/pharmacology , Depression/drug therapy , Disease Models, Animal , Hippocampus , Mice, Inbred C57BL , Stress, Psychological
Rev. pediatr. electrón ; 17(3): 44-48, oct. 2020.
Article in Spanish | LILACS | ID: biblio-1367339


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

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

Humans , Female , Breast Feeding , Depression, Postpartum/drug therapy , Sertraline/therapeutic use , Antidepressive Agents/therapeutic use , Antidepressive Agents/pharmacology
Int. j. morphol ; 37(2): 576-583, June 2019. graf
Article in English | LILACS | ID: biblio-1002261


Antidepressants use during pregnancy was associated with an increased risk of autism spectrum disorders. Animal models based on early life alterations in serotonin availability replicate some of the anatomical and behavioral abnormalities observed in autistic individuals. In recent years there has been a growing interest in the possible role of the hippocampus in autism. The aim of study is to examine the effects of neonatal antidepressant (CTM) exposure during a sensitive period of brain development on pyramidal and granule cells density of hippocampal formation. We examined the pyramidal and granular cells density of dorsal hippocampus using Nissl stained sections obtained from neonatal citalopram (CTM) exposed rats (5 mg/kg, twice daily, s.c.), from postnatal day 8 to 21 (PN8-21), saline and non-exposed rats. The density of pyramidal cells was significantly increased by 10.2 % in CA1, 10.6 % in CA3 and 13.2 % in CA4 in CTM treated compared with non-treated or saline treated animals (p<0.0001). The density of granule cells in the dentate gyrus was significantly increased by 12.0 % in CTM treated compared with non-treated or saline treated animals (p<0.0001). These findings were obtained only from male rats, suggesting a sexual dimorphism in neural development after SSRI exposure. These data suggest that the neonatal exposure to CTM may induce long-lasting changes in the hippcampal formation in adults, and such effects appear to preferentially target males.

El uso de antidepresivos durante el embarazo se asoció con un mayor riesgo de trastornos del espectro autista. Los modelos animales basados en alteraciones tempranas de la vida en la disponibilidad de serotonina replican algunas de las anomalías anatómicas y de comportamiento observadas en individuos autistas. En los últimos años ha habido un interés creciente en el posible papel del hipocampo en el autismo. El objetivo del estudio fue examinar los efectos de la exposición al antidepresivo neonatal (CTM) durante un período sensible del desarrollo cerebral en la densidad de las células piramidales y granulares de la formación del hipocampo. Examinamos la densidad de las células piramidales y granulares del hipocampo dorsal utilizando secciones teñidas con Nissl obtenidas de ratas expuestas al citalopram neonatal (CTM) (5 mg / kg, dos veces al día, sc), desde el día postnatal 8 a 21 (PN8-21), solución salina y ratas no expuestas. La densidad de células piramidales se incrementó significativamente en un 10,2 % en CA1, 10,6 % en CA3 y 13,2 % en CA4 en CTM tratados en comparación con animales no tratados o tratados con solución salina (p <0,0001). La densidad de células granulares en el giro dentado aumentó significativamente en un 12,0 % en los animales tratados con CTM en comparación con los animales no tratados o tratados con solución salina (p <0,0001). Estos hallazgos se obtuvieron solo en ratas macho, lo que sugiere un dimorfismo sexual en el desarrollo neural después de la exposición a ISRS. Estos datos sugieren que la exposición neonatal a la CTM puede inducir cambios de larga duración en la formación del hipocampo en adultos, y estos efectos parecen dirigirse preferentemente a los machos.

Animals , Male , Female , Pregnancy , Rats , Prenatal Exposure Delayed Effects , Citalopram/pharmacology , Hippocampus/drug effects , Antidepressive Agents/pharmacology , Autistic Disorder/chemically induced , Behavior, Animal/drug effects , Citalopram/adverse effects , Cell Count , Sex Factors , Rats, Sprague-Dawley , Pyramidal Cells/drug effects , Hippocampus/cytology , Hippocampus/growth & development , Animals, Newborn , Antidepressive Agents/adverse effects
Rev. bras. cir. cardiovasc ; 34(3): 290-296, Jun. 2019. tab, graf
Article in English | LILACS | ID: biblio-1013469


Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.

Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Saphenous Vein/drug effects , Saphenous Vein/transplantation , Tranylcypromine/pharmacology , Fluoxetine/pharmacology , Amitriptyline/pharmacology , Antidepressive Agents/pharmacology , Reference Values , Vasodilation/drug effects , Endothelium, Vascular/drug effects , Coronary Artery Bypass/methods , Analysis of Variance , Transplants/drug effects , Venlafaxine Hydrochloride/pharmacology , Muscle, Smooth, Vascular/drug effects
Hosp. Aeronáut. Cent ; 12(2): 125-32, 2017.
Article in Spanish | LILACS, BINACIS | ID: biblio-911007


Introducción: El trastorno de la personalidad (TLP) afecta al 1-2% de la población adulta y aproximadamente al 20% de los pacientes hospitalizados por causas psiquiátricas. La tasa de mortalidad por suicidio alcanza el 10%, y se destacan las conductas suicidas que alcanzan el 84% de los pacientes, siendo éstas muy prevalentes en la consultas en los servicios de emergencia. El tratamiento psicofarmacológico aplicado en estos pacientes es uno de los abordajes clínicos que más incertidumbre generan debido a la falta de protocolos terapéuticos que cubran todas las dimensiones centrales de la personalidad. Objetivos: El objetivo del presente artículo es realizar una revisión bibliográfica sobre la utilidad de antipsicóticos de segunda generación, estabilizadores del ánimo y antidepresivos para el tratamiento farmacológico aplicado a la clínica de pacientes con diagnóstico de trastorno límite de la personalidad, con especificación de la evidencia científica para cada grupo farmacológico. Material y Método: Revisión y comparación bibliográfica sobre el uso y utilización de 3 grupos psicofarmacológicos (antipsicóticos de segunda generación, estabilizadores del ánimo y antidepresivos)para el tratamiento de pacientes con diagnóstico de TLP, con especificación de los indicadores y resultados de trabajos de medicina basada en la evidencia. Resultados: Según la revisión sistemática en ensayos clínicos con antipsicóticos (primera y segunda generación), estabilizadores del estado de ánimo y antidepresivos se hallaron mayores beneficios con el uso de estabilizadores del estado de ánimo (topiramato, lamotrigina y valproato de sodio) y antipsicóticos de segunda generación (aripiprazol y olanzapina). La consistencia es baja ya que el tamaño muestral fue pequeño o fue realizado mediante reportes de casos. Asimismo, la duración de los estudios varió de 5 a 24 semanas (duración promedio 12 semanas) y analizaron datos de 1714 participantes, con muestras heterogéneas en los estudios (entre 16 y 314 participantes).Conclusión: Suponemos que se debería profundizar en el abordaje de los síntomas borderline, básicamente investigaciones longitudinales a largo plazo (superior al año) con mayor número de pacientes, instrumentos de evaluación validados y tener en cuenta diseños para la traslación de resultados en contexto asistencial

Introduction: Personality disorder affects 1-2% of adult population and almost 20% of hospitalized patients for psychiatric causes. Mortality rate by suicide is almost 10%, and suicidal behaviour stand out in 84% of patients, being very prevalent in emergency service. Psicopharmacologic treatment applied to those patients is one of the approaches that more uncertainty generates because of the absence of therapeutic protocols that cover all the central dimensions of the personality. Objectives: to make a bibliographic review about second generation antipsychotics utility, mood stabilizers and antidepressants applied to patients with diagnosis of borderline personality disorder, with scientific evidence specification for each pharmacological group. Material and Method: Bibliographic review and comparison about use and utilization of three psicopharmacologic groups (second generation antipsychotics, mood stabilizers and antidepressant) for patients with borderline personality disorder treatment, with indicators specification and evidence-based medicine works results. Results: According to systematic review in clinical essays with antipsychotics (first and second generation), mood stabilizers and antidepressants, it was found more benefits with mood stabilizers (topiramate, lamotrigine and sodium valproate) and second generation antipsychotics (aripiprazole and olanzapine). The consistency is low because of the sample size or it was made with cases reports. Likewise, studies duration were between 5 and 24 weeks (average duration: 12 weeks) and 1714 data patients ́ were analysed, with heterogeneous sample (between 16 and 314). Conclusions: We assume we should deepen in borderline symptoms average with long term longitudinal studies (more than a year) with a bigger number of patients, validated evaluation instruments and take into account designs for results translation in an assistance context.

Antipsychotic Agents/therapeutic use , Borderline Personality Disorder/drug therapy , Borderline Personality Disorder/therapy , Antidepressive Agents/therapeutic use , Antipsychotic Agents/pharmacology , Evidence-Based Medicine , Antidepressive Agents/pharmacology
Rev. med. (Säo Paulo) ; 96(2): 103-115, 2017. ilus, tab
Article in English | LILACS | ID: biblio-868082


Introduction: Data have supported the influence of inflammation in the pathophysiology of depression and also the influence of depression in the development of a pro-inflammatory state. Major depressive disorder (MDD), the core depressive condition, has selective serotonin reuptake inhibitors (SSRI) as its first line pharmacological treatment. Efforts have been made to identify predictive factors for the responsiveness to SSRI. Therefore, we conducted this review to evaluate the hypothesis that baseline levels of inflammatory markers predict the responsiveness of MDD to SSRI treatment. Methods: A search in the PubMed database was made including the keywords ("SSRI" or "sertraline" or "citalopram" or "fluvoxamine" or "escitalopram" or "fluoxetine" or "paroxetine") and ("cytokines" or "CRP" or "TNF" or "inflammatory") and ("major depressive disorder" or "major depression"). Results: The search retrieved 245 manuscripts, from which 12 fulfilled our inclusion criteria. The analysis of these manuscripts suggested that high levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and c-reactive protein (CRP) at baseline might predict low responsiveness of MDD to SSRI treatment. Confounders such as cognitive impairment, chronicity and severity of depression, melancholic subtype, age and gender were not systematically included in the studies. Conclusion: Findings of this review suggest that high levels of pro-inflammatory markers at baseline might predict low responsiveness of MDD to SSRI treatment. Studies with adequate control for confounders are needed.

A influência da inflamação na fisiopatologia da depressão e o papel da depressão no desenvolvimento de um estado pró-inflamatório têm sido apoiados por diversos estudos. O transtorno depressivo maior (TDM), principal diagnóstico de depressão, tem os inibidores seletivos da recaptação de serotonina (ISRS) como tratamento farmacológico de primeira linha. Esforços têm sido feitos para identificar fatores preditivos da responsividade ao tratamento antidepressivo os ISRS. Portanto, esta revisão tem como objetivo avaliar a hipótese de que níveis basais de marcadores inflamatórios predizem a responsividade do TDM ao tratamento com ISRS. Métodos: Pesquisamos o banco de dados PubMed, incluindo as palavras-chave ("ISRS" ou "sertralina" ou "citalopram" ou "fluvoxamina" ou "escitalopram" ou "fluoxetina" ou "paroxetina") e ("citocinas" ou "CRP" ou "TNF" ou "inflamatório") e ("transtorno depressivo maior" ou "depressão maior"). Resultados:A pesquisa identificou 245 manuscritos, dos quais 12 satisfizeram os critérios de inclusão e exclusão e foram incluídos nesta revisão. A análise destes manuscritos sugeriu que níveis elevados de interleucina 6 (IL-6), interleucina 1ß (IL-1ß), fator de necrose tumoral ­ alfa (TNF-α) e proteína C-reativa (PCR) na avaliação basal podem prever baixa responsividade da depressão ao tratamento com ISRS. Fatores de confusão como deficiência cognitiva, cronicidade e gravidade da depressão, subtipo melancólico, idade e sexo, não foram sistematicamente incluídos nos estudos. Conclusão: Os achados desta revisão sugerem que níveis elevados de marcadores pró-inflamatórios na avaliação basal podem predizer baixa responsividade do TDM ao tratamento com ISRS. Estudos com controle adequado para fatores de confusão são necessários.

Biomarkers , Cytokines , Depression/drug therapy , Inflammation , Selective Serotonin Reuptake Inhibitors , Antidepressive Agents/pharmacology , Predictive Value of Tests
Rev. méd. Chile ; 144(10): 1326-1335, oct. 2016. ilus, tab
Article in Spanish | LILACS | ID: biblio-845448


Tamoxifen (Tmf), is a standard of care for women with estrogen receptor positive (ER+) breast cancer. Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Antidepressive agents (AD) are often prescribed to women with breast cancer not only for depression, but also for anxiety and hot flashes. Some AD are substrates or inhibitors of the Tmf metabolic pathway. Therefore there may be interactions when Tmf and AD are prescribed simultaneously. Oncologic protection afforded by Tmf may become less effective or null when AD are indicated, especially in poor metabolizing patients. We performed an update of the literature about the criteria for choosing AD in women receiving Tmf. Tricyclic AD, paroxetine and fluoxetine should be avoided in patients receiving Tmf, because they are strong inhibitors of CYP2D6. Bupropion, duloxetine and sertraline are only moderate inhibitors of the cytochrome and are not contraindicated. Citalopram, desvenlafaxine, escitalopram, milnacipran and venlafaxine are recommended, because they do not influence the metabolism and clinical efficacy of Tmf and have fewer drug interactions. However, other additional pharmacological and clinical issues should be considered when choosing an antidepressant in women with breast cancer.

Humans , Female , Tamoxifen/pharmacology , Breast Neoplasms/drug therapy , Antineoplastic Agents, Hormonal/pharmacology , Antidepressive Agents/pharmacology , Tamoxifen/metabolism , Breast Neoplasms/metabolism , Risk Factors , Antineoplastic Agents, Hormonal/metabolism , Cytochrome P-450 CYP2D6/drug effects , Drug Interactions , Genotype , Antidepressive Agents/metabolism