RESUMEN
Antidepressant response is a multifactorial process related to biological and environmental factors, where brain-derived neurotrophic factor (BDNF) may play an important role in modulating depressive and anxious symptoms. We aimed to analyze how BDNF impacts antidepressant response, considering the levels of anxiety. METHODS: A total of 40 depressed adults were included. We evaluated initial serum BDNF, anxiety through the State-Trait Anxiety Inventory (STAI), and the severity of depressive symptoms by the Hamilton Depression Rating Scale (HDRS). Participants received antidepressant treatment for 8 weeks, and response to treatment was evaluated according to the final HDRS scores. RESULTS: Basal BDNF was higher in responders compared to non-responder depressed patients, in addition to being inversely associated with the severity of anxiety and depression. CONCLUSIONS: Baseline BDNF serum is an adequate predictive factor for response to antidepressant treatment with SSRI, with lower pre-treatment levels of BDNF associated with higher anxiety symptoms after treatment. Stress levels could influence the response to treatment, but its association was not conclusive.
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Antidepresivos , Ansiedad , Factor Neurotrófico Derivado del Encéfalo , Depresión , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antidepresivos/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/sangre , Depresión/tratamiento farmacológico , Depresión/sangre , Estrés Psicológico/tratamiento farmacológico , Resultado del Tratamiento , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
IMPORTANCE: Seasonal humor disorders are prone to have a link with daylight exposure. However, the effect of external light on nonseasonal disorders remains unclear. Evidence is lacking for the validity of bright light therapy (BLT) as an adjunctive treatment for these patients. OBJECTIVE: To assess BLT effectiveness as an adjunctive treatment for nonseasonal depressive disorders. DATA SOURCES: In March 2024, a comprehensive search was performed of publications in the MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) evaluating BLT effects in patients with nonseasonal depression. STUDY SELECTION: RCTs published since 2000 were eligible. Comparisons between BLT and dim red light or antidepressant monotherapy alone were considered for inclusion. DATA EXTRACTION AND SYNTHESIS: Using the systematic review approach on RCTs published from January 1, 2000, through March 25, 2024, differences between patients treated with and without BLT were estimated using the Mantel-Haenszel method; heterogeneity was assessed using I2 statistics. MAIN OUTCOMES AND MEASURES: Remission of symptoms, response to treatment rates, and depression scales were assessed. RESULTS: In this systematic review and meta-analysis of 11 unique trials with data from 858 patients (649 female [75.6%]), statistically significant better remission and response rates were found in the BLT group (remission: 40.7% vs 23.5%; odds ratio [OR], 2.42; 95% CI, 1.50-3.91; P <.001; I2 = 21%; response: 60.4% vs 38.6%; OR, 2.34; 95% CI, 1.46-3.75; P <.001; I2 = 41%). With BLT, subgroup analysis based on follow-up times also showed better remission (<4 weeks: 27.4% vs 9.2%; OR, 3.59; 95% CI, 1.45-8.88; P = .005; I2 = 0% and >4 weeks: 46.6% vs 29.1%; OR, 2.18; 95% CI, 1.19-4.00; P = .01; I2 = 47%) and response (<4 weeks: 55.6% vs 27.4%; OR, 3.65; 95% CI, 1.81-7.33; P <.001; I2 = 35% and >4 weeks: 63.0% vs 44.9%; OR, 1.79; 95% CI, 1.01-3.17; P = .04; I2 = 32%) rates. CONCLUSIONS AND RELEVANCE: Results of this systematic review and meta-analysis reveal that BLT was an effective adjunctive treatment for nonseasonal depressive disorders. Additionally, results suggest that BLT may improve the response time to the initial treatment.
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Humanos , Masculino , Femenino , Fototerapia , Trastorno Depresivo , Antidepresivos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Aim: This study reassesses the efficacy and safety of antidepressants in treating nonspecific chronic low back pain (NCLBP).Materials & methods: A systematic review was conducted following PRISMA guidelines, including randomized clinical trials (RCTs) from PubMed, Embase, Scopus, LILACS, SciELO and Cochrane CENTRAL, published through August 2024. Studies compared antidepressants with placebo or active comparators. The primary outcomes were pain relief and quality of life. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42023307516.Results: Nine RCTs involving 1758 patients were analyzed. The antidepressants examined included duloxetine, escitalopram, bupropion, amitriptyline, imipramine and desipramine. Duloxetine 60 mg significantly reduced pain (MD = -0.57; 95% CI = -0.78 to -0.36) and improved quality of life compared with placebo, with side effects that were generally tolerable. Notably, higher doses of duloxetine (120 mg) were associated with an increase in adverse events. However, other antidepressants like amitriptyline and escitalopram demonstrated only modest or inconsistent effects.Conclusion: Duloxetine at 60 mg provides consistent pain relief and improves the quality of life in NCLBP, but higher doses increase adverse events. Escitalopram might offer modest benefits but should be considered a third-line treatment. Other antidepressants, such as amitriptyline, bupropion, imipramine and desipramine, have limited evidence supporting their efficacy and are associated with adverse effects.
Chronic lower back pain is a condition that persists for a long time and can be difficult to manage. While the exact cause isn't always clear, it affects many people and can be difficult to manage. Doctors sometimes prescribe antidepressants, which are typically used for treating depression, but they may also help to reduce pain by influencing how the brain processes it.In this paper, we examined several studies to determine whether these antidepressants are effective in treating chronic lower back pain. We analyzed nine studies involving 1758 participants who were treated with different medications: bupropion, duloxetine, escitalopram, amitriptyline, imipramine and desipramine.Among these medications, duloxetine stood out as the most effective. It not only helped to relieve pain but also improved the participants' ability to carry out daily activities. Additionally, duloxetine had fewer side effects than some of the other medications, although it can still cause mild issues such as nausea.In conclusion, duloxetine appears to be a promising option for managing chronic lower back pain, as long as the appropriate dosage is used to balance pain relief and side effects.
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Antidepresivos , Dolor Crónico , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/tratamiento farmacológico , Antidepresivos/uso terapéutico , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Dolor Crónico/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Calidad de Vida , Clorhidrato de Duloxetina/uso terapéutico , Clorhidrato de Duloxetina/administración & dosificaciónRESUMEN
In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.
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Analgésicos , Antidepresivos , Flavonoides , Morfina , Animales , Morfina/farmacología , Morfina/uso terapéutico , Ratones , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/química , Masculino , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/química , Flavonoides/farmacología , Flavonoides/uso terapéutico , Flavonoides/química , Dolor/tratamiento farmacológico , Manejo del Dolor/métodos , Actividad Motora/efectos de los fármacosRESUMEN
Depression is a highly prevalent neuropsychiatric disorder worldwide. One currently accepted hypothesis of this pathogenesis is the hypothalamic-pituitary-adrenal axis dysfunction, which involves oxidative stress and brain damage. Therefore, antioxidants, such as phenolic compounds, could be used in depression. In this study, we investigated the antidepressant-like and antioxidant effects of an aqueous extract of the leaves of three species of the genus Psidium, Myrtaceae family, in mice. The exotic Psidium guajava L. and the natives Psidium guineense Sw. and Psidium cattleianum Sabine (10, 1, and 0.1 mg/kg, respectively) and fluoxetine (10 mg/kg) were administered orally (p.âo.) once daily for 21 days, with or without corticosterone (20 mg/kg). After behavioral assessments (tail suspension, splash, and open-field tests), the hippocampus, prefrontal cortex, liver, kidneys, and plasma were examined to determine the oxidative stress status. The three extracts and fluoxetine treatment decreased the immobility time and counteracted the oxidative stress induced by corticosterone administration. The phenolic compounds identified as major components of the extracts, quercetin in P. guajava and P. guineense and o-coumaric acid in P. cattleianum, may be involved in the biological activities. Therefore, the aqueous leaf extracts of P. guajava, P. cattleianum, and P. guineense could be potential antidepressants helpful in treating depression and other diseases with elevated nitro-oxidative stress.
Asunto(s)
Antidepresivos , Corticosterona , Depresión , Estrés Oxidativo , Extractos Vegetales , Psidium , Animales , Psidium/química , Ratones , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Corticosterona/sangre , Antidepresivos/farmacología , Masculino , Depresión/tratamiento farmacológico , Brasil , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Hojas de la Planta/química , Fluoxetina/farmacologíaRESUMEN
Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/ßCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/ßCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/ßCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1ß, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/ßCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/ßCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1ß levels. The effects of the NEO/ßCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress.
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Antidepresivos , Depresión , Estrés Psicológico , beta-Ciclodextrinas , Animales , beta-Ciclodextrinas/farmacología , beta-Ciclodextrinas/química , Ratones , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Masculino , Estrés Psicológico/tratamiento farmacológico , Depresión/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ansiedad/tratamiento farmacológico , Ansiolíticos/farmacología , Natación , Administración OralRESUMEN
Antidepressants are the third most prescribed drug class, and most prescriptions are not performed by specialists. This study aimed to evaluate primary health care (PHC) physicians' self-perceived confidence in prescribing antidepressants. This is a cross-sectional study with PHC physicians in the municipality of Salvador, Bahia State, Brazil. Psychiatrists or psychiatry residents were excluded. The self-assessment of confidence and the collection of participants' characteristics was carried out by an online questionnaire. Categorical variables were presented in absolute and relative frequencies. Continuous variables were described as means or medians according to their normality distribution. Of 447 physicians, the sample consisted of 55 participants. Their mean age was 37.2 ± 12.8 years. Most physicians (75%) claimed confidence in prescribing antidepressants. Self-perceived confidence remained predominant in scenarios with older adults (69.2%) and patients with general comorbidities (65.4%). A minority showed confidence to prescribe antidepressants to children/adolescents (19.2%) and pregnant women (26.9%). For 80.4% of participants, selective serotonin reuptake inhibitors were the most trusted pharmacological class. Referral to the Psychosocial Care Center was the most reported strategy in cases of insecure prescription (32%). To the best of our knowledge, this is the first study to address such an issue. Thus, it can contribute to more assertive health education actions for PHC physicians.
Os antidepressivos são a terceira classe medicamentosa mais prescrita, sendo que a maioria das prescrições não é realizada por especialistas. O objetivo do estudo é avaliar a autopercepção de confiança na prescrição de antidepressivos por médicos da atenção primária à saúde (APS). Foi realizado estudo de corte transversal de médicos atuantes na APS da cidade de Salvador, Bahia, Brasil. Foram excluídos psiquiatras ou residentes de psiquiatria. A autoavaliação da confiança, assim como a coleta de características dos participantes foi realizada por meio de questionário online. Variáveis categóricas foram descritas em termos de frequência absoluta e relativa. Variáveis contínuas foram descritas como média ou mediana, conforme distribuição de normalidade. No contexto total de 447 médicos, a amostra foi composta por 55 participantes. A média de idade foi de 37,2 (±12,8) anos. A maioria dos médicos (75%) reconheceu-se confiante na prescrição de antidepressivos. A autopercepção de confiança manteve-se predominante em cenários de pacientes idosos (69,2%) e portadores de comorbidades gerais (65,4%). A minoria mostrou confiança para prescrever antidepressivos a crianças/adolescentes (19,2%) e gestantes (26,9%). Para 80,4% dos participantes, os inibidores seletivos da recaptação de serotonina foram a classe farmacológica de maior confiança. O encaminhamento para o Centro de Atenção Psicossocial foi a estratégia mais referida em casos de insegurança na prescrição (32%). Até onde se sabe, esse é o primeiro estudo a abordar tal questão. Por essa razão, ele pode contribuir para a construção de ações de educação em saúde mais assertivas voltadas a médicos da APS.
Los antidepresivos son la tercera clase de medicamentos más prescritos, y la mayoría de las prescripciones no son realizadas por especialistas. El objetivo del estudio es evaluar la autopercepción de confianza en la prescripción de antidepresivos por parte de los médicos de atención primaria de salud (APS). Corte transversal de médicos que trabajan en la APS de la ciudad de Salvador, Bahia, Brasil. Se excluyeron a los psiquiatras o residentes de psiquiatría. La autoevaluación de la confianza, así como la recolección de las características de los participantes, fue realizada a través de un cuestionario online. Las variables categóricas se describieron en términos de frecuencia absoluta y relativa. Las variables continuas se describieron como media o mediana, según la distribución de normalidad. En el contexto total de 447 médicos, la muestra estaba formada por 55 participantes. La edad promedio fue de 37,2 (±12,8) años. La mayoría de los médicos (75%) se reconocieron confiados en la prescripción de antidepresivos. La autopercepción de confianza se mantuvo predominante en los escenarios de pacientes ancianos (69,2%) y portadores de comorbilidades generales (65,4%). La minoría mostró confianza para prescribir antidepresivos a niños/adolescentes (19,2%) y mujeres embarazadas (26,9%). Para el 80,4% de los participantes, los inhibidores selectivos de la recaptación de serotonina eran la clase farmacológica de mayor confianza. El encaminamiento para el Centro de Atención Psicosocial fue la estrategia más mencionada en los casos de inseguridad en la prescripción (32%). Hasta donde se sabe, este es el primer estudio que aborda este tema. Por esa razón, puede contribuir para la construcción de acciones de educación en salud más asertivas dirigidas a los médicos de la APS.
Asunto(s)
Antidepresivos , Pautas de la Práctica en Medicina , Atención Primaria de Salud , Humanos , Femenino , Estudios Transversales , Masculino , Adulto , Antidepresivos/uso terapéutico , Atención Primaria de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Persona de Mediana Edad , Brasil , Encuestas y Cuestionarios , Prescripciones de Medicamentos/estadística & datos numéricosRESUMEN
Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized. To address this question, we used the EAE model of MS, behavioral tests, immunofluorescence, immunohistochemistry, western blot, and 16 S rRNA sequencing. Here, we showed that depressive-like behavior in Experimental Autoimmune Encephalomyelitis (EAE) mice is due to neuroinflammation, reduced synaptic plasticity, dysfunction in glutamatergic neurotransmission, glucocorticoid receptor (GR) resistance, increased blood-brain barrier (BBB) permeability, and immune cell infiltration to the CNS, as well as inflammation, increased intestinal permeability, and immune cell infiltration in the distal colon. Furthermore, 16 S rRNA sequencing revealed that behavioral dysfunction in EAE mice is associated with changes in the gut microbiota, such as an increased abundance of Firmicutes and Saccharibacteria and a reduction in Proteobacteria, Parabacteroides, and Desulfovibrio. Moreover, we detected an increased abundance of Erysipelotrichaceae and Desulfovibrionaceae and a reduced abundance of Lactobacillus johnsonii. Surprisingly, we showed that Tadalafil likely exerts antidepressant-like effects by targeting all aforementioned disease aspects. In conclusion, our work demonstrated that anxiety- and depressive-like behavior in EAE is associated with a plethora of neuroimmune and gut microbiota-mediated mechanisms and that Tadalafil exerts antidepressant-like effects probably by targeting these mechanisms. Harnessing the knowledge of these mechanisms of action of Tadalafil is important to pave the way for future clinical trials with depressed patients.
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Ansiolíticos , Antidepresivos , Eje Cerebro-Intestino , Depresión , Encefalomielitis Autoinmune Experimental , Inhibidores de Fosfodiesterasa 5 , Tadalafilo , Animales , Femenino , Ratones , Ansiolíticos/administración & dosificación , Antidepresivos/administración & dosificación , Autoinmunidad/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Depresión/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Endogámicos C57BL , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Tadalafilo/administración & dosificaciónRESUMEN
The present study aimed to evaluate the protective potential of carvacrol against depressive-like behavior and cognitive impairment prompted by chronic unpredictable mild stress (CUMS) in mice. The animals were divided into six groups: Control (non-stressed), CARV (carvacrol at 50â¯mg/kg, p.o.), FLU (fluoxetine at 10â¯mg/kg, p.o.), CUMS (stressed), CUMS + CARV and CUMS + FLU, and the groups with CUMS were subjected to different stressors for 28 days. After treatment, mice underwent behavioral testing (open field, forced swimming, sucrose preference, social interaction, novel object recognition and Y-maze) and brain areas were removed for oxidative stress (MDA, nitrite/nitrate and GSH levels) and cytokine (IL-1ß and TNF-α) content assays. The results revealed that CARV administration reversed depressive-like behavior and significantly ameliorated the cognitive deficit induced by CUMS, as well as was able to attenuate oxidative stress (decreased MDA and nitrite/nitrate levels and increased GSH levels). In addition, a significant reduction in hippocampal IL-1ß and TNF-α levels was observed, demonstrating a potential anti-neuroinflammatory activity. Taken together, the antioxidant and anti-inflammatory activities observed in this study indicate that CARV is a promising drug for antidepressant treatment.
Asunto(s)
Conducta Animal , Disfunción Cognitiva , Cimenos , Depresión , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Estrés Psicológico , Animales , Estrés Oxidativo/efectos de los fármacos , Ratones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Depresión/etiología , Masculino , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Cimenos/farmacología , Cimenos/administración & dosificación , Conducta Animal/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Antidepresivos/farmacología , Antidepresivos/administración & dosificación , Antioxidantes/farmacología , Fluoxetina/farmacología , Fluoxetina/administración & dosificación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Interleucina-1beta/metabolismoRESUMEN
Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1ß and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.
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Ansiedad , Eje Cerebro-Intestino , Disfunción Cognitiva , Depresión , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Péptidos Similares al Glucagón , Ratones Endogámicos C57BL , Animales , Péptidos Similares al Glucagón/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/metabolismo , Ratones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Depresión/tratamiento farmacológico , Depresión/psicología , Depresión/metabolismo , Masculino , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Ansiedad/etiología , Microbioma Gastrointestinal/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/psicología , Diabetes Mellitus Experimental/metabolismo , Modelos Animales de Enfermedad , Antidepresivos/farmacología , Antidepresivos/uso terapéuticoRESUMEN
Depression and anxiety are recognized as the most common mental diseases worldwide. New approaches have considered different therapeutic targets, such as oxidative stress and the inflammation process, due to their close association with the establishment and progression of mental diseases. In the present study, we evaluated the antioxidant and anti-inflammatory activities of the methanolic extracts of the plant species Heteropterys brachiata and Heteropterys cotinifolia and their main compounds, chlorogenic acid and rutin, as potential complementary therapeutic tools for the treatment of anxiety and depression, since the antidepressant and anxiolytic activities of these methanolic extracts have been shown previously. Additionally, we also evaluated their inhibitory activity on the enzyme acetylcholinesterase (AChE). Our results revealed that both species exhibited potent antioxidant activity (>90%) through the TBARS assay, while by means of the DPPH assay, only H. cotinifolia exerted potent antioxidant activity (>90%); additionally, low metal chelating activity (<40%) was detected for all samples tested in the ferrozine assay. The methanolic extracts of H. brachiata and H. cotinifolia exhibited significant anti-inflammatory activities in the TPA-induced ear edema, while only H. cotinifolia exerted significant anti-inflammatory activities in the MPO assay (>45%) and also exhibited a higher percentage of inhibition on AChE of even twice (>80%) as high as the control in concentrations of 100 and 1000 µg/mL. Thus, the potent antioxidant and inflammatory properties and the inhibition of AChE may be involved in the antidepressant activities of the species H. cotinifolia, which would be positioned as a candidate for study in drug development as an alternative in the treatment of depression.
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Antiinflamatorios , Antioxidantes , Extractos Vegetales , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Animales , Acetilcolinesterasa/metabolismo , Antidepresivos/farmacología , Antidepresivos/química , Antidepresivos/uso terapéutico , Ratones , MéxicoRESUMEN
OBJECTIVE: Fibromyalgia (FM) subjects are treated with antidepressant agents; in most cases, these drugs lose efficacy or have adverse effects. Ketamine is an anesthetic drug used in FM in some studies. This article aims to systematically review the safety and efficacy of ketamine in fibromyalgia (FM) patients. MATERIALS AND METHODS: We systematically searched articles on FM and ketamine published at Pubmed from 1966 to 2021. This study was registered at PROSPERO. RESULTS: There were only 6 articles published in this field, with a total of 115 patients. The female sex was predominant (88 to 100%). The age varied from 23 to 53 years old. Disease duration ranged from 1 month to 28 years. The dosage of ketamine changed from 0.1 mg/kg-0.3-0.5 mg/kg in intravenous infusion (4/5) and subcutaneous application (1/5). Regarding outcomes, the Visual analog scale (VAS) before ketamine was from 59 to 100 mm and after treatment from 2 to 95 mm. Most short-term studies had a good response. Only the study with 8 weeks of follow-up did not observe a good response. Side effects were common; all appeared during the infusion and disappeared after a few minutes of the ketamine injection. CONCLUSIONS: The present study demonstrates the effectiveness and safety of ketamine in FM patients in the short term. Although, more studies, including long-term follow-up studies, are still needed.
Asunto(s)
Fibromialgia , Ketamina , Ketamina/uso terapéutico , Ketamina/administración & dosificación , Ketamina/efectos adversos , Fibromialgia/tratamiento farmacológico , Humanos , Analgésicos/uso terapéutico , Analgésicos/efectos adversos , Analgésicos/administración & dosificación , Femenino , Masculino , Adulto , Persona de Mediana Edad , Antidepresivos/uso terapéutico , Antidepresivos/efectos adversos , Dimensión del Dolor , Infusiones Intravenosas , Resultado del TratamientoRESUMEN
RATIONALE: The compound 5-((4-methoxyphenyl)thio)benzo[c][1,2,5]thiadiazole (MTDZ) has recently been shown to inhibit in vitro acetylcholinesterase activity, reduce cognitive damage, and improve neuropsychic behavior in mice, making it a promising molecule to treat depression. OBJECTIVES: This study investigated the antidepressant-like action of MTDZ in mice and its potential mechanisms of action. RESULTS: Molecular docking assays were performed and suggested a potential inhibition of monoamine oxidase A (MAO-A) by MTDZ. The toxicity study revealed that MTDZ displayed no signs of toxicity, changes in oxidative parameters, or alterations to biochemistry markers, even at a high dose of 300 mg/kg. In behavioral tests, MTDZ administration reduced immobility behavior during the forced swim test (FST) without adjusting the climbing parameter, suggesting it has an antidepressant effect. The antidepressant-like action of MTDZ was negated with the administration of 5-HT1A, 5-HT1A/1B, and 5-HT3 receptor antagonists, implying the involvement of serotonergic pathways. Moreover, the antidepressant-like action of MTDZ was linked to the NO system, as L-arginine pretreatment inhibited its activity. The ex vivo assays indicated that MTDZ normalized ATPase activity, potentially linking this behavior to its antidepressant-like action. MTDZ treatment restricted MAO-A activity in the cerebral cortices and hippocampi of mice, proposing a selective inhibition of MAO-A associated with the antidepressant-like effect of the compound. CONCLUSIONS: These findings suggest that MTDZ may serve as a promising antidepressant agent due to its selective inhibition of MAO-A and the involvement of serotonergic and NO pathways.
Asunto(s)
Antidepresivos , Simulación del Acoplamiento Molecular , Monoaminooxidasa , Tiadiazoles , Animales , Masculino , Tiadiazoles/farmacología , Tiadiazoles/administración & dosificación , Ratones , Antidepresivos/farmacología , Antidepresivos/administración & dosificación , Femenino , Monoaminooxidasa/metabolismo , Depresión/tratamiento farmacológico , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/administración & dosificación , Conducta Animal/efectos de los fármacos , Administración OralRESUMEN
Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.
Asunto(s)
Antidepresivos , Modelos Animales de Enfermedad , Ketamina , Receptores de N-Metil-D-Aspartato , Ketamina/farmacología , Ketamina/uso terapéutico , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Humanos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Antagonistas de Aminoácidos Excitadores/farmacología , Esquizofrenia/tratamiento farmacológico , Depresión/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. METHODS: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. RESULTS: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. CONCLUSION: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.
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Antidepresivos , Ketamina , Actividad Motora , Natación , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Ratones , Masculino , Ketamina/farmacología , Ketamina/análogos & derivados , Actividad Motora/efectos de los fármacos , Factores de Tiempo , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Reproducibilidad de los ResultadosRESUMEN
Sleep is a fundamental state for maintaining the organism homeostasis. Disruptions in sleep patterns predispose to the appearance of memory impairments and mental disorders, including depression. Recent pre-clinical studies have highlighted the antidepressant-like properties of the synthetic compound 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1). To further investigate the neuromodulatory effects of SeBZF1, this study aimed to assess its therapeutic efficacy in ameliorating neurobehavioral impairments induced by sleep deprivation (SD) in mice. For this purpose, a method known as multiple platforms over water was used to induce rapid eye movement (REM) SD. Two hours after acute SD (24 h), male Swiss mice received a single treatment of SeBZF1 (5 mg/kg, intragastric route) or fluoxetine (a positive control, 20 mg/kg, intraperitoneal route). Subsequently, behavioral tests were conducted to assess spontaneous motor function (open-field test), depressive-like behavior (tail suspension test), and memory deficits (Y-maze test). Brain structures were utilized to evaluate oxidative stress markers, monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities. Our findings revealed that SD animals displayed depressive-like behavior and memory impairments, which were reverted by SeBZF1 and fluoxetine treatments. SeBZF1 also reverted the increase in lipoperoxidation levels and glutathione peroxidase activity in the pre-frontal cortex in mice exposed to SD. Besides, the increase in hippocampal AChE activity induced by SD was overturned by SeBZF1. Lastly, cortical MAO-B activity was reestablished by SeBZF1 in mice that underwent SD. Based on the main findings of this study, it can be inferred that the compound SeBZF1 reverses the neurobehavioral alterations induced by sleep deprivation in male Swiss mice.
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Benzofuranos , Privación de Sueño , Animales , Masculino , Ratones , Privación de Sueño/tratamiento farmacológico , Benzofuranos/farmacología , Benzofuranos/uso terapéutico , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.
Asunto(s)
Liposomas , Nanocápsulas , Paroxetina , Animales , Paroxetina/administración & dosificación , Paroxetina/farmacología , Paroxetina/química , Nanocápsulas/química , Ratones , Chlorocebus aethiops , Masculino , Células Vero , Tamaño de la Partícula , Liberación de Fármacos , Depresión/tratamiento farmacológico , Suspensión Trasera , Antidepresivos/administración & dosificación , Antidepresivos/química , Antidepresivos/farmacología , Antidepresivos de Segunda Generación/administración & dosificación , Antidepresivos de Segunda Generación/química , Antidepresivos de Segunda Generación/farmacología , Conducta Animal/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
Therapeutics for suicide management is limited, taking weeks to work. This open-label clinical trial with 18 treatment-resistant depressive patients tested subcutaneous esketamine (8 weekly sessions) for suicidality. We noted a rapid and enduring effect of subcutaneous esketamine, lasting from one week to six months post-treatment, assessed by the Beck Inventory for Suicidality (BSI). There was an immediate drop in suicidality, 24 h following the initial dose, which persisted for seven days throughout the eight-week dosing period. Additionally, this study is the first to examine a six-month follow-up after multiple administrations of subcutaneous esketamine, finding consistently lower levels of suicidality throughout this duration. Conversely, suicidality also was measured along the 8-weeks of treatment by a psychiatrist using the Montgomery-Asberg Depression Rating Scale (MADRS), which showed significant reduction only after two treatment sessions expanding until the last session. Moreover, notably, 61% of patients achieved remission on suicidality (MADRS). These results suggest that weekly subcutaneous esketamine injections offer a cost-effective approach that induces a rapid and sustained response to anti-suicide treatment. This sets the stage for further, more controlled studies to corroborate our initial observations regarding the effects of SC esketamine on suicidality. Registered trial at: https://ensaiosclinicos.gov.br/rg/RBR-1072m6nv.
Asunto(s)
Antidepresivos , Trastorno Depresivo Resistente al Tratamiento , Ketamina , Ideación Suicida , Humanos , Ketamina/administración & dosificación , Ketamina/farmacología , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antidepresivos/administración & dosificación , Antidepresivos/farmacología , Inyecciones Subcutáneas , Estudios de Seguimiento , Factores de TiempoRESUMEN
Objetivo: Avaliar a prevalência de uso de medicamentos antidepressivos e alterações metabólicas em indivíduos HIV positivos submetidos a terapia antirretroviral (TARV) no vale do Paranhana - RS. Métodos: Trata-se de um estudo descritivo transversal de abordagem quantitativa, realizado por meio da coleta de dados de prontuários físicos mantidos na Vigilância em Saúde do município de Taquara/RS e dados de prontuários eletrônicos do município de Igrejinha/RS e Parobé/RS. Resultados: A amostra foi composta por 238 indivíduos, dos quais 122 indivíduos são do sexo masculino e 116 do sexo feminino, com idade entre 18 e 76 anos. Os participantes tiveram um tempo de diagnóstico e duração de tratamento entre 2 e 17 anos, sendo que a maioria realizava tratamento com a terapia antirretroviral - TARV de 1ª linha, porém havia um grande percentual de indivíduos em uso da terapia de 2ª linha (40,8%). Um número expressivo de indivíduos fazia uso de antidepressivos (15,1%) e ansiolíticos (10,9%). Em relação aos marcadores metabólicos, foi encontrada uma prevalência de 17,6 % de alterações nos níveis de triglicerídeos e 62,7 % de alterações nos níveis da lipoproteína de alta densidade HDL. Para as análises estratificadas pelas linhas de tratamento, o colesterol total demonstrou uma maior proporção de indivíduos na faixa de normalidade (P=0,007) no grupo tratado com a TARV de 1ª linha (Normal: 91, 70,0%), quando comparado aos que utilizavam tratamento de 2º linha (Normal: 61, 64,2%). Conclusão: A prevalência de hipertrigliceridemia em indivíduos HIV submetidos a TARV foi 17,6 %, e a de dislipidemia associada aos valores reduzidos de HDL é de 37, 3 %. (AU)
Objective: To assess the prevalence of antidepressant medication use and metabolic syndrome in HIV-positive patients undergoing antiretroviral therapy (ARV) in the Paranhana Valley, RS, Brazil. Methods: This is a descriptive cross-sectional study with a quantitative approach, conducted through the collection of data from physical medical records maintained in the Health Surveillance of the municipality of Taquara/RS and electronic medical records from the municipalities of Igrejinha/RS and Parobé/RS. Results: The sample consisted of 238 individuals with HIV, of which 122 were male and 116 were female, aged between 18 and 76 years. Participants had a diagnosis and treatment duration between 2 and 17 years, with the majority undergoing treatment with first-line antiretroviral therapy - ART, although there was a large percentage of individuals using second-line therapy (40.8%). A significant number of individuals were using antidepressants (15.1%) and anxiolytics (10.9%). Regarding metabolic markers, a prevalence of 17.6% of alterations in triglyceride levels and 62.7% of alterations in high-density lipoprotein - HDL levels was found. For the analyses stratified by treatment lines, total cholesterol showed a higher proportion of individuals in the normal range (P=0.007) in the group treated with first-line ART (Normal: 91, 70.0%) compared to those using second-line treatment (Normal: 61, 64.2%). Conclusion: The prevalence of hypertriglyceridemia in HIV patients undergoing ART was 17.6%, and the prevalence of dyslipidemia associated with reduced HDL values is 37.3%. (AU)
Objetivo: Evaluar la prevalencia del uso de medicamentos antidepresivos y alteraciones metabólicas en personas VIH positivos sometidos a terapia antirretroviral (TAR) en el Valle del Paranhana, RS, Brasil. Métodos: Se trata de un estudio descriptivo transversal con enfoque cuantitativo, realizado mediante la recopilación de datos de registros médicos físicos mantenidos en la Vigilancia en Salud del municipio de Taquara/RS y datos de registros médicos electrónicos de los municipios de Igrejinha/RS y Parobé/RS. Resultados: La muestra estuvo compuesta por 238 individuos con VIH, de los cuales 122 eran hombres y 116 mujeres, con edades entre 18 y 76 años. Los participantes tuvieron un tiempo de diagnóstico y duración del tratamiento entre 2 y 17 años, siendo la mayoría sometida a tratamiento con terapia antirretroviral de primera línea, aunque hubo un gran porcentaje de individuos utilizando terapia de segunda línea (40,8%). Un número significativo de individuos estaba usando antidepresivos (15,1%) y ansiolíticos (10,9%). En cuanto a los marcadores metabólicos, se encontró una prevalencia del 17,6% de alteraciones en los niveles de triglicéridos y del 62,7% de alteraciones en los niveles de lipoproteína de alta densidad - HDL. Para los análisis estratificados por líneas de tratamiento, el colesterol total mostró una mayor proporción de individuos en el rango normal (P=0,007) en el grupo tratado con terapia antirretroviral de primera línea (Normal: 91, 70,0%) en comparación con aquellos que usaban tratamiento de segunda línea (Normal: 61, 64,2%). Conclusión: La prevalencia de hipertrigliceridemia en personas VIH sometidos a TAR fue del 17,6%, y la prevalencia de dislipidemia asociada con valores reducidos de HDL es del 37,3%. (AU)
Asunto(s)
Terapia Antirretroviral Altamente Activa , Síndrome Metabólico , AntidepresivosRESUMEN
This study aimed to characterize the population pharmacokinetics of sertraline in Mexican patients with psychiatric and substance use disorders. Fifty-nine patients (13 to 76 years old) treated with doses of sertraline between 12.5 and 100 mg/day were included. Plasma sertraline concentrations were determined in blood samples and five of the main substances of abuse were determined by rapid tests in urine samples. Demographic, clinical, and pharmacogenetic factors were also evaluated. Population pharmacokinetic analysis was performed using NONMEM software with first-order conditional estimation method. A one-compartment model with proportional residual error adequately described the sertraline concentrations versus time. CYP2D6*2 polymorphism and CYP2C19 phenotypes significantly influenced sertraline clearance, which had a population mean value of 66 L/h in the final model. The absorption constant and volume of distribution were fixed at 0.855 1/h and 20.2 L/kg, respectively. The model explained 11.3% of the interindividual variability in sertraline clearance. The presence of the CYP2D6*2 polymorphism caused a 23.1% decrease in sertraline clearance, whereas patients with intermediate and poor phenotype of CYP2C19 showed 19.06% and 48.26% decreases in sertraline clearance, respectively. The model was internally validated by bootstrap and visual predictive check. Finally, stochastic simulations were performed to propose dosing regimens to achieve therapeutic levels that contribute to improving treatment response.