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1.
Artigo em Russo | MEDLINE | ID: mdl-34283536

RESUMO

The article presents the literature data that determine the place of antidepressants in the relief and maintenance therapy for recurrent depression (RD) and depression in the framework of bipolar affective disorder (BPAD) and provides a justification for their use in the presence of residual depressive symptoms during remission. There are several ways to achieve complete remission: determination of the nature of residual symptoms; identification of adverse side-effects that have occurred as a result of the therapy; the establishment of those symptoms that are subjectively perceived by the patient as interfering with his/her full life. The data on the effective use of agomelatin for maintenance therapy, both as monotherapy and in combination with other antidepressants, anticonvulsants and neuroleptics, in RD and BPAD are presented. The authors have analyzed the case histories of 29 outpatients with depressions of various origins (RDD, BPAD, prolonged psychogenic depression, organic affective disorder), who received agomelatin as part of complex and monotherapy for a long time (1 to 13 years), and justified the predictors of its efficacy.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno Depressivo Maior , Transtornos Psicóticos , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Masculino , Transtornos Psicóticos/tratamento farmacológico
2.
Artigo em Russo | MEDLINE | ID: mdl-34283542

RESUMO

The review briefly summarizes experimental and preclinical data of the role of pro-inflammatory cytokines in triggering pathophysiological changes associated with depression, primarily major depressive disorder (MDD), as well as the possibility of using anti-inflammatory drugs as antidepressants.


Assuntos
Transtorno Depressivo Maior , Preparações Farmacêuticas , Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Citocinas , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos
3.
Medicina (Kaunas) ; 57(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200746

RESUMO

Background and Objectives: Predominant polarity (PP) may be a useful course specifier in at least a significant proportion of patients with Bipolar Disorder (BD), being associated with several clinically relevant correlates. Emerging evidence suggests that the concept of PP might influence the selection of maintenance treatments, based on a drug polarity index (PI) which measures the greater antidepressive vs. antimanic preventive efficacy of mood stabilizers over long-term maintenance treatment. In this study, we aimed to validate the PI in a large sample of Italian BD patients with accurate longitudinal characterization of the clinical course, which ensured a robust definition of the PP. Materials and Methods: Our sample is comprised of 653 patients with BD, divided into groups based on the predominant polarity (manic/hypomanic predominant polarity-MPP, depressive predominant polarity-DPP and no predominant polarity). Subsequently we calculated the mean total polarity index for each group, and we compared the groups. Results: When we examined the mean PI of treatments prescribed to individuals with DPP, MPP and no predominant polarity, calculated using two different methods, we failed to find significant differences, with the exception of the PI calculated with the Popovic method and using the less stringent criterion for predominant polarity (PP50%). Conclusions: Future prospective studies are needed in order to determine whether the predominant polarity is indeed one clinical factor that might guide the clinician in choosing the right mood stabilizer for BD maintenance treatment.


Assuntos
Transtorno Bipolar , Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Humanos , Itália , Estudos Prospectivos
4.
Molecules ; 26(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207264

RESUMO

Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer's disease (AD). Activated MAO induces the amyloid-beta (Aß) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme's physiology may lead to the future advancement of these drugs.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Monoaminoxidase/metabolismo , Animais , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Humanos , Neurotransmissores/metabolismo
5.
Transl Psychiatry ; 11(1): 381, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238923

RESUMO

Major depressive disorder (MDD) is complex and multifactorial, posing a major challenge of tailoring the optimal medication for each patient. Current practice for MDD treatment mainly relies on trial and error, with an estimated 42-53% response rates for antidepressant use. Here, we sought to generate an accurate predictor of response to a panel of antidepressants and optimize treatment selection using a data-driven approach analyzing combinations of genetic, clinical, and demographic factors. We analyzed the response patterns of patients to three antidepressant medications in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, and employed state-of-the-art machine learning (ML) tools to generate a predictive algorithm. To validate our results, we assessed the algorithm's capacity to predict individualized antidepressant responses on a separate set of 530 patients in STAR*D, consisting of 271 patients in a validation set and 259 patients in the final test set. This assessment yielded an average balanced accuracy rate of 72.3% (SD 8.1) and 70.1% (SD 6.8) across the different medications in the validation and test set, respectively (p < 0.01 for all models). To further validate our design scheme, we obtained data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) of patients treated with citalopram, and applied the algorithm's citalopram model. This external validation yielded highly similar results for STAR*D and PGRN-AMPS test sets, with a balanced accuracy of 60.5% and 61.3%, respectively (both p's < 0.01). These findings support the feasibility of using ML algorithms applied to large datasets with genetic, clinical, and demographic features to improve accuracy in antidepressant prescription.


Assuntos
Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Demografia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Humanos , Aprendizado de Máquina , Resultado do Tratamento
6.
Br Dent J ; 231(1): 33-42, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34244646

RESUMO

Introduction Significant changes have taken place in the profile of prescription medicines being taken by the adult UK population over the last decade. The aims of this article are to review the literature to understand the overall trends and underlying factors, and then to compare this with the medication profile of a cohort of adult special care dental (SCD) patients. Materials and method Five hundred patient records were examined and retrospective data on systemic medicines being taken were obtained and classified according to the index used in the British National Formulary (BNF).Results The results revealed a high level of polypharmacy with 57% of SCD patients taking three or more medicines compared to 24% of the population in England. Antiepileptic drugs were the most frequently taken group of medicines (42%), followed by antidepressants (39.7%) and antipsychotics (37.6%). Conclusions Our results demonstrate the medical complexity of patients in this cohort and enable clinicians to increase their familiarity with the most commonly taken medicines and the tools available to manage the implications for dental care.


Assuntos
Antidepressivos , Medicamentos sob Prescrição , Adulto , Antidepressivos/uso terapêutico , Inglaterra , Humanos , Polimedicação , Estudos Retrospectivos
7.
Molecules ; 26(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201675

RESUMO

The complex pathophysiology of depression, together with the limits of currently available antidepressants, has resulted in the continuous quest for alternative therapeutic strategies. Numerous findings suggest that pharmacological blockade of α2-adrenoceptor might be beneficial for the treatment of depressive symptoms by increasing both norepinephrine and serotonin levels in certain brain areas. Moreover, the antidepressant properties of 5-HT7 receptor antagonists have been widely demonstrated in a large set of animal models. Considering the potential therapeutic advantages in targeting both α2-adrenoceptors and 5-HT7 receptors, we designed a small series of arylsulfonamide derivatives of (dihydrobenzofuranoxy)ethyl piperidines as dually active ligands. Following green chemistry principles, the designed compounds were synthesized entirely using a sustainable mechanochemical approach. The identified compound 8 behaved as a potent α2A/5-HT7 receptor antagonist and displayed moderate-to-high selectivity over α1-adrenoceptor subtypes and selected serotonin and dopaminergic receptors. Finally, compound 8 improved performance of mice in the forced swim test, displaying similar potency to the reference drug mirtazapine.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/química , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 2/síntese química , Antagonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Animais , Antidepressivos/uso terapêutico , Escala de Avaliação Comportamental , Depressão/fisiopatologia , Células HEK293 , Humanos , Ligantes , Masculino , Camundongos , Mirtazapina/farmacologia , Mirtazapina/uso terapêutico , Norepinefrina/metabolismo , Piperidinas/química , Ratos , Receptores de Serotonina/genética , Serotonina/metabolismo , Natação
8.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207724

RESUMO

Selective antagonists of thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2), in order to enable a better understanding of this peptide's central functions, have not been identified. Using pGlu-Glu-Pro-NH2 ([Glu2]TRH) as a lead peptide and with modification at its central residue, our studies focused on some of its analogues synthesized as potential functional antagonists of TRH in the rodent brain. Among the peptides studied, the novel isomeric analogue [ß-Glu2]TRH was found to suppress the analeptic and antidepressant-like pharmacological activities of TRH without eliciting intrinsic effects in these paradigms. [ß-Glu2]TRH also completely reversed TRH's stimulation of acetylcholine turnover in the rat hippocampus without a cholinergic activity of its own, which was demonstrated through in vivo microdialysis experiments. Altogether, [ß-Glu2]TRH emerged as the first selective functional antagonist of TRH's prominent cholinergic actions, by which this endogenous peptide elicits a vast array of central effects.


Assuntos
Antidepressivos , Estimulantes do Sistema Nervoso Central , Hipocampo/metabolismo , Peptídeos , Hormônio Liberador de Tireotropina/antagonistas & inibidores , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/farmacologia , Hipocampo/patologia , Masculino , Camundongos , Peptídeos/química , Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Hormônio Liberador de Tireotropina/metabolismo
9.
Medicine (Baltimore) ; 100(28): e26411, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260525

RESUMO

BACKGROUND: Antidepressant drugs are mainly used to treat depression clinically. ABCB1 affects the P-glycoprotein activity and changes the amount of drugs in the blood tissue barrier that can be squeezed back into the blood, thus affecting the efficacy of antidepressants. In this present study, Meta-analysis was performed to further investigate the influences of ABCB1 gene polymorphism on antidepressant response. METHODS: Relevant literatures were searched from the PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc, and Wan Fang databases up to May 2021 without any language restrictions. STATA 16.0 software was applied for this meta-analysis. Odds ratio (OR) and its corresponding 95% confidence interval (CI) were calculated. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will summarize the effects of ABCB1 gene polymorphism on antidepressant response.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Antidepressivos/farmacocinética , Humanos , Razão de Chances , Projetos de Pesquisa
10.
Trials ; 22(1): 504, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321056

RESUMO

BACKGROUND: Post-stroke depression (PSD) is a common complication after stroke which hinders functional recovery and return to social participation of stroke patients. Efficacy of conventional drug therapies for patients with PSD is still uncertain. Therefore, many patients prefer to use complementary and alternative therapies for PSD. Tuina (traditional Chinese manual manipulation) with herbal ointment is an integration of manual therapy, and ointment is an important part of traditional Chinese medicine (TCM) therapy. Preliminary experiments have shown that the Tuina with herbal ointment can improve the mental state of patients with PSD. The purpose of this study is to observe and verify the efficacy of Tuina combined with herbal ointment for patients with post-stroke depression, and to lay a foundation for further research on its mechanism of action. METHODS/DESIGN: In this study, a randomized controlled trial will be conducted in parallel, including two intervention groups: Tuina with herbal ointment group and herbal ointment for control group. A total of 84 eligible participants will be randomly assigned to the groups in a 1:1 ratio. All participants will receive conventional antidepressant venlafaxine treatment (75 mg QD), on which they received two different interventions. The interventions for both groups will be carried out 5 times each week for a period of 2 weeks. The primary outcome will be the Hamilton Rating Scale for Depression (HAMD). Secondary outcomes will include transcranial magnetic stimulation (TMS), as well as 36-item Short-Form Health Survey (SF-36) and Treatment Emergent Symptom Scale (TESS). They will be assessed at the baseline, at the end of the intervention (2 weeks), and during the 1 month and 3 months of follow-up by repeated measures analysis of variance. The significance level is 5%. Adverse events will be monitored at each visit to assess safety. All outcomes will be assessed and analyzed by researchers blinded to the treatment allocation. The purpose of this study will focus on observing the efficacy of Tuina with herbal ointment for patients with post-stroke depression, and to explore further the mechanisms of its effects. DISCUSSION: This study may evaluate clinical application value and safety of Tuina with herbal ointment in PSD patients, which can provide basis for clinical research and mechanism exploration of PSD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033887 . Registered on 15 June 2020. DISSEMINATION: The results will be published in peer-reviewed journals and disseminated through the study's website and conferences.


Assuntos
Depressão , Acidente Vascular Cerebral , Antidepressivos , Depressão/diagnóstico , Depressão/tratamento farmacológico , Depressão/etiologia , Humanos , Medicina Tradicional Chinesa , Pomadas , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Resultado do Tratamento
11.
Int J Mol Sci ; 22(14)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34299040

RESUMO

Late-life depression (LLD), compared to depression at a young age, is more likely to have poor prognosis and high risk of progression to dementia. A recent systemic review and meta-analysis of the present antidepressants for LLD showed that the treatment response rate was 48% and the remission rate was only 33.7%, thus implying the need to improve the treatment with other approaches in the future. Recently, agents modulating the glutamatergic system have been tested for mental disorders such as schizophrenia, dementia, and depressive disorder. Ketamine, a noncompetitive NMDA receptor (NMDAR) antagonist, requires more evidence from randomized clinical trials (RCTs) to prove its efficacy and safety in treating LLD. The metabotropic receptors (mGluRs) of the glutamatergic system are family G-protein-coupled receptors, and inhibition of the Group II mGluRs subtypes (mGlu2 and mGlu3) was found to be as effective as ketamine in exerting rapid antidepressant activity in some animal studies. Inflammation has been thought to contribute to depression for a long time. The cytokine levels not only increase with age but also decrease serotonin. Regarding LLD, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) released in vivo are likely to contribute to the reduced serotonin level. Brain-derived neurotrophic factor (BDNF), a growth factor and a modulator in the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors, probably declines quantitatively with age. Recent studies suggest that BDNF/TrkB decrement may contribute to learning deficits and memory impairment. In the process of aging, physiological changes in combination with geriatric diseases such as vascular diseases result in poorer prognosis of LLD in comparison with that of young-age depression. Treatments with present antidepressants have been generally unsatisfactory. Novel treatments such as anti-inflammatory agents or NMDAR agonists/antagonists require more studies in LLD. Last but not least, LLD and dementia, which share common pathways and interrelate reciprocally, are a great concern. If it is possible to enhance the treatment of LDD, dementia can be prevented or delated.


Assuntos
Envelhecimento/efeitos dos fármacos , Antidepressivos/farmacologia , Demência/patologia , Depressão/fisiopatologia , Animais , Demência/epidemiologia , Depressão/tratamento farmacológico , Humanos
12.
J Agric Food Chem ; 69(25): 7016-7027, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34060828

RESUMO

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha (kucha), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis. This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.


Assuntos
Alcaloides , Camellia sinensis , Animais , Antidepressivos , Fator Neurotrófico Derivado do Encéfalo/genética , China , Depressão/tratamento farmacológico , Hipocampo , Camundongos , Neurogênese , Purinas , Ratos , Estresse Psicológico , Chá , Ácido Úrico/análogos & derivados
13.
Psychiatr Danub ; 33(2): 147-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185734

RESUMO

Depression is the most prevalent mood disorder among pregnant women. Only 50% of women seek intervention during gestation. Untreated during pregnancy, depression can induce obstetric and neonatal complications, most commonly, anhedonia, suboptimal weight gain, suicidal behavior, pre-term birth, and/or spontaneous miscarriage. The babies more often suffer cognitive deficits, low birth weight, and growth delay. The mothers subsequently also experience an increased risk for significant degrees of postpartum depression. Those with relatively milder cases of depression should initially receive psychotherapy. Otherwise, there are many antidepressant medications available for the pharmacotherapy of depression. However, treating pregnant females with depression is a challenge because of potential teratogenic effects caused by many pharmaceuticals. Physicians should know the recommended guidelines for treating depressed women during a time of gestation. It is crucial to identify women suffering from depression during pregnancy, and electing those that warrant pharmacotherapy while picking the best and safest medication is a complex process with paramount significance. Before prescribing an antidepressant drug, explain the advantages and disadvantages of the interventions. Whenever prescribing during these circumstances, more than conventionally close obstetric, emotional, and medication monitoring is to be provided. This would also include an emphasis on diet, exercise, psychotherapy, and avoidance of any non-critical medicinal or other substance exposures.


Assuntos
Depressão Pós-Parto , Complicações na Gravidez , Antidepressivos/efeitos adversos , Exercício Físico , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Gestantes
14.
Phytomedicine ; 87: 153581, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091149

RESUMO

BACKGROUND: Xiaoyaosan (XYS), a classic traditional Chinese medicine (TCM) prescription that contained eight Chinese herbs, has been used for treating depression for thousands of years. Yet, the underlying mechanisms are still unclear, which need to be investigated from various perspectives. Disassembling a prescription is one of the effective approaches to study the effects and the mechanisms of TCM prescriptions. By disassembling the prescription, we can find effective combinations of individual herbs to simplify the scale of a given prescription. Accordingly, herein, XYS was disassembled into Shugan and Jianpi groups. PURPOSE: This study aimed to explore the anti-depressive effects of XYS and its disassembled groups on the digestive system functions and the cecal microbiota of rats. METHODS: XYS was divided into two efficacy groups, i.e., the Shugan (SG) and the Jianpi (JP) groups. A depression model was applied by using the chronic unpredictable mild stress (CUMS) method. Various classic behavioral tests were performed to assess the anti-depressive effects of the XYS, the SG, and the JP. Afterward, the effects of the three groups on the digestive system functions and the cecum microbiota of depression rats were evaluated. On top of this, correlation analyses between behavioral and digestive system function indexes and cecum microbiota were conducted. RESULTS: The XYS, the SG, and the JP had significant callback effects on depressive behaviors and gastrointestinal dysfunctions of CUMS rats. The compositions of the gut bacterial community were variable among the five groups. The community composition of the SG was the most similar to that of NC, followed by the XYS and the JP. At phylum, family, and genus levels, 31 potential microbial biomarkers associated with CUMS were identified. Twenty biomarkers were significantly reversed by the SG while 16 and 11 biomarkers were reversed by the XYS and the JP, respectively. The results of degrees of regulatory effects showed that the SG had the highest efficacy index (EI) than the XYS and the JP. CONCLUSION: Regarding the regulation of cecal microbiota of depression rats, the SG treatment was better than XYS and JP. Therefore, SG could be used individually for the clinical treatment of depression, especially in patients with gastrointestinal and gut microbiota disorders.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Depressão/microbiologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/análise , Medicamentos de Ervas Chinesas/química , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Esvaziamento Gástrico/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Masculino , Ratos Sprague-Dawley , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/microbiologia
15.
Syst Rev ; 10(1): 171, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108032

RESUMO

BACKGROUND: Major depression significantly impairs quality of life, increases the risk of suicide, and poses tremendous economic burden on individuals and societies. Duloxetine, a serotonin norepinephrine reuptake inhibitor, is a widely prescribed antidepressant. The effects of duloxetine have, however, not been sufficiently assessed in earlier systematic reviews and meta-analyses. METHODS/DESIGN: A systematic review will be performed including randomised clinical trials comparing duloxetine with 'active' placebo, placebo or no intervention for adults with major depressive disorder. Bias domains will be assessed, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed. We will conduct meta-analyses. Trial sequential analysis will be conducted to control random errors, and the certainty of the evidence will be assessed using GRADE. To identify relevant trials, we will search Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, PsycINFO, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index-Science and Conference Proceedings Citation Index-Social Science & Humanities. We will also search Chinese databases and Google Scholar. We will search all databases from their inception to the present. Two review authors will independently extract data and perform risk of bias assessment. Primary outcomes will be the difference in mean depression scores on Hamilton Depression Rating Scale between the intervention and control groups and serious adverse events. Secondary outcomes will be suicide, suicide-attempts, suicidal ideation, quality of life and non-serious adverse events. DISCUSSION: No former systematic review has systematically assessed the beneficial and harmful effects of duloxetine taking into account both the risks of random errors and the risks of systematic errors. Our review will help clinicians weigh the benefits of prescribing duloxetine against its adverse effects and make informed decisions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2016 CRD42016053931.


Assuntos
Transtorno Depressivo Maior , Adulto , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina/uso terapêutico , Humanos , Metanálise como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ideação Suicida , Revisões Sistemáticas como Assunto
16.
Phytomedicine ; 88: 153598, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34111615

RESUMO

INTRODUCTION: Depression is one of the leading causes of death worldwide. Lower antioxidant concentrations and increased oxidative stress levels contribute to the development of depression. Effective and tolerable medications are urgently needed. Nrf2 and PRDX2 are promising targets in the treatment of oxidative stress and, therefore, promising for the development of novel antidepressants. Ursolic acid (UA), a natural triterpenoid found in various plants is known to exert neuroprotective and antioxidant effects. Skn-1 (which corresponds to human Nrf2) and prdx2 deficient mutants of the nematode Caenorhabditis elegans are suitable models to study the effect of UA on these targets. Additionally, stress assays are used to mimic stress or depressed state. METHODS: We examined the antioxidant activity of UA in Caenorhabditis elegans wildtype and skn-1- and prdx2-deficient strains by H2DCF-DA and juglone assays as well as osmotic and heat stress assays. Additionally, we analyzed the binding of UA to human PRDX2 and Skn-1 proteins by molecular docking and microscale thermophoresis. RESULTS: UA exerted strong antioxidant activities. Additionally, induction of stress resistance towards osmotic and heat stress was observed. qRT-PCR revealed that UA upregulated the gene expression of skn-1 and prdx2. Molecular docking studies supported these findings. CONCLUSION: Our findings implicate that the strong antioxidant activity of UA may exert anti-depressive effects by its interaction with the Skn-1 transcription factor, which is part of a detoxification network, and the antioxidant PRDX2 protein, which protects the organism from the detrimental effects of radical oxygen species.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Depressão/genética , Estresse Fisiológico/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Antidepressivos/farmacologia , Antioxidantes/farmacologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mutação , Estresse Oxidativo/efeitos dos fármacos , Peroxirredoxinas/genética , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Triterpenos/química
17.
Phytomedicine ; 88: 153606, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34111616

RESUMO

BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear. PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms. METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored. RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling. CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Depressão/patologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Antidepressivos/farmacologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Comorbidade , Depressão/tratamento farmacológico , Depressão/epidemiologia , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Transl Psychiatry ; 11(1): 347, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34091594

RESUMO

Electroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10-8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10-7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Sídák's p = 0.0031) and 20 (Sídák's p = 4.2 × 10-5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.


Assuntos
Eletroconvulsoterapia , Antidepressivos/uso terapêutico , Epigenoma , Humanos , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
19.
Transl Psychiatry ; 11(1): 354, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103475

RESUMO

A combination of different risk factors, such as genetic, environmental and psychological factors, together with immune system, stress response, brain neuroplasticity and the regulation of neurotransmitters, is thought to lead to the development of major depressive disorder (MDD). A growing number of studies have tried to investigate the underlying mechanisms of MDD by analysing the expression levels of genes involved in such biological processes. These studies have shown that MDD is not just a brain disorder, but also a body disorder, and this is mainly due to the interplay between the periphery and the Central Nervous System (CNS). To this purpose, most of the studies conducted so far have mainly dedicated to the analysis of the gene expression levels using postmortem brain tissue as well as peripheral blood samples of MDD patients. In this paper, we reviewed the current literature on candidate gene expression alterations and the few existing transcriptomics studies in MDD focusing on inflammation, neuroplasticity, neurotransmitters and stress-related genes. Moreover, we focused our attention on studies, which have investigated mRNA levels as biomarkers to predict therapy outcomes. This is important as many patients do not respond to antidepressant medication or could experience adverse side effects, leading to the interruption of treatment. Unfortunately, the right choice of antidepressant for each individual still remains largely a matter of taking an educated guess.


Assuntos
Fenômenos Biológicos , Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Biomarcadores , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Humanos
20.
Nutrients ; 13(5)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068669

RESUMO

Probiotic bacteria are widely accepted as therapeutic agents against inflammatory bowel diseases for their immunostimulating effects. In the last decade, more evidence has emerged supporting the positive effects of probiotics on the course of neurodegenerative and psychiatric diseases. This brief review summarizes the data from clinical studies of probiotics possessing antidepressant properties and focuses on the potential genes and proteins underlying these mechanisms. Data from small-sample placebo-controlled pilot studies indicate that certain strains of bacteria can significantly reduce the symptoms of depression, especially in depressed patients. Despite the disparity between studies attempting to pinpoint the bacterial putative genes and proteins accounting for these mechanisms, they ultimately show that bacteria are a potential source of metabiotics-microbial metabolites or structural components. Since the constituents of cells-namely, secreted proteins, peptides and cell wall components-are most likely to be entangled in the gut-brain axis, they can serve as starting point in the search for probiotics with concrete properties.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Microbioma Gastrointestinal/fisiologia , Probióticos/uso terapêutico , Bactérias/genética , Bactérias/metabolismo , Encéfalo , Humanos , Doenças Inflamatórias Intestinais
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