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1.
Expert Opin Drug Metab Toxicol ; 16(1): 31-44, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31795773

RESUMO

Introduction: This is a review of the drug interactions (DIs) between newer antidepressants and oral anticoagulants (OACs): vitamin K antagonists (VKAs) and direct-acting OACs (DOACs).Areas covered: Articles were obtained from PubMed searches performed for each of the newer antidepressants and oral anticoagulants. The basic pharmacokinetic and pharmacodynamic mechanisms for DIs with these drugs were summarized. Some newer antidepressants are inhibitors of a number of cytochrome P450 (CYP) isoforms and many antidepressants appear to have potential to impair serotonin platelet function and increase bleeding risk.Expert opinion: Clinicians should not forget that the DIs between newer antidepressants and VKAs can be potentially lethal. Among SSRIs, fluoxetine and fluvoxamine appear to be associated with the highest DI risk with warfarin, the most commonly prescribed VKA worldwide. Case reports featuring duloxetine, mirtazapine and trazadone suggested potential for interaction with warfarin. As CYP3A4 is an important metabolic pathway for all DOACs except dabigatran, it appears reasonable to recommend avoiding the co-prescription of fluoxetine and fluvoxamine (weak to moderate CYP3A4 inhibitors) and St John's wort (CYP3A4 inducer). Many package inserts for the newer antidepressants include a warning regarding an increased risk of bleeding events with concomitant use of these agents with OACs.


Assuntos
Anticoagulantes/administração & dosagem , Antidepressivos/administração & dosagem , Interações de Medicamentos , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Antidepressivos/efeitos adversos , Antidepressivos/farmacologia , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Inibidores das Enzimas do Citocromo P-450/farmacologia , Hemorragia/induzido quimicamente , Humanos , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Varfarina/farmacocinética
2.
Epidemiol Psychiatr Sci ; 29: e79, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841104

RESUMO

In March 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression in adults. Esketamine is the S-enantiomer of ketamine, an FDA-approved anaesthetic, known to cause dissociation and, occasionally, hallucinations. While ketamine has not been approved for depression in the USA or in any other country, it has been used off-label in cases of severe depression. This commentary critically reviewed the evidence on esketamine submitted to the FDA, aiming to draw implications for clinical practice, research and regulatory science.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Depressão/diagnóstico , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Aprovação de Drogas , Medicina Baseada em Evidências , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Estados Unidos , United States Food and Drug Administration
4.
J Microbiol Biotechnol ; 29(9): 1369-1374, 2019 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-31564078

RESUMO

We isolated Lactobacillus mucosae NK41 and Bifidobacterium longum NK46 from human feces, which induced BDNF expression in corticosterone-stimulated SH-SY5Y cells, and examined their anti-depressive effects in mice. NK41, NK46, and their (1:1) mixture significantly mitigated immobilization stress (IS)-induced anxiety-like/depressive behaviors, hippocampal NF-κB activation, BDNF expression, Iba1+ cell population, and blood corticosterone, TNF-α, IL- 6, and lipopolysaccharide levels. Furthermore, they inhibited colitis marker NF-κB activation, and TNF-α expression in mice with IS-induced anxiety/depression. They additionally suppressed gut Proteobacteria and Bacteroidetes populations and bacterial lipopolysaccharide production. These findings suggest that NK41 and NK46 may alleviate anxiety/depression and colitis by suppressing gut dysbiosis.


Assuntos
Ansiedade/dietoterapia , Bifidobacterium longum , Depressão/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus , Probióticos/farmacologia , Probióticos/uso terapêutico , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ansiedade/sangue , Ansiedade/microbiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Colite/microbiologia , Colite/patologia , Corticosterona/sangue , Depressão/sangue , Depressão/microbiologia , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/patologia , Fezes/microbiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Interleucina-6/sangue , Lipopolissacarídeos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , NF-kappa B/metabolismo , Probióticos/administração & dosagem , Estresse Psicológico/sangue , Estresse Psicológico/microbiologia , Estresse Psicológico/psicologia , Fator de Necrose Tumoral alfa/sangue
5.
Expert Opin Drug Metab Toxicol ; 15(10): 831-847, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31526279

RESUMO

Introduction: Nowadays, the first-line medications in depression include SSRIs, SNRIs, NDRIs, NaSSAs, SMSs, or a melatonin (M1/M2) receptor agonist and a 5-HT2C receptor antagonist. These drugs have quite similar antidepressant efficacy and safety profiles, but they differ in chemical structure, receptor affinity, and pharmacokinetics. Areas covered: Pharmacokinetic properties of first-line antidepressant drugs and factors influencing their pharmacokinetic processes are presented. Alterations in pharmacokinetics of newer antidepressants in special populations are summarized. In addition, the significance of therapeutic drug monitoring (TDM) and pharmacogenetic testing in dose optimization for the treatment of depressive disorders using newer antidepressants is discussed. Expert opinion: Due to the fact that 30-40% of depressive patients do not respond to the therapy and that the incidence of depression is constantly growing, the search for new more effective and safer antidepressant therapies is becoming an urgent need. More well-designed clinical studies under naturalistic conditions are needed to establish/refine therapeutic ranges for older and current state-of-the-art antidepressant drugs. The pharmacogenetic testing with concomitant application of TDM seems to be the best way for implementing personalized dosing of current state-of-the-art antidepressants metabolized by polymorphic CYPs, especially when co-administered with strong inhibitors or other substrates of CYP2D6 or CYP2C19.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Animais , Antidepressivos/farmacocinética , Antidepressivos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Humanos , Farmacogenética
6.
Psychiatr Danub ; 31(Suppl 3): 585-590, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488795

RESUMO

Ketamine is an anaesthetic and analgesic agent that demonstrates the antidepressive effect in major depression. Several administrations routes, dosing schemas and esketamine are investigated in basic and clinical research with particular focus on treatment-resistant depression (TRD) where drug demonstrates its efficacy where very limited alternatives are available. The majority of ketamine studies in TRD treatment reported no serious adverse events regardless the administration route or regimen. However, the most commonly observed adverse events following ketamine administration in antidepressive doses include general, psychotomimetic, dissociative and hemodynamic ones. The side effects are mild or moderate, well-tolerated and transient. This paper discusses the risks regarding cardiovascular safety in MDD patients in short-term ketamine administration with particular focus on the effect on blood pressure and adverse drug reactions mitigation measures. The increase in systolic (SBP) and diastolic (DBP) blood pressure is dose-dependent and begins shortly after administration peaking at around 30 to 50 minutes with SBP and DBP rise from 10% to 50% above predose values and resolving at approximately 2 to 4 hours after the dose administration. These changes generally are primarily asymptomatic. The elevations in SBP and DBP are observed on each dosing day with multiple administration schema. The treatment with ketamine and esketamine is contradicted in subjects at risk of an increase in blood pressure or intracranial pressure. The current evidence indicates the blood pressure should be assessed prior to dosing with ketamine and hypertensive individuals shall receive effective lifestyle/pharmacologic management prior to treatment. Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains elevated acute blood pressure management shall be delivered. In patients experiencing symptoms of hypertensive crisis immediate emergency care must be provided. The unmet need for improved pharmacotherapies for TRD means the use of ketamine and esketamine is warranted therapeutic option in patients who fail to achieve a sustained remission of depressive symptoms with drugs with monoamine-based mechanisms of action. Adequate safety measures must be applied when using ketamine/esketamine in TRD subjects with particular focus on somatic comorbidities as the transient drug effect on cardiovascular system is demonstrated and of clinical significance.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Depressão/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
7.
BMC Complement Altern Med ; 19(1): 215, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412844

RESUMO

BACKGROUND: Mounting evidence indicates that the cerebral cortex is an important physiological system of emotional activity, and its dysfunction may be the main cause of stress. Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS), which initiates rapid signal transmission in the synapse before its reuptake into the surrounding glia, specifically astrocytes (ASTs). The astrocytic excitatory amino acid transporters 1 (EAAT1) and 2 (EAAT2) are the major transporters that take up synaptic glutamate to maintain optimal extracellular glutamic levels, thus preventing accumulation in the synaptic cleft and ensuing excitotoxicity. Growing evidence has shown that excitotoxicity is associated with depression. Therefore, we hypothesized that the underlying antidepressant-like mechanism of Xiaoyaosan (XYS), a Chinese herbal formula, may be related to the regulation of astrocytic EAATs. Therefore, we studied the antidepressant mechanism of XYS on the basis of EAAT dysfunction in ASTs. METHODS: Eighty adult C57BL/6 J mice were randomly divided into 4 groups: a control group, a chronic unpredictable mild stress (CUMS) group, a Xiaoyaosan (XYS) treatment group and a fluoxetine hydrochloride (Flu) treatment group. Except for the control group, mice in the other groups all received chronic unpredictable mild stress for 21 days. Mice in the control and CUMS groups received gavage administration with 0.5 mL of normal saline (NS) for 21 days, and mice in the XYS and Flu treatment groups were administered dosages of 0.25 g/kg/d and 2.6 mg/kg/d by gavage. The effects of XYS on the depressive-like behavioral tests, including the open field test (OFT), forced swimming test (FST) and sucrose preference test (SPT), were examined. The glutamate (Glu) concentrations of the prefrontal cortex (PFC) were detected with colorimetry. The morphology of neurons in the PFC was observed by Nissl staining. The expression of glial fibrillary acidic protein (GFAP), NeuN, EAAT1 and EAAT2 proteins in the PFC of mice was detected by using Western blotting and immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of the GFAP, NeuN, EAAT1 and EAAT2 genes in the PFC of mice. RESULTS: The results of behavioral tests showed that CUMS-induced mice exhibited depressive-like behavior, which could be improved in some tests with XYS and Flu treatment. Immunohistochemistry and Western blot analysis showed that the protein levels of GFAP, NeuN, EAAT1 and EAAT2 in the PFC of CUMS mice were significantly lower than those in the control group, and these changes could be reversed by XYS and Flu. The results of qPCR analysis showed that the expression of GFAP, NeuN, EAAT1 and EAAT2 mRNAs in the PFC of CUMS mice was not significantly changed, with the exception of EAAT2, compared with that of the control group, while the expression of the above mRNAs was significantly higher in the XYS and Flu groups than that in the CUMS group. CONCLUSION: XYS may exert antidepressant-like effects by improving the functions of AST and EAATs and attenuating glutamate-induced neuronal damage in the frontal cortex.


Assuntos
Antidepressivos/administração & dosagem , Astrócitos/efeitos dos fármacos , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Córtex Pré-Frontal/citologia , Animais , Comportamento Animal , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Transportador 1 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/genética , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos
8.
Indian J Med Res ; 149(4): 497-502, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411173

RESUMO

Background & objectives: Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD), but biomarkers to assess oxidative stress in patients with MDD have yielded ambiguous results. Glutathionyl haemoglobin (GS-Hb) has been reported as a stable and potential biomarker for oxidative stress in various clinical conditions. The objective of the study was to evaluate GS-Hb as a potential biomarker of oxidative stress in patients with MDD through its quantification and to compare the levels of GS-Hb in age- and gender-matched healthy controls. Methods: The levels of GS-Hb were estimated using liquid chromatography coupled to electrospray ionization mass spectrometry in patients diagnosed with MDD and in a subset of patients after six weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Results: GS-Hb levels in drug-naïve patients with MDD (n=26) were significantly elevated compared to matched healthy controls (n=17). GS-Hb levels were not significantly different between MDD patients with and without co-morbid anxiety disorders. There were no significant differences in GS-Hb levels following six weeks of treatment with SSRIs compared to baseline. Interpretation & conclusions: Compared to controls, GS-Hb level in patients with MDD was significantly elevated, suggestive of increased oxidative stress associated with MDD. However, six weeks of antidepressant treatment was not sufficient to modify the alterations in antioxidant/oxidant system. Further studies need to be done with a large sample of MDD patients with a longer duration of antidepressant treatment.


Assuntos
Biomarcadores/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Glutationa/sangue , Adulto , Antidepressivos/administração & dosagem , Cromatografia Líquida , Transtorno Depressivo Maior/patologia , Feminino , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Inibidores de Captação de Serotonina/administração & dosagem , Espectrometria de Massas por Ionização por Electrospray
9.
J Clin Psychopharmacol ; 39(5): 479-484, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425466

RESUMO

PURPOSE: This review examined the current literature about the potential relationship between the use of antidepressants during pregnancy and neonatal seizures. METHODS: PubMed was searched for English language reports published between January 1, 1996, and October 31, 2018, by using combinations of the following key words: pregnancy, neonatal outcome, neonatal convulsion, neonatal seizure, SSRI, selective serotonin norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), antidepressants, sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, duloxetine, bupropion, amitriptyline, imipramine, and clomipramine. FINDINGS: A total of 9 relevant studies that met the review criteria were examined. The prevalence rates of neonatal seizures in the antidepressant groups and control groups were 0.30% to 0.91% and 0.10% to 0.30%, respectively. The use of selective serotonin reuptake inhibitors was associated with up to 5-fold increase in the risk of neonatal seizures. Compared with the controls, higher risks were reported in newborns of pregnant women using any antidepressant or tricyclic antidepressants albeit in a limited number of studies. Exposure to antidepressants in the third trimester of pregnancy appeared to be associated more with neonatal seizures compared with earlier exposure. IMPLICATONS: Although an increased risk of neonatal seizures in newborns antenatally exposed to antidepressants especially selective serotonin reuptake inhibitors may be suggested, the available studies have severe methodological limitations to enable any firm conclusion.


Assuntos
Antidepressivos/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Convulsões/epidemiologia , Antidepressivos/efeitos adversos , Feminino , Humanos , Recém-Nascido , Gravidez , Trimestres da Gravidez , Prevalência , Convulsões/etiologia
10.
Clin Drug Investig ; 39(11): 1077-1092, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31399894

RESUMO

BACKGROUND AND OBJECTIVES: In Japan, polypharmacy reduction policy, which reduces the reimbursement of medical cost, was introduced to address unnecessary psychotropic polypharmacy. The rule was applied to the prescriptions of three or more anxiolytics or three or more hypnotics in the policy introduced in 2012. The prescriptions of four or more antidepressants or four or more antipsychotics were added to the rule in the policy revised in 2014. Furthermore, the prescriptions of three or more drugs of anxiolytics, hypnotics, antidepressants, or antipsychotics were subject to the reduction criteria of the policy revision in 2016. Benzodiazepine receptor agonists (BZs) are classified both into anxiolytics and hypnotics, and the reduction rule was not applied to the category of BZs before April 2018. This study aimed to examine the effect of the policy on the prescriptions of four drug categories as well as BZs from the point of view of the number of drugs and doses. METHODS: This was a retrospective observational study using a large-scale Japanese health insurance claims database. Patients who were prescribed at least one psychotropic drug (anxiolytic, hypnotic, antidepressant, or antipsychotic) during the study period (from April 2011 to March 2017) were selected. Segmented regression analysis was used to analyze the proportions of patients with three or more or four or more drugs as well as patients above clinically recommended doses, and the means of the average daily doses by drug category. RESULTS: A total of 312,167 patients were identified as a study population. The proportions of patients with three or more drugs in anxiolytics, hypnotics, antidepressants, and antipsychotics significantly decreased after the introduction or revisions of the policy, but not BZs. The proportions of patients with three or more drugs in March 2017 were 0.9%, 2.0%, 1.2%, 2.4%, and 8.9% in anxiolytics, hypnotics, antidepressants, antipsychotics, and BZs, respectively. The effect of the policy in reducing the proportions of patients above clinically recommended doses was identified in antipsychotics after the revision in 2016, but not identified in the sum of anxiolytics and hypnotics as well as BZs after the revision in 2014, and antidepressants after the revision in 2016. The proportions of monotherapy were increased from April 2011 to March 2017 only for antidepressants (76.9% → 80.8%) and antipsychotics (79.8% → 82.1%), and not changed or decreased for anxiolytics (85.2% → 85.7%), hypnotics (78.6% → 77.6%), sum of anxiolytics and hypnotics (68.1% → 65.7%), BZs (68.0% → 67.3%), and sum of psychotropic drugs (52.1% → 49.9%). CONCLUSIONS: The polypharmacy reduction policy reduced the proportions of patients with three or more drugs in four drug categories, but not BZs. Only limited effects were seen for reducing the proportions of patients above clinically recommended doses. The policy was revised in April 2018 again. Further investigation is needed to examine the effect of the revision in 2018.


Assuntos
Bases de Dados Factuais/tendências , Prescrições de Medicamentos , Revisão da Utilização de Seguros/tendências , Polimedicação , Psicotrópicos/administração & dosagem , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Bases de Dados Factuais/normas , Prescrições de Medicamentos/normas , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Revisão da Utilização de Seguros/normas , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Behav Ther ; 50(5): 851-863, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31422843

RESUMO

The majority of people with depression in the United States either never seek treatment or gravitate exclusively to antidepressant medication (ADM), despite the existence of other effective treatments, such as cognitive-behavioral therapy (CBT). Reluctance to use psychotherapy is partly due to lack of appropriate mental health literacy and perceptions of low treatment acceptability (appropriateness for a given problem) and credibility (treatment logicalness, and whether the patient expects improvement). In the current investigation, we examined whether providing psychoeducation about CBT for depression would change participant perceptions of the treatment's acceptability and credibility. We recruited 554 (female n = 314; 57%) participants across two online studies, and assessed their baseline perceptions of CBT and ADM using modified Treatment Acceptability (TAAS) and Treatment Credibility and Expectancy (CEQ) scales. Participants were subsequently presented with evidence-based, expert-vetted psychoeducational materials describing CBT and ADM, and were asked to recomplete the TAAS and CEQ. In Study 1, participants endorsed significantly higher CBT-CEQ (credibility/expectancy) scores postpsychoeducation. In Study 2, participants endorsed significantly lower CBT-TAAS (acceptability), and among those with no exposure to depression treatments, endorsed significantly higher CBT-CEQ scores postpsychoeducation. In both studies, there were no perceptual changes of ADM after the psychoeducation. Finally, in Study 2, endorsement of a biological model of depression and depressive symptoms were negatively predictive of CBT's acceptability and credibility and expectancy postpsychoeducation. Perceptions of credibility and expectancy of CBT for depression appear malleable even after exposure to brief psychoeducation, whereas shifting perceptions of CBT's acceptability may require more extensive intervention.


Assuntos
Antidepressivos/administração & dosagem , Terapia Cognitivo-Comportamental/métodos , Adulto , Cognição , Depressão/terapia , Transtorno Depressivo/psicologia , Transtorno Depressivo/terapia , Feminino , Humanos , Masculino , Psicoterapia/métodos , Resultado do Tratamento
12.
Medicine (Baltimore) ; 98(35): e16854, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464912

RESUMO

INTRODUCTION: Major depressive disorder (MDD) is a common condition worldwide, and leads to degradation in quality of life and large socioeconomic costs. There has been increasing demand for new therapies with fewer side effects. SOCG (SOCG tablet) is a modified prescription of So-ochim-tang, which is widely used in Traditional Korean Medicine to treat MDD. We aim to evaluate the efficacy of SOCG in treating MDD, and identify the optimum dose. DESIGN: The protocol we are following is that of a Phase II clinical trial with a randomized, double blinded, placebo controlled, and parallel design. One hundred forty-eight participants will be randomly divided into 4 groups and treated for 8 weeks. OUTCOME MEASURES: The primary outcome will be the score in the Korean Version of the Hamilton Depression Rating Scale. Scores in the Korean version of the Beck Depression Inventory-II Korean Symptom Check List-95 (KSCL-95), State Trait Anxiety Inventory-Korean version, State- Trait Anger Expression Inventory- Korean version (STAXI-K), Insomnia Severity Index (ISI), and the EuroQol-5 Dimension (EQ-5D) will be considered as secondary outcomes. DISCUSSION AND CONCLUSIONS: Demonstration of human safety and efficacy of SOCG in the present trial and identification of the appropriate dose will justify a New Drug Application and a phase III clinical trial. Further, we expect that this new antidepressant will be able to increase cure rates, and alleviate the burden of medical expenses. TRIAL REGISTRATION NUMBER: Clinical Research Information Service, Republic of Korea (KCT0002763).


Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Administração Oral , Adulto , Antidepressivos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Medicina Tradicional Coreana , Pessoa de Meia-Idade , Cooperação do Paciente , Extratos Vegetais/efeitos adversos , Qualidade de Vida , Projetos de Pesquisa , Comprimidos , Resultado do Tratamento , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-31352203

RESUMO

Cistanche tubulosa, one species of Cistanches Herba, was recently confirmed to have antidepressant efficacy in chronic unpredictable stress (CUS) rats by restoring homeostasis of intestinal microbiota. In this paper, we aim to explore the metabolic profile of C. tubulosa in normal and CUS induced depressive model rats in vitro and in vivo. Using UPLC-Q-TOF-MS, the in vitro gastrointestinal metabolism of Cistanche tubulosa extract (CTE) was evaluated in both normal and CUS rats. At the same time, in vivo metabolism of CTE in normal and depressed rats were also investigated in rat urine and feces. A total of 20 and 26 metabolites were characterized from in vitro and in vivo metabolism in normal and CUS rats, respectively. CTE was metabolized to aglycones and degradation products of phenylethanoid glycosides (PhGs) and iridoid glycosides whether by normal or depressed rat intestinal microbiota in vitro. Phase II metabolites of aglycones and degradation products of PhGs and iridoid glycosides were the main metabolites in rat urine and feces. Additionally, the metabolic capability to generate secondary glycosides and aglycones in depressive rat intestinal microbiota was much weaker than that in normal rat intestinal microbiota, which was attributed to the disordered glycoside hydrolases produced by intestinal microbiota in CUS depressed rats. The results of this study laid the foundation for understanding the metabolic process and therapeutic mechanism of CTE's antidepressant property.


Assuntos
Antidepressivos/metabolismo , Cistanche/química , Depressão/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Extratos Vegetais/metabolismo , Animais , Antidepressivos/administração & dosagem , Cistanche/metabolismo , Depressão/tratamento farmacológico , Depressão/psicologia , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Masculino , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estresse Psicológico
14.
Eur J Gen Pract ; 25(3): 157-163, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335225

RESUMO

Background: Comorbid anxiety and depression and type two diabetes mellitus (T2DM) are commonly managed by General Practitioners (GPs). Objectives: To investigate the proportion of people with T2DM who are prescribed either antidepressant or benzodiazepine medications in general practice; to compare people with T2DM that have a prescription with those that do not in terms of patient characteristics, glycaemic control and healthcare utilization. Methods: Anonymized data was collected by GPs and senior medical students from electronic medical records of patients with T2DM in 34 Irish general practices affiliated with the University of Limerick Graduate Entry Medical School during the 2013/14 academic year. Data included demographics, healthcare utilization, prescriptions and most recent glycosylated haemoglobin (HbA1c) measurement. Results: The sample included 2696 patients with T2DM, of which 733 (36.7%) were female, and with a median age of 66 years. The percentage with a current prescription for an antidepressant or benzodiazepine was 22% (95%CI: 18.9-24.9). Those with a current prescription for either drug were more likely to have attended the emergency department (28.3% vs 15.7%, P <0.001), to have been admitted to hospital (35.4% vs 21.3%, P <0.001) in the past year and attend their GP more frequently (median of 9 vs 7, P <0.001) than those without a prescription. Rates of poor glycaemic control were similar in those with and without a current prescription. Conclusion: Over one-fifth of people with T2DM in Irish general practice are prescribed an antidepressant or benzodiazepine medication. Prescription of these is associated with increased healthcare utilization but not poorer glycaemic control.


Assuntos
Antidepressivos/administração & dosagem , Benzodiazepinas/administração & dosagem , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/tratamento farmacológico , Criança , Depressão/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Medicina Geral , Hemoglobina A Glicada/metabolismo , Hospitalização/estatística & dados numéricos , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
15.
Lancet Psychiatry ; 6(9): 745-752, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31303567

RESUMO

BACKGROUND: Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data. METHOD: In this item-based, patient-level, post-hoc analysis, we pooled data from all completed, acute-phase, placebo-controlled, industry-sponsored, HDRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression. Patient-level data were pooled and subjected to item-based post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score, the depressed mood item of the HDRS, a six-item HDRS subscale (HDRS-6), and the remaining 11 HDRS items not included in this subscale (non-HDRS-6). Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more. FINDINGS: Our study population consisted of 8262 patients from 28 placebo-controlled SSRI trials. Participants were treated with either citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine (active-control group; n=754), or placebo (n=2581). 654 patients were defined as having non-severe depression and 1377 as having severe depression. Patients with non-severe and severe depression did not differ with respect to SSRI-induced decrease in depressed mood and other HDRS symptoms belonging to the HDRS-6 subscale. However, after exclusion of patients with rare extreme baseline values, a positive association was seen between severity and efficacy when using HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression than in those with non-severe depression. This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression. INTERPRETATION: The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients. With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression. FUNDING: Swedish Medical Research Council, AFA Insurance, Swedish Brain Foundation, Sahlgrenska University Hospital (Avtal om Läkarutbildning och Forskning), Bertil Hållsten's Foundation, and Söderberg's Foundation.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Citalopram/administração & dosagem , Citalopram/uso terapêutico , Ensaios Clínicos como Assunto , Depressão/psicologia , Transtorno Depressivo Maior/psicologia , Fluoxetina/administração & dosagem , Fluoxetina/uso terapêutico , Humanos , Estudos Longitudinais , Paroxetina/administração & dosagem , Paroxetina/uso terapêutico , Placebos/administração & dosagem , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Reprodutibilidade dos Testes , Inibidores de Captação de Serotonina/administração & dosagem , Sertralina/administração & dosagem , Sertralina/uso terapêutico , Índice de Gravidade de Doença
16.
Pak J Pharm Sci ; 32(3): 1005-1009, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278713

RESUMO

To determine the effects of Salvia hispanica on activities related to memory, anxiety and depression. Albino rats as well as albino mice were utilized in the current study. Two groups of animals were made including 10 animals in each group. One was a control group and another was treated group. Neuropharmacological parameters were assessed using Light and Dark box test, Stationary rod activity, Water maze test, Open field activity and Home cage activity. The control group was maintained on water and treated group was fed with approximately 106 mg/kg extract of Salvia hispanica for 30 days. The observations were recorded on 1st day, 15th day and 30th day. The results of current study showed an increased time spent in the light box of Light and Dark box model, reduction in elapsed time utilized by animal to reach platform in Stationary rod and water maze model, reduced number of peripheral square and central square crosses in the open field and decreased number of cage crosses in the home cage activity. Salvia hispanica shows memory enhancement and also shows an antidepressant activity on chronic administration.


Assuntos
Antidepressivos/farmacologia , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Salvia/química , Administração Oral , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Ratos
17.
Mar Drugs ; 17(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340514

RESUMO

Thirty-four new benzo[d]thiazol derivatives 2a-2i, 3a-3r, and 4a-4g were synthesized and investigated for their potential antidepressant and anticonvulsant effects. In a forced swimming test, 2c and 2d showed the highest antidepressant and anticonvulsant effects. 2c and 2d displayed a higher percentage decrease in immobility duration (89.96% and 89.62%, respectively) than that of fluoxetine (83.62%). In the maximal electroshock seizure test, 3n and 3q showed the highest anticonvulsant effect, with ED50 values of 46.1 and 64.3 mg kg-1, and protective indices of 6.34 and 4.11, respectively, which were similar to those of phenobarbital or valproate. We also found that the mechanism for the antidepressant activity of 2c and 2d may be via increasing the concentrations of serotonin and norepinephrine.


Assuntos
Anticonvulsivantes/administração & dosagem , Antidepressivos/administração & dosagem , Benzotiazóis/administração & dosagem , Produtos Biológicos/farmacologia , Depressão/tratamento farmacológico , Convulsões/tratamento farmacológico , Animais , Regiões Antárticas , Anticonvulsivantes/síntese química , Antidepressivos/síntese química , Organismos Aquáticos/química , Benzotiazóis/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/uso terapêutico , Depressão/etiologia , Depressão/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Eletrochoque/efeitos adversos , Fluoxetina/administração & dosagem , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Penicillium/química , Convulsões/etiologia , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Testes de Toxicidade , Resultado do Tratamento , Ácido Valproico/administração & dosagem
19.
Expert Opin Drug Saf ; 18(8): 679-689, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31159612

RESUMO

INTRODUCTION: Antiepileptic drugs (AEDs) have been associated with a negative impact on bone health. Comorbid disorders in patients with epilepsy may require drugs exerting a pro-osteoporotic effect, so a possibility of untoward interactions with AEDs is probable. AREAS COVERED: This review discusses evidence related to the deteriorating influence of AEDs on bone, demonstrating generally stronger negative effects of conventional AEDs. Lamotrigine seems to be a safer AED in this regard. Further, literature data indicate that generally AEDs can lower the serum concentration of vitamin D. Importantly, pediatric patients are of greater risk of bone problems during therapy with AEDs, which is probably due to their effects on bone-forming processes. EXPERT OPINION: Supplementation with vitamin D and calcium is frequently recommended in patients taking AEDs chronically. Whether to add a bisphosphonate remains an open question due to the limited data on this issue. A possibility of negative interactions exists between AEDs and other pro-osteoporotic drugs: glucocorticoids, proton pump inhibitors and aromatase inhibitors. Depression is a frequent comorbidity in patients with epilepsy. Clinical data indicate that antidepressant drugs may also increase the risk of fractures. Again, patients with epilepsy and depression may be exposed to a greater risk of osteoporosis.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Osteoporose/induzido quimicamente , Adulto , Animais , Anticonvulsivantes/administração & dosagem , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Cálcio/administração & dosagem , Criança , Depressão/tratamento farmacológico , Difosfonatos/administração & dosagem , Interações de Medicamentos , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Fatores de Risco , Vitamina D/administração & dosagem
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