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1.
J Agric Food Chem ; 67(45): 12441-12451, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31674783

RESUMO

Sesamin, a lignan from sesame seed, has been reported to attenuate chronic mild stress-induced depressive-like behaviors. Gut microbiota play pivotal roles in mediating psychological behaviors by regulating gut barrier integrity and systemic inflammatory responses. Here, we found that oral sesamin administration (50 mg/kg·bodyweight/day) significantly attenuated depressive, aversive, repetitive, and anxiety-like behaviors in a long-term multiple nonsocial stress-treated mice model. Sesamin inhibited stress-induced gut barrier integrity damage, reduced circulating lipopolysaccharide (LPS) levels, and suppressed neuroinflammatory responses. Moreover, sesamin treatment also restructured the gut microbiome by enhancing the relative abundances of Bacteroidales and S24-7. The correlation analysis indicated that the microbiota composition changes were strongly correlated with behavioral disorders, serotonin, norepinephrine, and LPS levels. In conclusion, sesamin has preventive effects on stress-induced behavioral and psychological disorders, which might be highly related to the reshaped microbiota composition. This study provides a clue for understanding the systemic mechanism of anti-depression effects of sesamin.


Assuntos
Depressão/tratamento farmacológico , Suplementos Nutricionais/análise , Dioxóis/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Lignanas/administração & dosagem , Extratos Vegetais/administração & dosagem , Sesamum/química , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Comportamento/efeitos dos fármacos , Depressão/microbiologia , Depressão/psicologia , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Sementes/química , Estresse Psicológico
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 672-678, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762236

RESUMO

OBJECTIVE: To determine the impact olanzapine (OLA) on the hippocampal neuron of model rats with depression. METHODS: Rats were divided into five groups: control, chronic unpredicted stress (CUS), OAL (0.5, 1, 2 mg/kg), si-Atg5, and OAL (2 mg/kg)+si-Atg5. Open field and sucrose preference tests were performed to evaluate rat behaviors. Cell apoptosis was detected with Tunnel. The concentrations of interleukin (IL)-1ß and IL-18 were determined by ELISA. The expressions of cleaved Caspase-3, cleaved Caspase-9, LC3, Beclin1, P62, NLRP3 and cleaved Caspase-1 were measured by Western blot. RESULTS: OAL (0.5, 1, 2 mg/kg) increased the total moving distance, sucrose consumption and preference rate of CUS rats, and decreased serum IL-18, cell apoptosis and the expressions of cleaved Caspase-9, cleaved Caspase-1 and NLRP3 in the CA3 region of hippocampus. Although OAL (1, 2 mg/kg) decreased the expression of cleaved Caspase-3 and serum IL-1ß, OAL (0.5 mg/kg) showed no detectable effects. Si-Atg5 decreased the total moving distance, sucrose consumption and preference rate of CUS rats, enhanced the expressions of cleaved Caspase-3, cleaved Caspase-9, cleaved Caspase-1 and NLRP3, and weakened the effect of OAL (2 mg/kg). OAL (0.5, 1, 2 mg/kg) also increased the LC3Ⅱ/LC3Ⅰ ratio and the expression of Beclin1 in the CA3 region of hippocampus. OAL (1, 2 mg/kg) reduced the expression of p62, but not when it was reduced to 0.5 mg/kg. Si-Atg5 reduced the LC3Ⅱ/LC3Ⅰ ratio and the expression of Beclin1, and weakened the function of OAL (2 mg/kg). CONCLUSION: OAL can protect the hippocampal neuron of CUS rats via inhibiting NLRP3 inflammasome activation.


Assuntos
Depressão/tratamento farmacológico , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Olanzapina/farmacologia , Animais , Hipocampo/citologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos
3.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3343-3348, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602893

RESUMO

To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Hipotálamo/efeitos dos fármacos , Neurotransmissores/química , Animais , Cromatografia Líquida , Hipotálamo/química , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
5.
Shanghai Kou Qiang Yi Xue ; 28(3): 312-316, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489422

RESUMO

PURPOSE: To investigate the clinical effect and safety of modified Xiaoyao pill on the treatment of oral lichen planus (OLP) patients with anxiety or depression. METHODS: Sixty OLP patients with anxiety and depression were randomly divided into 2 groups, treated separately with hydroxychloroquine(HCQ, control group) and HCQ+modified Xiaoyao pill(experimental group). The results were measured with semi quantitative reticular erosive and ulcerative lesion (REU) and visual analogue scale(VAS) scoring system at the first visit, the second week, the fourth week and the eighth week, respectively. Data analysis was performed using SPSS 18.0 software package. RESULTS: The clinical effect of HCQ+modified Xiaoyao pill was better than that of the HCQ. The REU, VAS scores were lower after treatment in both groups (P<0.05), but the effect of the experimental group was more remarkable in reducing the pain indexes, accelerating the healing of erosive lesion and preventing recurrence than the control group. There was no significant difference in the overall effective rate between the two groups (P>0.05). CONCLUSIONS: Modified Xiaoyao pill was effective and safe in the treatment of OLP patients with anxiety or depression, especially for EOLP.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Líquen Plano Bucal , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Depressão/complicações , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Líquen Plano Bucal/psicologia
6.
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
8.
Psychiatr Danub ; 31(Suppl 3): 252-257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488736

RESUMO

Major depression is one of the most frequent psychiatric conditions. Despite many available treatment methods, more than 30% of patients do not achieve remission, even after trying several antidepressants and augmentation strategies. S-enantiomer of ketamine, well-known anesthetic and analgesic, has been recently approved by Food and Drug Administration in the intranasal form as a new generation antidepressant. However, the mechanism in which ketamine reduces depressive symptoms in treatment-resistant depression patients is still not completely understood. There are several theories explaining how ketamine might reduce depressive symptoms, which have been described in detail; one of them is immunomodulatory effect of ketamine, according to the inflammatory theory of depression. In the review authors present and summarize studies showing ketamine effect on human immune system ex vivo and in vitro, including changes in cytokine levels, number, ratio and activity of various immune cell population and the correlation with clinical improvement in depressive symptoms. Most of the results confirm the anti-inflammatory effect of ketamine. There are only a few studies in the population of patients suffering from depression receiving ketamine, focused on correlation between immunological changes and clinical outcome of the therapy; further studies of that area are neccesary for understanding the immunomodulatory effect of ketamine in depression.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/imunologia , Ketamina/imunologia , Ketamina/uso terapêutico , Antidepressivos/imunologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/imunologia , Humanos , Imunomodulação/imunologia
9.
Psychiatr Danub ; 31(Suppl 3): 258-260, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488737

RESUMO

Suicidal ideations or attempts in patients with major depressive disorder (MDD) are emergent conditions that require immediate treatment. Numerous therapeutic interventions to reduce suicide risk in psychiatric disorders are effective in long-term suicide prevention, but there is necessity of sufficient, rapid pharmacological treatment of suicidal risk in MDD. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has been reported to have rapid antidepressant effect. Depressive symptoms, anxiety, hopelessness, suicidal ideation had decreased within hours after ketamine infusion. Ketamine's rapid symptoms relief and reduction of suicide thoughts has aroused growing interests in psychiatric association.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Suicídio/prevenção & controle , Depressão/tratamento farmacológico , Depressão/psicologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Humanos , Ideação Suicida , Suicídio/psicologia
10.
Psychiatr Danub ; 31(Suppl 3): 530-533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488786

RESUMO

Major depressive disorder (MDD) is a recurrent, incapacitating psychiatric illness which will be the second most disabling disease worldwide by the year 2020. There is a rising promise in a N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, which may be used in the treatment of resistant depression. Many of the studies are in favor of the drug, even in single dose application, with effects appearing in minutes to hours from administration. However, there is a need to evaluate the benefits and risks regarding psychomimetic, psychiatric, neurologic, and cognitive adverse effects of ketamine administration. The most distressing symptoms which appear most frequently during ketamine administration are dissociative symptoms, which can be quantified as a CNS adverse drug reaction. Results generally show that a single infusion of ketamine is efficacious and well-tolerated, while dissociative symptoms tend to abate within 2 hours after ketamine administration. As studies show single doses of ketamine should be definitely considered as an option in TRD patients with/without suicidal thoughts, even though it could not provide remission, or the effect could be temporary, but improving patients' quality of life by reducing depressive symptomatology should be a major asset while considering this particular procedure, particularly in inpatients.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Depressão/tratamento farmacológico , Humanos , Qualidade de Vida
11.
Psychiatr Danub ; 31(Suppl 3): 549-553, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488789

RESUMO

Depression affects over 121 million people annually worldwide. Relatively low remission rates among depressive patients enforce the search for new therapeutic solutions and an urgent need to develop faster-acting antidepressants with a different mechanism of action occurs. The pathomechanism of depression postulated by the monoamine hypothesis is limited. The results of abnormalities in glutamate and γ-aminobutyric acid (GABA) systems in the brains of people with mood disorders allowed to develop new theories regarding pathophysiology of these disorders. Glutamatergic transmission is influenced by magnesium and ketamine through glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonistic effects. Magnesium and ketamine have a common mechanism of action in the treatment of depression: an increase in GluN2B (NMDAR subunit) expression is related to the administration of both of the agents, as well as inhibition of phosphorylation of eEF2 (eukaryotic elongation factor 2) in cell culture and increase of the expression of BDNF in the hippocampus. Combination of ketamine and magnesium in a normal magnesium level presents a superadditive effect in depression treatment. Analysed substances affect the GABAergic system and have anti-inflammatory effects, which is correlated with their antidepressant effect. The synergistic interaction between the pharmacodynamic activity of magnesium and ketamine may be of particular importance for patients with mood disorders. Further research is needed to determine the relationship between magnesium levels and ketamine treatment response mainly in the attempt to establish if the magnesium supplementation can change ketamine treatment response time or present superadditive effect.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Ketamina/uso terapêutico , Magnésio/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Humanos , Fator 2 de Elongação de Peptídeos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
12.
Psychiatr Danub ; 31(Suppl 3): 554-560, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488790

RESUMO

Bipolar depression (BD) is among the most severe psychiatric disorders. A significant number of patients do not achieve an entirely symptom-free state and experience residual sub-syndromal depression. Most of the treatment options approved for bipolar depression give no rapid symptom improvement. Ketamine is an anaesthetic medication that acts as an antagonist of the NMDA receptor and has antidepressant potential. Due to its unique way of action, ketamine seems to be crucial for the treatment of anhedonia. This review paper aims to provide an overview of the efficacy of ketamine infusions in bipolar depression with a focus on anhedonia Literature suggests that intravenous ketamine 0.5 mg/kg over 40 min weekly could be useful in the treatment of bipolar depression with prominent anhedonia, but there is still a small number of studies that examine the efficacy of ketamine infusions in BD. In conclusion, ketamine should be considered as a valuable treatment option for patients with BD and anhedonia.


Assuntos
Anedonia/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Depressão/complicações , Depressão/tratamento farmacológico , Ketamina/farmacologia , Ketamina/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Bipolar/complicações , Humanos
13.
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
14.
Lancet Psychiatry ; 6(9): 735-744, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31371212

RESUMO

BACKGROUND: Medication is commonly used to treat youth depression, but whether medication should be added to cognitive behavioural therapy (CBT) as first-line treatment is unclear. We aimed to examine whether combined treatment with CBT and fluoxetine was more effective than CBT and placebo in youth with moderate-to-severe major depressive disorder. METHODS: The Youth Depression Alleviation-Combined Treatment (YoDA-C) trial was a randomised, double-blind, placebo-controlled, multicentre clinical trial. Participants were aged 15-25 years with moderate-to-severe MDD and had sought care at one of four clinical centres in metropolitan Melbourne, Australia. Patients were randomly assigned (1:1) to receive CBT for 12 weeks, plus either fluoxetine or placebo. Participants began on one 20 mg capsule of fluoxetine or one placebo pill per day. All participants received CBT, delivered by therapists in weekly 50-minute sessions and attended interviews at baseline, and at weeks 4, 8, and 12, during which they completed assessments with research assistants. Participants saw a psychiatrist or psychiatry trainee to complete medical assessments at the same timepoints. The primary outcome was change in the interviewer-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score at 12 weeks. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001281886). FINDINGS: 153 participants (mean age 19·6 years [SD 2·7]) were enrolled from Feb 20, 2013, to Dec 13, 2016. 77 (50%) patients were allocated to CBT and placebo and 76 (50%) to CBT and fluoxetine. Participants had severe depression at baseline (mean MADRS score 33·6 [SD 5·1] in the CBT and placebo group and 32·2 [5·6] in the CBT and fluoxetine group), with high proportions of participants with anxiety disorder comorbidity (47 [61%] in the CBT and placebo group and 49 [64%] in the CBT and fluoxetine group) and past-month suicidal ideation (55 [71%] in the CBT and placebo group and 59 [78%] in the CBT and fluoxetine group). 59 (77%) participants in the CBT and placebo group and 64 (84%) in the CBT and fluoxetine group completed follow-up at week 12. After 12 weeks of treatment both groups showed a reduction in MADRS scores (-13·7, 95% CI -16·0 to -11·4, in the CBT and placebo group and -15·1, -17·4 to -12·9, in the CBT and fluoxetine group). There was no significant between-group difference in MADRS scores (-1·4, -4·7 to 1·8; p=0·39). There were five suicide attempts in the CBT and placebo group and one suicide attempt in the CBT and fluoxetine group (odds ratio 0·2, 0·0-1·8; p=0·21), and no significant between-group differences for other suicidal behaviours. INTERPRETATION: We did not find evidence that the addition of fluoxetine (rather than placebo) to CBT further reduced depressive symptoms in young people with moderate-to-severe MDD. Exploratory analyses showed that the addition of medication might be helpful for patients with comorbid anxiety symptoms and for older youth. FUNDING: Australian National Health and Medical Research Council.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Terapia Combinada/métodos , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Fluoxetina/uso terapêutico , Adolescente , Adulto , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Ansiedade/terapia , Austrália/epidemiologia , Comorbidade , Depressão/terapia , Transtorno Depressivo Maior/terapia , Método Duplo-Cego , Feminino , Fluoxetina/administração & dosagem , Humanos , Masculino , Inibidores de Captação de Serotonina/uso terapêutico , Ideação Suicida , Resultado do Tratamento , Adulto Jovem
15.
Life Sci ; 234: 116751, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415771

RESUMO

AIMS: The present study aims to investigate the impacts of olfactory bulbectomy (OBX) on urinary metabolic profile and tryptophan metabolites in prefrontal cortex (PFC) of rats, and to explore the regulation effects of fluoxetine. MAIN METHODS: OBX model was developed by aspiration of olfactory bulbs. After fluoxetine treatment (10 mg/kg) for 14 days, urine samples were collected and behavior tests were applied. Tryptophan (TRP) metabolites and neurotransmitters in PFC were determined by prominence ultrafast liquid chromatography-QTRAP-mass spectrometry, and tryptophan hydroxylase 2 (TPH2) and indoleamine-2,3-dioxygenase 1 (IDO1) were evaluated by western blot. Urinary metabolites were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabonomics strategy. KEY FINDING: OBX rats showed hyperlocomotion in open field, hyperactivity in open arm and despair status, and fluoxetine reserved these behavioral abnormalities. The levels of TRP, 5-HIAA, 5-HIAA/5-HT ratio and DA increased, while kynurenine and 5-HT decreased in PFC of OBX rats. The activities of TPH2 and IDO1were inhibited after OBX. Twenty-six altered metabolites were identified as potential biomarkers in OBX rats involved in tryptophan metabolism, gut microbiota metabolism, energy metabolism, purine metabolism, ascorbate and aldarate metabolism, and tyrosine metabolism. Among them, 15 abnormal metabolites were corrected by fluoxetine to some extent. SIGNIFICANCE: Our results revealed that urinary metabolic profile changed greatly in OBX rats, and identified biomarkers might be helpful for the diagnosis of agitated depression. The regulation effects of fluoxetine on urinary metabolic profile and tryptophan metabolites in PFC might contribute to its antidepressant action in OBX rats.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Depressão/tratamento farmacológico , Depressão/metabolismo , Fluoxetina/uso terapêutico , Metaboloma/efeitos dos fármacos , Animais , Antidepressivos de Segunda Geração/farmacologia , Depressão/urina , Modelos Animais de Doenças , Fluoxetina/farmacologia , Masculino , Bulbo Olfatório/cirurgia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos Sprague-Dawley , Triptofano/metabolismo
16.
Artigo em Russo | MEDLINE | ID: mdl-31464295

RESUMO

The authors discuss the relationship between depression and cognitive impairment in the aspect of mechanisms of their development, variants of comorbidity and recommendations on differentiated therapy in elderly. The diagnostic differentiation between depression and dementia at different stages of dementia as well as in younger and older ages, a role of depression as a risk factor for dementia, a role of other factors, in particular age, as well as treatment approaches on the example of antidepressants and cerebrolysin are considered.


Assuntos
Disfunção Cognitiva , Demência , Depressão , Transtorno Depressivo , Idoso , Antidepressivos/uso terapêutico , Disfunção Cognitiva/complicações , Depressão/complicações , Depressão/tratamento farmacológico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Humanos , Pessoa de Meia-Idade
18.
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 , Avaliação de Resultados (Cuidados de Saúde) , 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
19.
AIDS Behav ; 23(Suppl 2): 153-161, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317365

RESUMO

Despite widespread HIV screening and treatment programs across sub-Saharan Africa, many countries are not on course to meet the Joint United Nations Program on HIV/AIDS 90-90-90 targets. As mental health disorders such as depression are prevalent among people living with HIV, investment in understanding and addressing comorbid depression is increasing. This manuscript aims to assess depression and HIV management in sub-Saharan Africa using a 90-90-90 lens through a discussion of: depression and the HIV care continuum; the state of depression screening and treatment; and innovations such as task-shifting strategies for depression management. Due to the lack of mental health infrastructure and human resources, task-shifting approaches that integrate mental health management into existing primary and community health programs are increasingly being piloted and adopted across the region. Greater integration of such mental health care task-shifting into HIV programs will be critical to realizing the 90-90-90 goals and ending the HIV epidemic.


Assuntos
Antidepressivos/uso terapêutico , Serviços de Saúde Comunitária/organização & administração , Continuidade da Assistência ao Paciente , Prestação Integrada de Cuidados de Saúde/organização & administração , Depressão/diagnóstico , Depressão/tratamento farmacológico , Infecções por HIV/psicologia , Programas de Rastreamento/métodos , África ao Sul do Saara/epidemiologia , Depressão/etiologia , Depressão/psicologia , Transtorno Depressivo/epidemiologia , Metas , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Adesão à Medicação , Prevalência , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Nações Unidas
20.
Expert Opin Pharmacother ; 20(15): 1837-1845, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31355688

RESUMO

Introduction: Although postnatal depression is now well recognized, there is also a risk of depressive symptoms during perimenopause. The mechanisms underlying perimenopausal depression are still poorly understood; however, there are available treatment options. Areas covered: This review describes: the current pharmacotherapeutic approaches for perimenopausal depression, their strengths and weakness, and provides recommendations on how current treatment can be improved in the future. An electronic search identified specific guidelines for the treatment of perimenopausal depression released in 2018, as well as recent clinical studies on the subject. Expert opinion: The 2018 guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) as front-line medications for perimenopausal depression, but SSRIs and SNRIs are not always effective. The efficacy of estrogen in perimenopausal depression is well documented, but estrogen is not FDA-approved to treat mood disturbances in perimenopausal women. Clinical practice guidelines currently recommend to restrict hormone therapy to the symptomatic treatment of menopause (not for the prevention of chronic diseases). Research with new estrogenic compounds is under way to improve their benefit/risk ratio in perimenopausal depression.


Assuntos
Depressão/tratamento farmacológico , Perimenopausa/psicologia , Inibidores de Captação de Serotonina/uso terapêutico , Depressão/patologia , Feminino , Humanos , Inibidores de Captação de Serotonina/farmacologia
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