Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.032
Filtrar
1.
Adv Exp Med Biol ; 1191: 121-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002926

RESUMO

Discovery of innovative anxiolytics is severely hampering. Existing anxiolytics are developed decades ago and are still the therapeutics of choice. Moreover, lack of new drug targets forecasts a severe jeopardy in the future treatment of the huge population of CNS-diseased patients. We simply lack the knowledge on what is wrong in brains of anxious people (normal and diseased). Translational research, based on interacting clinical and preclinical research, is extremely urgent. In this endeavor, genetic and genomic approaches are part of the spectrum of contributing factors. We focus on three druggable targets: serotonin transporter, 5-HT1A, and GABAA receptors. It is still uncertain whether and how these targets are involved in normal and diseased anxiety processes. For serotonergic anxiolytics, the slow onset of action points to indirect effects leading to plasticity changes in brain systems leading to reduced anxiety. For GABAA benzodiazepine drugs, acute anxiolytic effects are found indicating primary mechanisms directly influencing anxiety processes. Close translational collaboration between fundamental academic and discovery research will lead to badly needed breakthroughs in the search for new anxiolytics.


Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/fisiopatologia , Ansiedade/fisiopatologia , Descoberta de Drogas , Neurotransmissores/metabolismo , Pesquisa Médica Translacional , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/metabolismo , Humanos
2.
Adv Exp Med Biol ; 1191: 169-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002929

RESUMO

This chapter describes the various animal models that seem relevant to the development of anxiolytic drugs, as well as the human models of induced anxiety, or more precisely the panic inducers including cholecystokinin. It is also mentioned the theoretical model of Deakin and Graeff which seems to keep all its relevance. The knock animals are evoked as relevant tools as well as a new optogenetic technique that needs to be used in this field.


Assuntos
Ansiolíticos , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Modelos Animais de Doenças , Descoberta de Drogas , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Colecistocinina/efeitos adversos , Humanos , Optogenética
3.
Medicine (Baltimore) ; 98(50): e18331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852127

RESUMO

This study assessed sex differences in cardiac and motor functions, quality of life (QoL), and mental status in Chinese chronic heart failure (CHF) patients after metoprolol treatment.This single-center prospective study, conducted from February 2013 to April 2016, included CHF patients (men and women) with resting heart rate (HR) >80 beats/min using metoprolol continuous release tablets. Metoprolol-induced changes in cardiac and motor functions, QoL, and mental status at 1, 3, 6, 9, and 12 months from baseline, within and between the sexes, were analyzed. Descriptive data were represented as counts, percentages, and mean ± standard deviation. Differences at various follow-up periods were compared using repeated measures one-way analysis of variance, followed by post hoc Dunnett's multiple comparison test. Statistical significance was considered at P < .05.Compared with men, women reported significantly higher systolic blood pressure (SBP) (122.28 ±â€Š6.76 vs 125.47 ±â€Š6.67 mm Hg, P < .05) and Veterans Specific Activity Questionnaire score (8.16 ±â€Š0.98 vs 8.47 ±â€Š0.89, P = .05) at 12 months. Men reported higher Hospital Anxiety and Depression Scale scores for depression than women at 1 month (10.27 vs 8.83, P < .05) and for anxiety at 12 months (8.4 vs 7.72, P < .05). Metoprolol significantly decreased HR and Minnesota Living with Heart Failure Questionnaire score in men (64.5 ±â€Š3.13 and 53.7 ±â€Š8.00) and women (65.38 ±â€Š3.32 and 53.85 ±â€Š8.42, respectively). Ejection fraction (%, men: 50.00 ±â€Š4.45, women: 50.72 ±â€Š4.09), cardiac index (L/min/m, men: 2.70 ±â€Š0.25, women: 2.78 ±â€Š0.23), 6-minute walk test distance (m, men: 414.41 ±â€Š20.84, women: 420.34 ±â€Š20.35), and short form-8 questionnaire scores (men: 52.05 ±â€Š1.94, women: 52.19 ±â€Š2.58) increased significantly in both the sexes (P < .001 for all) at 12 months. Copenhagen Burnout Inventory score significantly increased in men (mean score 62.43, P < .05).Metoprolol treatment improves cardiac and motor functions, QoL, and anxiety scores but causes greater depression and burnout in men and women. Sex was seen to affect mental status of CHF patients the most.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/psicologia , Metoprolol/uso terapêutico , Qualidade de Vida , Fatores Sexuais , Adulto , Idoso , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Grupo com Ancestrais do Continente Asiático/psicologia , China , Doença Crônica , Depressão/tratamento farmacológico , Depressão/etiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
4.
Harefuah ; 158(11): 711-715, 2019 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-31721512

RESUMO

INTRODUCTION: Burns are one of the most common and painful injuries among babies and children. The pain endured during and in between treatment can be minimized with sedation. These sedations, however, are not without side effects and risks. Given the potential complications, we devised a Burn Analgesic Treatment Protocol that incorporates safe analgesia during burn treatment and throughout the day, thus minimizing the necessity for sedations. AIMS: Assessment of the effectiveness of the analgesic protocol by quantification of overall number of sedations needed for burn treatment and by assessment of the overall experience of the treating medical team exposed to burn care before and after implementation of the protocol. METHODS: A retrospective analysis of analgesic treatment regimens among admitted pediatric burn patients both before and after the implementation of our analgesic protocol was performed. Furthermore, questionnaires were given to the nurses of the treating medical team in order to better assess overall experience with the new analgesic protocol. RESULTS: A total of 87 patients were treated with the new analgesic protocol and 46 patients served as the control group. A significantly lower number of sedations were performed in the group treated with the new protocol compared to the control group (18% vs 30%, p=0.057). The questionnaires filled out by the treating nurses revealed an average score of 4.5 (between 1 - 5), indicating high satisfaction with the protocol. CONCLUSIONS: Our new analgesic protocol allows for highly effective treatment of burn wounds while minimizing the necessity for sedations, thus increasing overall patient safety and reducing potential complications.


Assuntos
Analgésicos , Ansiedade , Queimaduras , Dor , Analgésicos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Queimaduras/complicações , Criança , Humanos , Dor/tratamento farmacológico , Dor/etiologia , Pacientes , Estudos Retrospectivos
5.
Ann Hematol ; 98(12): 2683-2691, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31745600

RESUMO

In Germany, analyses of clinical and laboratory features of patients with acute porphyrias are only available for hereditary coproporphyria (HCP) but not with other acute porphyrias, acute intermittent porphyria (AIP) and variegate porphyria (VP). The aim of the study was to analyze a large cohort of patients with particular focus upon quality of life aspects. Sixty-two individuals from separate families with acute porphyrias (57 AIP, 5 VP) were included into an observational study collecting biochemical, genetic, and clinical data. A questionnaire was designed to complete anamnestic information and to assess the influence on quality of life. Most frequent signs and symptoms or laboratory abnormalities were abdominal colicky pain, red coloration of urine, and hyponatremia. Depression or anxiety was reported by 61% or 52% individuals, respectively. Fatigue was mentioned as the most quality of life-limiting symptom. In 59/61 patients, mutations could be identified. 44% (20/45) had to be admitted to an intensive care unit. Heme arginate was used in 64% (29/45) of patients for treatment of acute attacks at least once and in 33% for long-term treatment with high frequency of administration. Serum creatinine values increased in 47% (7/17) of the patients with recurrent attacks. Our analysis confirms a substantial influence of the diseases on the quality of life on patients. Percentages of urine discoloration and intensive care unit admissions were much higher than in other reports. Long-term treatment with heme arginate requires careful monitoring of iron status and renal values.


Assuntos
Arginina/administração & dosagem , Família , Heme/administração & dosagem , Hospitalização , Porfiria Aguda Intermitente , Qualidade de Vida , Inquéritos e Questionários , Adulto , Ansiedade/tratamento farmacológico , Ansiedade/genética , Ansiedade/metabolismo , Ansiedade/psicologia , Depressão/tratamento farmacológico , Depressão/genética , Depressão/metabolismo , Depressão/psicologia , Feminino , Alemanha , Humanos , Masculino , Porfiria Aguda Intermitente/tratamento farmacológico , Porfiria Aguda Intermitente/genética , Porfiria Aguda Intermitente/metabolismo , Porfiria Aguda Intermitente/psicologia , Estudos Prospectivos
6.
Lancet Psychiatry ; 6(12): 995-1010, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31672337

RESUMO

BACKGROUND: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977). FINDINGS: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis. INTERPRETATION: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed. FUNDING: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.


Assuntos
Ansiedade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Canabinoides/uso terapêutico , Depressão/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Síndrome de Tourette/tratamento farmacológico , Austrália , Dor Crônica/tratamento farmacológico , Humanos
7.
Medicine (Baltimore) ; 98(40): e17375, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577741

RESUMO

Achieving abstinence in schizophrenic smokers using a combination of medications and cognitive behavioral therapy is feasible; however, abstinence rates are significantly lower compared to the general population and studies are scanty. Additionally, maintaining sustained abstinence and preventing relapse is a major limiting factor and represents key tasks in managing tobacco dependence in schizophrenic patients. Several theories have been postulated to explain the higher tendency of tobacco use among schizophrenic individuals. Schizophrenic patients may use nicotine as a "self-medication" strategy to improve negative symptoms of schizophrenia. However, studies suggest that although nicotine may act as an anxiolytic acutely, chronic use of nicotine may lead to increased anxiety with the possibility of increased catecholamines, which is confirmed with the prevalence of tachycardia and hypertension in smokers in general. On this basis, the main objective of our present study was to assess anxiety in schizophrenic smoking and nonsmoking patients by comparing the number of anxiety and agitation episodes and evaluating the amount of antianxiety/antiagitation medication used by each group. A separate objective was to document the unmet needs of smoking cessation programs in treating schizophrenic patients. Consequently, in the present retrospective cohort study, it was observed that schizophrenic smokers tend to have higher anxiety episodes and utilize as-needed medications at a higher frequency compared to nonsmokers for the relief of anxiety and agitation symptoms. Further research is warranted to examine these results on a larger scale.


Assuntos
Ansiedade/epidemiologia , Fumar Cigarros/epidemiologia , Esquizofrenia/epidemiologia , Ansiolíticos/uso terapêutico , Antipsicóticos/uso terapêutico , Ansiedade/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Fumantes , Abandono do Hábito de Fumar/métodos
8.
J Pediatr Orthop ; 39(10): 500-504, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31599858

RESUMO

BACKGROUND: Opioids are commonly used after posterior spinal instrumented fusion (PSIF) for adolescent idiopathic scoliosis (AIS). Prescription opioids use can potentially lead to misuse, abuse, dependence, and overdose death. Prolonged opioid use has not been extensively studied in the postoperative AIS population. The purpose of this study is to identify risk factors associated with prolonged opioid use after PSIF for AIS. METHODS: A large insurance database was queried for AIS patients undergoing PSIF. Patients with prolonged postoperative opioid use were defined as those receiving new prescriptions for an opioid medication >6 weeks following the date of surgery, up to 8 months postoperatively. Preoperative and intraoperative risk factors for prolonged opioid use were then examined, including the number of spinal levels fused, preoperative opioid prescriptions, demographic variables, pertinent comorbidities (anxiety, depression, attention deficit hyperactivity disorder, and autism) and other preoperative prescriptions (anxiolytics, antidepressants, nonopioid analgesics, neuropathic medications, and attention deficit hyperactivity disorder medications). Each variable's independent risk for prolonged postoperative opioid use was examined utilizing a multivariable binomial regression analysis. P<0.05 was considered statistically significant. RESULTS: A total of 511 patients were included in the study. Of this 50 patients (9.78%) were found to have prolonged opioid use following scoliosis surgery. Preoperative opioid use (odds ratio, 2.93; P<0.001) was the most significant predictor of prolonged postoperative opioid use. In addition, female sex, obesity, a preoperative diagnosis of anxiety and a preoperative prescription for a muscle relaxer were also significant positive risk factors for prolonged postoperative opioid use. Several factors were found to be protective against prolonged postoperative opioid use. Fewer total fusion levels, compared with ≥13 levels, had a significantly lower risk of prolonged opioid use. Preoperative anxiolytic and antidepressant use were also both negative predictors of prolonged opioid use. CONCLUSIONS: Efforts at addressing preoperative opioid use, anxiety, obesity, and providing multimodal pain management strategies should be considered to reduce additional postoperative opioid prescriptions after PSIF for AIS. LEVEL OF EVIDENCE: Level III-retrospective comparative study.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Escoliose/epidemiologia , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Demandas Administrativas em Assistência à Saúde , Adolescente , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/epidemiologia , Criança , Comorbidade , Feminino , Humanos , Masculino , Relaxantes Musculares Centrais/uso terapêutico , Obesidade/epidemiologia , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Período Pré-Operatório , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
9.
Medicine (Baltimore) ; 98(37): e17186, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517876

RESUMO

BACKGROUND: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. METHODS: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. RESULTS: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). CONCLUSIONS: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Adulto , Ansiolíticos/efeitos adversos , Ansiedade/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/efeitos adversos , Estresse Psicológico/metabolismo , Testosterona/metabolismo , Resultado do Tratamento
10.
Nutrients ; 11(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527485

RESUMO

A systematic review and meta-analysis was undertaken to examine and quantify the effects of B vitamin supplementation on mood in both healthy and 'at-risk' populations. A systematic search identified all available randomised controlled trials (RCTs) of daily supplementation with ≥3 B group vitamins with an intervention period of at least four weeks. Random effects models for a standardized mean difference were used to test for overall effect. Heterogeneity was tested using the I2 statistic. Eighteen articles (16 trials, 2015 participants) were included, of which 12 were eligible for meta-analysis. Eleven of the 18 articles reported a positive effect for B vitamins over a placebo for overall mood or a facet of mood. Of the eight studies in 'at-risk' cohorts, five found a significant benefit to mood. Regarding individual facets of mood, B vitamin supplementation benefited stress (n = 958, SMD = 0.23, 95% CI = 0.02, 0.45, p = 0.03). A benefit to depressive symptoms did not reach significance (n = 568, SMD = 0.15, 95% CI = -0.01, 0.32, p = 0.07), and there was no effect on anxiety (n = 562, SMD = 0.03, 95% CI = -0.13, 0.20, p = 0.71). The review provides evidence for the benefit of B vitamin supplementation in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety. B vitamin supplementation may particularly benefit populations who are at risk due to (1) poor nutrient status or (2) poor mood status.


Assuntos
Afeto/efeitos dos fármacos , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Suplementos Nutricionais , Estresse Psicológico/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Deficiência de Vitaminas do Complexo B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Resultado do Tratamento , Complexo Vitamínico B/efeitos adversos , Deficiência de Vitaminas do Complexo B/diagnóstico , Deficiência de Vitaminas do Complexo B/epidemiologia , Deficiência de Vitaminas do Complexo B/psicologia , Adulto Jovem
11.
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
13.
Mediators Inflamm ; 2019: 4315038, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396018

RESUMO

Patients with diabetes mellitus (DM) showed an increased risk of anxiety. High anxiety levels are also shown to increase stress of diabetic patients, which may contribute to poor clinical outcomes. The mechanisms underlying the development of anxiety disorders in diabetic patients remain unknown. As a result, there are no available treatments yet. Here, we tested the hypothesis that glial cells in the hippocampal area of DM mice might be responsible for their anxiety-like behaviors. Furthermore, we postulated that treatment with antidepressant, fluoxetine, could reduce anxiety behaviors and prevent the dysregulation of glial cells (oligodendrocyte and astrocyte) in DM mice. Diabetic mice were administered a single injection of streptozotocin (STZ), followed by treatment with fluoxetine. Mice were then tested on Y maze, open field, dark and light transition, and elevated plus maze tests to measure the status of anxiety and cognition. After completing these behavioral tests, mice were sacrificed and western blot was used to detect the oligodendrocyte and astrocyte maker proteins in hippocampal tissues. Emphasis was directed towards adult oligodendrocyte precursor cells (OPCs) and their marker protein to measure their proliferation and differentiation. We found that fluoxetine could effectively mitigate the level of anxiety and attenuate the cognitive dysfunction in diabetic mice. Meanwhile, fluoxetine inhibited astrocyte activation in mice exposed to STZ, prevented the loss of myelin basic protein (MBP), and affected the function of OPCs in these diabetic mice. The results suggested that the changes of these glial cells in the brains of diabetic mice might be related to the high anxiety levels and cognitive deficit in DM mice. Fluoxetine could ameliorate the high anxiety level and prevent cognitive deficit via inhibiting astrocyte activation and repairing the oligodendrocyte damage.


Assuntos
Ansiedade/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Fluoxetina/uso terapêutico , Inflamação/tratamento farmacológico , Animais , Antidepressivos/uso terapêutico , Ansiedade/imunologia , Western Blotting , Diabetes Mellitus Experimental/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/imunologia , Interleucina-6/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
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.
Riv Psichiatr ; 54(4): 137-149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379379

RESUMO

AIM: To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder. METHODS: Medline and Cochrane Library searches were searched using the keywords 'trazodone' AND 'depression', to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice. RESULTS: Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects. DISCUSSION: Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation. CONCLUSIONS: Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.


Assuntos
Antidepressivos de Segunda Geração , Transtorno Depressivo Maior/tratamento farmacológico , Trazodona , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/metabolismo , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Ansiedade/tratamento farmacológico , Bulimia/tratamento farmacológico , Preparações de Ação Retardada , Interações de Medicamentos , Fibromialgia/tratamento farmacológico , Humanos , Transtornos Neurocognitivos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Trazodona/efeitos adversos , Trazodona/metabolismo , Trazodona/farmacologia , Trazodona/uso terapêutico
16.
Biomed Pharmacother ; 118: 109276, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377466

RESUMO

BACKGROUND: Paeonia lactiflora (PL) was widely used for pain relief, but its effects on migraine headaches remain unclear. PURPOSE: The aim of the present study was to investigate the effects of PL on migraine headaches. METHODS: First, we found that PL was frequently used in Taiwan for headache treatment based on data from Taiwan's National Health Insurance Research Database. Migraine was induced through the intraperitoneal injection (i.p.) of nitroglycerin (NTG, 10 mg/kg) in rats. Pretreatment with PL was administered orally 30 min prior to the NTG i.p. Migraine headache behavior was observed by video-recordings. Finally, the rats were sacrificed and brain was removed for immunohistochemistry staining analysis. RESULTS: The frequency and total time spent rearing up and sniffing in exploratory behavior, and walking in locomotor behavior, were reduced in the NTG group compared with the control group (all p <  0.001). This reduction could be ameliorated by pretreatment with PL 1.0 g/kg (all p <  0.05). Total time spent in the light chamber was lower in the NTG group compared with the control group (p <  0.05); this could be ameliorated by pretreatment with 1.0 g/kg PL (p <  0.05). The rats in the NTG group spent longer time on the smooth surface than those in the control group (p <  0.001); this could be shortened by pretreatment with 0.5 and 1.0 g/kg PL (both p <  0.01). The traveling distance of rats in the NTG group was shorter than in the control group (p <  0.001); rats given 1.0 g/kg PL had a longer traveling distance than those in the NTG group (p <  0.01). Both c-fos and CGRP immunoreactive cells increased in the TNC in the NTG group compared with that of the control group (both p <  0.001); this increased could be reduced by pretreatment with PL 0.5 and 1.0 g/kg (both p <  0.05). CONCLUSION: Pretreatment with PL ameliorated migraine headache behaviors in the NTG-induced migraine rat model, suggesting pretreatment with PL is beneficial for migraine headache treatment. This effect of PL is related to the decrease of c-fos and CGRP in the TNC. However, still there are too many methodological limitations which need to be overcome in further experiments to support the data.


Assuntos
Comportamento Animal , Medicamentos de Ervas Chinesas/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Paeonia/química , Animais , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Depressão/complicações , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Reação de Congelamento Cataléptica , Asseio Animal , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Imobilização , Masculino , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/fisiopatologia , Atividade Motora/efeitos dos fármacos , Nitroglicerina , Dor/tratamento farmacológico , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-Dawley , Sono , Núcleos do Trigêmeo/efeitos dos fármacos , Núcleos do Trigêmeo/patologia , Núcleos do Trigêmeo/fisiopatologia
17.
Nat Commun ; 10(1): 3768, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434877

RESUMO

The etiology of major depressive disorder (MDD), the leading cause of worldwide disability, is unknown. The neurogenic hypothesis proposes that MDD is linked to impairments of adult neurogenesis in the hippocampal dentate gyrus (DG), while the effects of antidepressants are mediated by increased neurogenesis. However, alterations in neurogenesis and endophenotypes are not always causally linked, and the relationship between increased neurogenesis and altered behavior is controversial. To address causality, we used chemogenetics in transgenic mice to selectively manipulate activity of newborn DG neurons. Suppressing excitability of newborn neurons without altering neurogenesis abolish the antidepressant effects of fluoxetine. Remarkably, activating these neurons is sufficient to alleviate depression-like behavior and reverse the adverse effects of unpredictable chronic mild stress. Our results demonstrate a direct causal relationship between newborn neuronal activity and affective behavior. Thus, strategies that target not only neurogenesis but also activity of newborn neurons may lead to more effective antidepressants.


Assuntos
Antidepressivos/farmacologia , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Fluoxetina/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
18.
Biol Pharm Bull ; 42(8): 1268-1274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366864

RESUMO

Increasing evidence shows depression relevant to oxidative stress and inflammation. Anti-inflammatory strategies or antioxidants have led to the development of new antidepressants. Brazilin is a natural product from the Chinese traditional medicine Caesalpinia sappan L., exerting anti-inflammatory, antioxidant, anti-platelet concentration, and anti-cancer effects. While the antidepressant effect of brazilin is largely unknown. In present study, we investigated the effects of brazilin on H2O2-induced oxidative injury in PC12 cells and on depression- and anxiety-like behaviors of chronically mild stressed (CMS)-induced depression mice. It was found that brazilin pre-treatment (both 10 and 20 µM) significantly increased cell viability and decreased cell apoptosis in H2O2-treated PC12 cells. Furthermore, repetitive administration of brazilin to CMS-induced depression mice by intraperitoneal injection (10 mg/kg) made the mice significantly lose their latency of feeding in novelty-suppressed feeding test (NSF), have more the sucrose preference in sucrose preference test (SPT), and more time spent in the central zone without affecting their crossing activity in open field test (OFT). These results suggested that brazilin can play a role in antidepressant and anxiolytic-like behaviors for CMS-induced depression mice probably through inhibiting the oxidative stress. Therefore, brazilin is worth to be further explored for treating depressive and anxiety disorders.


Assuntos
Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Benzopiranos/uso terapêutico , Depressão/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzopiranos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos
19.
Food Funct ; 10(9): 5544-5554, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424471

RESUMO

This study compared the abilities of γ-[Glu]n-Trp (EW) and whey protein hydrolysate (WPH) with a high ratio of Trp : 5 large neutral amino acids (5LNAAs) to reverse chronic restraint stress-corticosterone injection induced anxiety/depression-like behaviors in C57BL/6 male mice. EW was synthesized using l-glutaminase from Bacillus amyloliquefaciens. Acid protease, trypsin, pancreatin or flavorzyme was used to produce WPHs. The WPH with the highest Trp/5LNAAs ratio (17.38%; by trypsin) was selected for animal trials. EW (dose 2.0, 5.0 or 10.0 mg kg-1 d-1) and WPH (dose 0.5, 1.0 or 2.0 mg g-1 d-1) reversed behavioral dysfunctions, suppressed serum inflammatory cytokines (TNF-α, IL-6, IL-1ß and IFN-γ), and reduced the activity of indoleamine 2,3-dioxygenase (key rate-limiting enzyme of the kynurenine pathway) while increasing the activity of tryptophan hydroxylase (key rate-limiting enzyme of the serotonin pathway) in the hypothalamus, hippocampus and prefrontal cortex, with EW acting more effectively. EW could also increase body weight gain and might act more effectively via the kynurenine pathway. These findings are of significance to promote the future practical application of kokumi γ-[Glu]n-Trp peptides.


Assuntos
Anti-Inflamatórios/administração & dosagem , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Animais , Ansiedade/genética , Ansiedade/imunologia , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Depressão/genética , Depressão/imunologia , Depressão/psicologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/imunologia , Triptofano/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas do Soro do Leite/química
20.
Oxid Med Cell Longev ; 2019: 6869350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428228

RESUMO

Our previous study has demonstrated the effects of aqueous extract of lily bulb in alleviating menopause-related psychiatric symptoms in ovariectomized (OVX) mice. This study sought to further investigate the psychotropic effects of total polysaccharides of lily bulb (TPLB) against anxiety, depression, and cognitive deterioration and the underlying mechanisms in OVX mice using behavioral, neurochemical, molecular, and proteomic approaches in comparison with estrogen therapy. While TPLB and estradiol showed similar effects in reducing OVX-induced anxiety, depression, and cognitive impairment, the psychotropic effects of TPLB were more closely associated with the predominant activation of estrogen receptors (ERs) and regulation of brain regional neurotransmitters and neurotrophins with minor effects on the uterus. Estradiol had similar potencies in binding affinity at ERα and ERß, which caused widespread genetic and epigenetic effects. In contrast, TPLB displayed a higher affinity at ERß than ERα, triggering the specific Ras/Akt/ERK/CREB signaling pathway without affecting any epigenetic activity. TPLB additionally modulated multiple proteins associated with mitochondrial oxidative stress, but estradiol did not. These results indicate that TPLB has comparable efficacy in reducing menopause-associated neuropsychological symptoms with a better safety profile compared to estrogen therapy. We suggest that TPLB could serve as a novel agent for menopause syndrome.


Assuntos
Lilium/metabolismo , Menopausa/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Estradiol/metabolismo , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/química , Receptor beta de Estrogênio/metabolismo , Feminino , Fulvestranto/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/análise , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA