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1.
Braz J Psychiatry ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32159712

RESUMO

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. METHODS: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression - Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). RESULTS: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). CONCLUSIONS: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

2.
Int J Mol Sci ; 21(5)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121406

RESUMO

Human cytomegalovirus (HCMV) infections are wide-spread among the general population with manifestations ranging from asymptomatic to severe developmental disabilities in newborns and life-threatening illnesses in individuals with a compromised immune system. Nearly all current drugs suffer from one or more limitations, which emphasizes the critical need to develop new approaches and new molecules. We reasoned that a 'poly-pharmacy' approach relying on simultaneous binding to multiple receptors involved in HCMV entry into host cells could pave the way to a more effective therapeutic outcome. This work presents the study of a synthetic, small molecule displaying pleiotropicity of interactions as a competitive antagonist of viral or cell surface receptors including heparan sulfate proteoglycans and heparan sulfate-binding proteins, which play important roles in HCMV entry and spread. Sulfated pentagalloylglucoside (SPGG), a functional mimetic of heparan sulfate, inhibits HCMV entry into human foreskin fibroblasts and neuroepithelioma cells with high potency. At the same time, SPGG exhibits no toxicity at levels as high as 50-fold more than its inhibition potency. Interestingly, cell-ELISA assays showed downregulation in HCMV immediate-early gene 1 and 2 (IE 1&2) expression in presence of SPGG further supporting inhibition of viral entry. Finally, HCMV foci were observed to decrease significantly in the presence of SPGG suggesting impact on viral spread too. Overall, this work offers the first evidence that pleiotropicity, such as demonstrated by SPGG, may offer a new poly-therapeutic approach toward effective inhibition of HCMV.

3.
Int Clin Psychopharmacol ; 35(2): 113-118, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32004167

RESUMO

Obsessive-compulsive disorder is often associated with schizophrenia and may represent a significant challenge in the treatment as this comorbidity may not respond properly to antipsychotic medication and usually require a pharmacological and psychotherapeutic add-on. In the present case report, we present the case of a 26-year-old male blue-collar subject who developed obsessive-compulsive disorder after a year of complete remission of schizophrenia symptoms under paliperidone long-acting injection that rapidly resolved after low-dosage cariprazine add-on. No adverse effects were reported due to cariprazine- paliperidone long-acting injection combination.

4.
Curr Top Med Chem ; 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32003691

RESUMO

BACKGROUND: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. OBJECTIVE: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. METHODS: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. RESULTS: Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. CONCLUSION: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.

5.
Am J Psychiatry ; 177(1): 76-92, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31623458

RESUMO

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations. CONCLUSIONS: The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient.

6.
Lancet Psychiatry ; 7(1): 52-63, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787585

RESUMO

BACKGROUND: Since people with mental illness are more likely to die from cancer, we assessed whether people with mental illness undergo less cancer screening compared with the general population. METHODS: In this systematic review and meta-analysis, we searched PubMed and PsycINFO, without a language restriction, and hand-searched the reference lists of included studies and previous reviews for observational studies from database inception until May 5, 2019. We included all published studies focusing on any type of cancer screening in patients with mental illness; and studies that reported prevalence of cancer screening in patients, or comparative measures between patients and the general population. The primary outcome was odds ratio (OR) of cancer screening in people with mental illness versus the general population. The Newcastle-Ottawa Scale was used to assess study quality and I2 to assess study heterogeneity. This study is registered with PROSPERO, CRD42018114781. FINDINGS: 47 publications provided data from 46 samples including 4 717 839 individuals (501 559 patients with mental illness, and 4 216 280 controls), of whom 69·85% were women, for screening for breast cancer (k=35; 296 699 individuals with mental illness, 1 023 288 in the general population), cervical cancer (k=29; 295 688 with mental illness, 3 540 408 in general population), colorectal cancer (k=12; 153 283 with mental illness, 2 228 966 in general population), lung and gastric cancer (both k=1; 420 with mental illness, none in general population), ovarian cancer (k=1; 37 with mental illness, none in general population), and prostate cancer (k=6; 52 803 with mental illness, 2 038 916 in general population). Median quality of the included studies was high at 7 (IQR 6-8). Screening was significantly less frequent in people with any mental disease compared with the general population for any cancer (k=37; OR 0·76 [95% CI 0·72-0·79]; I2=98·53% with publication bias of Egger's p value=0·025), breast cancer (k=27; 0·65 [0·60-0·71]; I2=97·58% and no publication bias), cervical cancer (k=23; 0·89 [0·84-0·95]; I2=98·47% and no publication bias), and prostate cancer (k=4; 0·78 [0·70-0·86]; I2=79·68% and no publication bias), but not for colorectal cancer (k=8; 1·02 [0·90-1·15]; I2=97·84% and no publication bias). INTERPRETATION: Despite the increased mortality from cancer in people with mental illness, this population receives less cancer screening compared with that of the general population. Specific approaches should be developed to assist people with mental illness to undergo appropriate cancer screening, especially women with schizophrenia. FUNDING: None.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Detecção Precoce de Câncer/estatística & dados numéricos , Transtornos Mentais/diagnóstico , Neoplasias do Colo do Útero , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Transtornos Mentais/fisiopatologia , Prevalência , Qualidade de Vida , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle
7.
Int J Psychiatry Clin Pract ; : 1-5, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829763

RESUMO

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday 'real world' clinical setting.Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured.Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 'Difficulty in Identifying Feelings' dimension was associated with higher SSI scores.Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. KeypointsPatients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation.The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD.Homocysteine did not correlate with any studied variables.This study was exploratory and cross-sectional: further larger and prospective studies are needed.

9.
Braz J Psychiatry ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31691722

RESUMO

OBJECTIVE: Autistic traits are associated with a burdensome clinical presentation of anorexia nervosa (AN), as is AN with concurrent depression. The aim of the present study was to explore the intertwined association between complex psychopathology combining autistic traits, subthreshold bipolarity, and mixed depression among people with AN. METHOD: Sixty patients with AN and concurrent major depressive episode (mean age, 22.2±7 years) were cross-sectionally assessed using the Autism-Spectrum Quotient test (AQ-test), the Hamilton depression scales for depression and anxiety, the Young Mania Rating Scale (YMRS), the Hypomania-Checklist-32 (HCL-32), second revision (for subthreshold bipolarity), the Brown Assessment and Beliefs Scale (BABS), the Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS), and the Eating Disorder Examination Questionnaire (EDE-Q). Cases were split into two groups depending on body mass index (BMI): severe AN (AN+) if BMI < 16, not severe (AN-) if BMI ≥ 16. RESULTS: The "subthreshold bipolarity with prominent autistic traits" pattern correctly classified 83.6% of AN patients (AN+ = 78.1%; AN- = 91.3%, Exp(B) = 1.391). AN+ cases showed higher rates of positive scores for YMRS items 2 (increased motor activity-energy) and 5 (irritability) compared to AN- cases. CONCLUSIONS: In our sample, depressed patients with severe AN had more pronounced autistic traits and subtly mixed bipolarity. Further studies with larger samples and prospective follow-up of treatment outcomes are warranted to replicate these findings.

11.
JAMA Psychiatry ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577342

RESUMO

Importance: Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified. Objective: To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes. Data Sources: PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019. Evidence Review: Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. Results: Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I2 > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication. Conclusions and Relevance: This study's findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.

12.
Expert Opin Pharmacother ; 20(16): 1925-1933, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31431092

RESUMO

Introduction:Treatment-resistant depression (TRD), seldom interchangeably referred to as 'depression inadequately responding to the standard antidepressant drug,' carries a significant burden. The atypical antipsychotics represent a popular augmentation strategy for antidepressant-resistant depression, although their efficacy/safety profiles vary across different agents and presentations of depression. Areas covered: This review appraises the evidence supporting the use of brexpiprazole augmentation for major depressive disorder (MDD) adults showing an inadequate response to standard antidepressants, covering the related regulatory affairs, and essential pharmacology. Expert opinion: Brexpiprazole is a 'third-generation' antipsychotic featuring dopaminergic D2 and serotonergic 5-HT1A partial agonism approved by the U.S. Food and Drug Administration for the treatment of MDD, besides schizophrenia in adults. The clinical trials leading to the extended approval of brexpiprazole rely on the definition of 'inadequate response' to antidepressants, which seems to poorly represent the most severe cases of TRD seen in clinical practice. TRD definitions appraised in the literature are likewise inconsistent and questionable from a clinical-standpoint. Compared to aripiprazole, brexpiprazole has lower D2 intrinsic activity, although the latter features a more potent serotonergic 5-HT2A antagonism. The actual propensity of brexpiprazole to induce akathisia and tardive dyskinesia warrants assessment by ad-hoc designed long-term, controlled trials.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Quinolonas/uso terapêutico , Tiofenos/uso terapêutico , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Meia-Vida , Humanos , Quinolonas/efeitos adversos , Quinolonas/farmacocinética , Tiofenos/efeitos adversos , Tiofenos/farmacocinética
13.
Artigo em Inglês | MEDLINE | ID: mdl-31402575

RESUMO

AIM: The present study is aimed at revaluating alexithymia, somatic sensations, resilience and their relationships with suicide ideation in drug naïve adult outpatients suffering from first episode major depression (MD). METHODS: Data of 103 adult outpatients (49 men, 56 women) with a diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) diagnosis of MD were analysed. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) and resilience with the 25 items Connor-Davidson Resilience Scale (CD-RISC) whereas depression was evaluated using the 17-item Hamilton Depression Rating Scale, somatic sensations with the Body Sensations Questionnaire and suicide ideation with Scale of Suicide Ideation (SSI). RESULTS: Gender comparisons between all demographic and clinical variables showed no significant differences in all variables. Subjects who were found positive for alexithymia showed higher scores on all clinical variables controlling for age, gender and duration of the current episode. In a linear regression model, lower scores on CD-RISC and Difficulty in Identifying Feelings dimension of TAS-20 were significantly predictive of higher scores on SSI. CONCLUSIONS: Alexithymia and low resilience were significant predictors of increased suicide ideation in a first MD episode. However, study limitations must be considered and future research needs are being discussed.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31436629

RESUMO

Obsessive-compulsive disorder is often associated with schizophrenia and may represent a significant challenge in the treatment as this comorbidity may not respond properly to antipsychotic medication and usually require a pharmacological and psychotherapeutic add-on. In the present case report, we present the case of a 26-year-old male blue-collar subject who developed obsessive-compulsive disorder after a year of complete remission of schizophrenia symptoms under paliperidone long-acting injection that rapidly resolved after low-dosage cariprazine add-on. No adverse effects were reported due to cariprazine- paliperidone long-acting injection combination.

15.
Restor Neurol Neurosci ; 37(3): 265-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31177252

RESUMO

BACKGROUND: In this study, we evaluate the role of RGMa (Repulsive Guidance Molecule a) during peripheral nerve regeneration using the mouse median nerve model. METHODS: By real-time PCR and Western Blot analysis, we examined expression changes of RGMa mRNA and RGMa protein in neural tissue after transection and microsurgical repair of the mouse median nerve distal to the transection site. We evaluated histomorphometrical changes in neural tissue distal to the injury site and functional recovery of the grasping force after median nerve transection and repair in wild-type mice and RGMa+/- heterozygous mice. RESULTS: RT-PCR revealed a 1,8 fold increase of RGMa mRNA two weeks and a 4,4 fold increase of RGMa mRNA 3 weeks after nerve transection and repair in the nerve segment distal to the injury site. In Western blot analysis, we could show a high increase of RGMa in the nerve segment distal to the injury site at day 14. Histomorphometrical analysis showed significant differences between wild-type animals and heterozygous animals. The absolute number of myelinated fibres was significantly higher in operated heterozygous RGMa+/- animals compared to operated wildtye animals. Using the functional grasping test, we could demonstrate that peripheral nerve regeneration is significantly diminished in heterozygous RGMa+/- mice. CONCLUSIONS: Employing the mouse median nerve model in transgenic animals, we demonstrate that RGMa plays an important role during peripheral nerve regeneration.

16.
Front Psychiatry ; 10: 210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057434

RESUMO

Background: Roughly 30% of schizophrenia patients fail to respond to at least two antipsychotic trials. Psychosis has been traditionally considered to be poorly sensitive to psychotherapy. Nevertheless, there is increasing evidence that psychological interventions could be considered in treatment-resistant psychosis (TRP). Despite the relevance of the issue and the emerging neurobiological underpinnings, no systematic reviews have been published. Here, we show a systematic review of psychotherapy interventions in TRP patients of the last 25 years. Methods: The MEDLINE/PubMed, ISI WEB of Knowledge, and Scopus databases were inquired from January 1, 1993, to August 1, 2018, for reports documenting augmentation or substitution with psychotherapy for treatment-resistant schizophrenia (TRS) and TRP patients. Quantitative data fetched by Randomized Controlled Trials (RCTs) were pooled for explorative meta-analysis. Results: Forty-two articles have been found. Cognitive behavioral therapy (CBT) was the most frequently recommended psychotherapy intervention for TRS (studies, n = 32, 76.2%), showing efficacy for general psychopathology and positive symptoms as documented by most of the studies, but with uncertain efficacy on negative symptoms. Other interventions showed similar results. The usefulness of group therapy was supported by the obtained evidence. Few studies focused on negative symptoms. Promising results were also reported for resistant early psychosis. Limitations: Measurement and publication bias due to the intrinsic limitations of the appraised original studies. Conclusions: CBT, psychosocial intervention, supportive counseling, psychodynamic psychotherapy, and other psychological interventions can be recommended for clinical practice. More studies are needed, especially for non-CBT interventions and for all psychotherapies on negative symptoms.

17.
Front Psychiatry ; 10: 294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130881

RESUMO

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications.

18.
Nutrients ; 11(4)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959758

RESUMO

Few studies assessed the associations between dietary vitamin K and depressive symptoms. We aimed to investigate the association between dietary vitamin K and depressive symptoms in a large cohort of North American People. In this cross-sectional analysis, 4,375 participants that were aged 45⁻79 years from the Osteoarthritis Initiative were included. Dietary vitamin K intake was collected through a semi-quantitative food frequency questionnaire and categorized in quartiles. Depressive symptoms were diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16. To investigate the associations between vitamin K intake and depressive symptoms, logistic regression analysis were run, which adjusted for potential confounders. Overall, 437 (=10%) subjects had depressive symptoms. After adjusting for 11 confounders, people with the highest dietary vitamin K intake had lower odds of having depressive symptoms (OR = 0.58; 95%CI: 0.43⁻0.80). This effect was only present in people not taking vitamin D supplementation. In conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders. Future longitudinal research is required to explore the directionality of the association.


Assuntos
Depressão/etiologia , Dieta , Deficiência de Vitamina K/complicações , Vitamina K/administração & dosagem , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Análise de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade
19.
Curr Pharm Des ; 25(4): 381-387, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30864501

RESUMO

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further "neurobiological targeted" approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Fármacos atuantes sobre Aminoácidos Excitatórios/uso terapêutico , Depressão/tratamento farmacológico , Ácido Glutâmico , Humanos , Ketamina , Transmissão Sináptica
20.
Br J Psychiatry ; : 1-10, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30864533

RESUMO

BACKGROUND: The elderly population and numbers of nursing homes residents are growing at a rapid pace globally. Uncertainty exists regarding the actual rates of major depressive disorder (MDD), bipolar disorder and schizophrenia as previous evidence documenting high rates relies on suboptimal methodology.AimsTo carry out a systematic review and meta-analysis on the prevalence and correlates of MDD, bipolar disorder and schizophrenia spectrum disorder among nursing homes residents without dementia. METHOD: Major electronic databases were systematically searched from 1980 to July 2017 for original studies reporting on the prevalence and correlates of MDD among nursing homes residents without dementia. The prevalence of MDD in this population was meta-analysed through random-effects modelling and potential sources of heterogeneity were examined through subgroup/meta-regression analyses. RESULTS: Across 32 observational studies encompassing 13 394 nursing homes residents, 2110 people were diagnosed with MDD, resulting in a pooled prevalence rate of 18.9% (95% CI 14.8-23.8). Heterogeneity was high (I2 = 97%, P≤0.001); no evidence of publication bias was observed. Sensitivity analysis indicated the highest rates of MDD among North American residents (25.4%, 95% CI 18-34.5, P≤0.001). Prevalence of either bipolar disorder or schizophrenia spectrum disorder could not be reliably pooled because of the paucity of data. CONCLUSIONS: MDD is highly prevalent among nursing homes residents without dementia. Efforts towards prevention, early recognition and management of MDD in this population are warranted.Declaration of interestE.V. has received grants and served as consultant, advisor or continuing medical education speaker for the following organisations: AB-Biotics, Allergan, Angelini, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC) and the Stanley Medical Research Institute.

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