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1.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(11): 108-115, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33340305

RESUMO

However, despite successful use of lithium in the treatment of affective disorders for almost 40 years, the mechanisms of its therapeutic action are still poorly understood. This review presents and summarizes the current literature about the use of lithium in treatment of affective disorders, as well as its effects on cellular physiology, with a separate description of the effect of this ion on the functioning of nerve tissue and ion-molecular mechanisms.


Assuntos
Transtorno Bipolar , Psicofarmacologia , Transtorno Bipolar/tratamento farmacológico , Humanos , Lítio/farmacologia , Lítio/uso terapêutico , Transtornos do Humor/tratamento farmacológico
2.
J Med Chem ; 63(17): 9181-9196, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32787105

RESUMO

Selective inhibitors of the GluN2B subunit of N-methyl-d-aspartate receptors in the ionotropic glutamate receptor superfamily have been targeted for the treatment of mood disorders. We sought to identify structurally novel, brain penetrant, GluN2B-selective inhibitors suitable for evaluation in a clinical setting in patients with major depressive disorder. We identified a new class of negative allosteric modulators of GluN2B that contain a 1,3-dihydro-imidazo[4,5-b]pyridin-2-one core. This series of compounds had poor solubility properties and poor permeability, which was addressed utilizing two approaches. First, a series of structural modifications was conducted which included replacing hydrogen bond donor groups. Second, enabling formulation development was undertaken in which a stable nanosuspension was identified for lead compound 12. Compound 12 was found to have robust target engagement in rat with an ED70 of 1.4 mg/kg. The nanosuspension enabled sufficient margins in preclinical toleration studies to nominate 12 for progression into advanced good laboratory practice studies.


Assuntos
Antipsicóticos/síntese química , Desenho de Fármacos , Imidazóis/química , Piridinas/química , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Regulação Alostérica , Animais , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapêutico , Encéfalo/metabolismo , Cães , Avaliação Pré-Clínica de Medicamentos , Meia-Vida , Humanos , Imidazóis/farmacocinética , Imidazóis/uso terapêutico , Masculino , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/patologia , Nanoestruturas/química , Permeabilidade/efeitos dos fármacos , Piridinas/farmacocinética , Piridinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Solubilidade , Relação Estrutura-Atividade
3.
BMC Psychiatry ; 20(1): 365, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652964

RESUMO

BACKGROUND: The relative benefits and risks of long-term maintenance treatment with antipsychotics have not been well studied in patients with bipolar disorder and major depressive disorder. For example, while antipsychotic dose reduction has been recommended in the management of serious side effects associated with antipsychotics, there is limited evidence on the impact of lowering doses on the course of underlying mood disorders. METHODS: This retrospective cohort study analyzed the impact of antipsychotic dose reduction in patients with bipolar disorder or major depressive disorder. Medical claims from six US states over a 6-year period were analyzed for patients with ≥10% or ≥ 30% reductions in antipsychotic dose (cases) and compared using survival analyses with matched controls receiving a stable dosage. Outcomes included hospitalizations for disease-specific mood disorders, other psychiatric disorders and all-cause emergency room visits, and claims for tardive dyskinesia. RESULTS: A total of 23,992 patients with bipolar disorder and 17,766 with major depressive disorder had a ≥ 10% dose reduction, while 19,308 and 14,728, respectively, had a ≥ 30% dose reduction. In multivariate analyses, cases with a ≥ 10% dose reduction had a significantly increased risk of disease-specific admission (bipolar disorder: hazard ratio [95% confidence interval], 1.22 [1.15-1.31]; major depressive disorder: 1.22 [1.11-1.34]), other psychiatric admission (bipolar disorder: 1.19 [1.13-1.24]; major depressive disorder: 1.17 [1.11-1.23]), all-cause admission (bipolar disorder: 1.17 [1.12-1.23]; major depressive disorder: 1.11 [1.05-1.16]), and all-cause emergency room visits (bipolar disorder: 1.09 [1.05-1.13]; major depressive disorder: 1.07 [1.02-1.11]) (all P <  0.01). Similar results were observed following an ≥30% dose reduction. Dose reduction was not associated with decreased claims for tardive dyskinesia. CONCLUSIONS: Patients with mood disorders who had antipsychotic dose reductions showed small but statistically significant increases in all-cause and mental health-related hospitalizations, which may lead to increased healthcare costs. These results highlight the need for additional long-term studies of the necessity and safety of maintenance antipsychotic treatment in mood disorders.


Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Discinesia Tardia , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Hospitais , Humanos , Transtornos do Humor/tratamento farmacológico , Estudos Retrospectivos , Discinesia Tardia/tratamento farmacológico
4.
Neuron ; 106(5): 715-726, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32497508

RESUMO

Ketamine exerts rapid antidepressant action in depressed and treatment-resistant depressed patients within hours. At the same time, ketamine elicits a unique form of functional synaptic plasticity that shares several attributes and molecular mechanisms with well-characterized forms of homeostatic synaptic scaling. Lithium is a widely used mood stabilizer also proposed to act via synaptic scaling for its antimanic effects. Several studies to date have identified specific forms of homeostatic synaptic plasticity that are elicited by these drugs used to treat neuropsychiatric disorders. In the last two decades, extensive work on homeostatic synaptic plasticity mechanisms have shown that they diverge from classical synaptic plasticity mechanisms that process and store information and thus present a novel avenue for synaptic regulation with limited direct interference with cognitive processes. In this review, we discuss the intersection of the findings from neuropsychiatric treatments and homeostatic plasticity studies to highlight a potentially wider paradigm for treatment advance.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Homeostase/efeitos dos fármacos , Ketamina/farmacologia , Compostos de Lítio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Animais , Antimaníacos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Humanos , Ketamina/uso terapêutico , Compostos de Lítio/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Sinapses/efeitos dos fármacos
5.
Neurotox Res ; 38(1): 1-7, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-244976

RESUMO

As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Doenças do Sistema Nervoso/etiologia , Pneumonia Viral/complicações , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Terapia Combinada , Transtornos da Consciência/epidemiologia , Transtornos da Consciência/etiologia , Infecções por Coronavirus/psicologia , Infecções por Coronavirus/virologia , Tontura/epidemiologia , Tontura/etiologia , Encefalite Viral/epidemiologia , Encefalite Viral/etiologia , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Fadiga/epidemiologia , Fadiga/etiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Hipertensão Intracraniana/epidemiologia , Hipertensão Intracraniana/etiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Transtornos do Humor/etiologia , Transtornos do Humor/terapia , Doenças do Sistema Nervoso/epidemiologia , Neurônios/metabolismo , Neurônios/virologia , Nervo Olfatório/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/psicologia , Pneumonia Viral/virologia , Prevalência , Prognóstico , Psicoterapia , Psicotrópicos/uso terapêutico , Receptores Virais/metabolismo , Estudos Retrospectivos , Transtornos das Sensações/epidemiologia , Transtornos das Sensações/etiologia , Glicoproteína da Espícula de Coronavírus/metabolismo
6.
Neurotox Res ; 38(1): 1-7, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32399719

RESUMO

As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Doenças do Sistema Nervoso/etiologia , Pneumonia Viral/complicações , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Terapia Combinada , Transtornos da Consciência/epidemiologia , Transtornos da Consciência/etiologia , Infecções por Coronavirus/psicologia , Infecções por Coronavirus/virologia , Tontura/epidemiologia , Tontura/etiologia , Encefalite Viral/epidemiologia , Encefalite Viral/etiologia , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Fadiga/epidemiologia , Fadiga/etiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Hipertensão Intracraniana/epidemiologia , Hipertensão Intracraniana/etiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Transtornos do Humor/etiologia , Transtornos do Humor/terapia , Doenças do Sistema Nervoso/epidemiologia , Neurônios/metabolismo , Neurônios/virologia , Nervo Olfatório/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/psicologia , Pneumonia Viral/virologia , Prevalência , Prognóstico , Psicoterapia , Psicotrópicos/uso terapêutico , Receptores Virais/metabolismo , Estudos Retrospectivos , Transtornos das Sensações/epidemiologia , Transtornos das Sensações/etiologia , Glicoproteína da Espícula de Coronavírus/metabolismo
7.
Prog Med Chem ; 59: 63-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362329

RESUMO

P2X7 has continued to be a target of immense interest since it is implicated in several peripheral and central nervous system disorders that result from inflammation. This review primarily describes new P2X7 receptor antagonists that have been investigated and disclosed in patent applications or primary literature since 2015. While a crystal structure of the receptor to aid in the design of novel chemical structures remains elusive, many of the chemotypes that have been disclosed contain similarities, with an amide motif present in all series that have been explored to date. Several of the recent antagonists described are brain penetrant, and two compounds are currently in clinical trials for CNS indications. Additionally, brain penetrant PET ligands have been developed that aid in measuring target engagement and these ligands can potentially be used as biomarkers.


Assuntos
Transtornos do Humor/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Humanos , Ligantes , Estrutura Molecular , Transtornos do Humor/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Antagonistas do Receptor Purinérgico P2X/química
8.
Am J Psychiatry ; 177(6): 497-505, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32252539

RESUMO

OBJECTIVE: Benzodiazepines and Z-drugs are two of the most prescribed agents worldwide. However, because of their cognitive side effects, the question of their influence on the risk of dementia has been raised. The authors examined the association of benzodiazepines, Z-drugs, and other anxiolytics with incident dementia in patients with affective disorders. METHODS: The authors conducted a cohort and nested case-control study of 235,465 patients over age 20 who were identified in the Danish National Patient Registry as having had a first-time hospital contact for an affective disorder between 1996 and 2015. From the Danish National Prescription Registry, information was obtained on all prescriptions for benzodiazepines, Z-drugs, and other anxiolytics, and patients were followed for incident dementia (defined by hospital discharge diagnosis or acetylcholinesterase inhibitor use). Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios and odds ratios with adjustment for sociodemographic and clinical variables. RESULTS: A total of 75.9% (N=171,287) of patients had any use of benzodiazepines or Z-drugs, and during the median follow-up of 6.1 years (interquartile range, 2.7-11), 9,776 (4.2%) patients were diagnosed with dementia. Any use of benzodiazepines or Z-drugs showed no association with dementia after multiple adjustments in either the cohort analysis or a nested case-control design. In the cohort analysis, the number of prescriptions and the cumulated dose of benzodiazepines or Z-drugs at baseline were not associated with dementia. In the nested case-control study, where prescriptions were counted from 1995 until 2 years before the index date, there was a slightly higher odds ratio of dementia in patients with the lowest use of benzodiazepines or Z-drugs (odds ratio=1.08, 95% CI=1.01, 1.15) compared with no lifetime use. However, patients with the highest use had the lowest odds of developing dementia (odds ratio=0.83, 95% CI=0.77, 0.88). CONCLUSIONS: This large cohort study did not reveal associations between use of benzodiazepines or Z-drugs and subsequent dementia, even when exposures were cumulated or divided into long- and short-acting drugs. Some results were compatible with a protective effect.


Assuntos
Ansiolíticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/epidemiologia , Demência/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Estudos de Casos e Controles , Comorbidade , Dinamarca/epidemiologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Diazepam/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Razão de Chances , Oxazepam/uso terapêutico , Piperazinas/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Proteção , Fatores de Risco
9.
Nat Med ; 26(5): 760-768, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32231295

RESUMO

The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach.


Assuntos
Anedonia/efeitos dos fármacos , Benzamidas/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Antagonistas de Entorpecentes/uso terapêutico , Pirrolidinas/uso terapêutico , Receptores Opioides kappa/antagonistas & inibidores , Adulto , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Fármacos do Sistema Nervoso Central/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/psicologia , Estudo de Prova de Conceito , Fatores de Tempo , Resultado do Tratamento
10.
Curr Pharm Des ; 26(20): 2353-2362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32188376

RESUMO

Bipolar disorder and major depression are associated with significant disability, morbidity, and reduced life expectancy. People with mood disorders have shown higher ratios of unhealthy lifestyle choices, including poor diet quality and suboptimal nutrition. Diet and nutrition impact on brain /mental health, but cognitive outcomes have been less researched in psychiatric disorders. Neurocognitive dysfunction is a major driver of social dysfunction and a therapeutic target in mood disorders, although effective cognitive-enhancers are currently lacking. This narrative review aimed to assess the potential cognitive benefits of dietary and nutritional interventions in subjects diagnosed with mood disorders. Eight clinical trials with nutrients were identified, whereas none involved dietary interventions. Efficacy to improve select cognitive deficits has been reported, but results are either preliminary or inconsistent. Methodological recommendations for future cognition trials in the field are advanced. Current evidence and future views are discussed from the perspectives of precision medicine, clinical staging, nutritional psychiatry, and the brain-gut-microbiota axis.


Assuntos
Transtorno Bipolar , Transtornos Cognitivos , Microbioma Gastrointestinal , Dieta , Humanos , Transtornos do Humor/tratamento farmacológico
11.
Sultan Qaboos Univ Med J ; 20(1): e104-e108, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32190378

RESUMO

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency.


Assuntos
Anticonvulsivantes/efeitos adversos , Antipsicóticos/efeitos adversos , Transtornos Neurológicos da Marcha/induzido quimicamente , Doenças Musculares/induzido quimicamente , Ácido Valproico/efeitos adversos , Adolescente , Quimioterapia Combinada , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/psicologia , Feminino , Marcha/efeitos dos fármacos , Humanos , Índia , Transtornos do Humor/complicações , Transtornos do Humor/tratamento farmacológico , Risperidona/efeitos adversos , Triexifenidil/efeitos adversos , Deficiência de Vitamina D
12.
Behav Pharmacol ; 31(2&3): 122-135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32168024

RESUMO

A significant number of patients (30%) do not adequately respond to commonly prescribed antidepressants (e.g. SSRIs, SNRIs, and TCAs). Opioid receptors and their endogenous peptides have demonstrated a clear role in the regulation of mood in animal models and may offer an alternative approach to augment existing therapies. Nevertheless, there is an urgent need to find better ways to predict a patient's response to drug treatment, to improve overall drug responding, and to reduce the time to symptom remission using novel diagnostic and efficacy biomarkers. Cognitive processes, such as perception, attention, memory, and learning, are impaired in patients with mood disorders. These processes can be altered by emotions, a phenomenon called cognitive affective bias. Negative affective biases are a key feature of major depressive disorder (MDD) and may present concurrently with other cognitive deficits. Importantly, a significant percentage of patients report residual cognitive impairments even after effective drug treatment. This approach offers a new opportunity to predict patient treatment responses, potentially improving residual cognitive symptoms and patient outcomes. This review will (1) describe the underlying neurocircuitry of affective cognition and propose how negative biases may occur, (2) outline the role of opioid receptors in affective cognition, executive function, and MDD, and (3) present evidence from the published literature supporting a modulatory role for opioid drugs on negative affective bias, with a focus on kappa-opioid receptor antagonists, currently in development for clinical use for treatment-resistant MDD.


Assuntos
Analgésicos Opioides/farmacologia , Cognição/efeitos dos fármacos , Transtornos do Humor/tratamento farmacológico , Afeto/efeitos dos fármacos , Sintomas Afetivos/tratamento farmacológico , Analgésicos Opioides/metabolismo , Antidepressivos/farmacologia , Atenção/fisiologia , Viés , Transtornos Cognitivos/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Emoções/fisiologia , Função Executiva , Humanos , Aprendizagem , Memória/fisiologia , Transtornos do Humor/fisiopatologia , Testes Neuropsicológicos , Inibidores de Captação de Serotonina/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
13.
Psychiatr Clin North Am ; 43(1): 167-186, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008683

RESUMO

Despite the relatively high prevalence of mixed symptoms and features among patients with mood disorders, the current literature supporting the specific efficacy of second-generation antipsychotics and mood stabilizers for the treatment of mixed symptoms is limited. Several studies have demonstrated that acute affective episodes with mixed symptoms or features tend to respond unsatisfactory to treatments that are usually more effective for the management of other affective phases. There is clearly a need for clinical trials in order to determine the more adequate pharmacologic option for the treatment of individuals suffering from affective episodes with mixed features.


Assuntos
Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtornos do Humor/tratamento farmacológico , Humanos
14.
Psychiatr Clin North Am ; 43(1): 83-93, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008690

RESUMO

Mixed features of the opposite nominal mood-polarity are increasingly recognized in both depressive and [hypo]manic phases of major affective disorders. They are associated with major increases of risk of suicidal behaviors. The authors reviewed the association of suicidal behavior with mixed features in both major depressive and bipolar disorders, as well as potentially relevant adverse effects of antidepressant treatment and use of alternative treatments aimed at minimizing agitation and suicidal risk.


Assuntos
Antipsicóticos/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Ideação Suicida , Antidepressivos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Suicídio/psicologia , Tentativa de Suicídio
16.
Int J Mol Sci ; 21(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093213

RESUMO

BACKGROUND: Neurodegenerative and mood disorders represent growing medical and social problems, many of which are provoked by oxidative stress, disruption in the metabolism of various neurotransmitters, and disturbances in calcium homeostasis. Biologically active plant compounds have been shown to exert a positive impact on the function of calcium in the central nervous system. METHODS: The present paper reviews studies of naturally occurring terpenes and derivatives and the calcium-based aspects of their mechanisms of action, as these are known to act upon a number of targets linked to neurological prophylaxis and therapy. RESULTS: Most of the studied phytochemicals possess anticancer, antioxidative, anti-inflammatory, and neuroprotective properties, and these have been used to reduce the risk of or treat neurological diseases. CONCLUSION: The neuroprotective actions of some phytochemicals may employ mechanisms based on regulation of calcium homeostasis and should be considered as therapeutic agents.


Assuntos
Encéfalo , Cálcio/metabolismo , Carotenoides/uso terapêutico , Monoterpenos/uso terapêutico , Transtornos do Humor , Doenças Neurodegenerativas , Fármacos Neuroprotetores/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/metabolismo , Transtornos do Humor/patologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia
18.
Curr Pharm Des ; 26(2): 236-243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939727

RESUMO

BACKGROUND: The nervous system and the immune system interact consistently in the brain and peripheries. Inflammation in the brain not only alters the metabolism of neurotransmitters, but also causes network dysfunction, structural changes, and the development of mood symptomology in patients with mood disorders. In addition, the dysregulation of the neuroimmune axis in mood disorders drives multiple-system comorbidities. Furthermore, patients with low-grade inflammation are more likely to exhibit treatment resistance with both pharmacotherapy and non-pharmacotherapy. OBJECTIVE: The aim of this review was to examine the available data regarding not only evidence of inflammation in the pathophysiology of mood disorders and their comorbid conditions, but also potential inflammatory biomarkers of mood disorders. METHODS: Studies of the use of adjunct anti-inflammatory medications in mood disorders, and inflammatory biomarkers that may guide treatment outcomes in mood disorders, were summarized. RESULTS: Studies have demonstrated that certain adjunct anti-inflammatory medications might help to improve mood symptoms and reduce comorbidities, and the baseline levels of inflammatory biomarkers, such as peripheral C-reactive protein (CRP), could be used to stratify the treatment outcome. All results suggested that the identification of peripheral and brain inflammatory biomarkers for the diagnosis, outcome prediction, staging, and stratification of interventions of mood disorders has emerged as an important area of translational research in psychiatry. CONCLUSION: Inflammatory biomarkers could guide interventions and enhance treatment response in patients with mood disorders. The main challenge is that substantial complexities might hamper the attainment of this goal.


Assuntos
Biomarcadores , Inflamação , Transtornos do Humor , Anti-Inflamatórios/uso terapêutico , Proteína C-Reativa , Humanos , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Transtornos do Humor/diagnóstico , Transtornos do Humor/tratamento farmacológico
19.
Protein Pept Lett ; 27(6): 449-455, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31868144

RESUMO

Mood disorders include Major Depressive Disorder (MDD), Bipolar Disorder (BD) and variations of both. Mood disorders has a public health significance with high comorbidity, suicidal mortality and economic burden on the health system. Research related to mood disorders has evolved over the years to relate it with systemic conditions. The Renin Angiotensin System (RAS) has been noticed to play major physiological roles beyond renal and cardiovascular systems. Recent studies have linked RAS not only with neuro-immunological processes, but also with psychiatric conditions like mood and anxiety disorders. In this comprehensive review, we integrated basic and clinical studies showing the associations between RAS and mood disorders. Animal studies on mood disorders models - either depression or mania - were focused on the reversal of behavioral and/or cognitive symptoms through the inhibition of RAS components like the Angiotensin- Converting Enzyme (ACE), Angiotensin II Type 1 receptor (AT1) or Mas receptors. ACE polymorphisms, namely insertion-deletion (I/D), were linked to mood disorders and suicidal behavior. Hypertension was associated with neurocognitive deficits in mood disorders, which reversed with RAS inhibition. Low levels of RAS components (renin activity or aldosterone) and mood symptoms improvement with ACE inhibitors or AT1 blockers were also observed in mood disorders. Overall, this review reiterates the strong and under-researched connection between RAS and mood disorders.


Assuntos
Transtornos do Humor/fisiopatologia , Peptidil Dipeptidase A/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Mutação INDEL , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/genética , Transtornos do Humor/metabolismo , Peptidil Dipeptidase A/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos
20.
Artigo em Russo | MEDLINE | ID: mdl-31851169

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Сytoflavin in the treatment of cognitive and emotional disorders in patients with tension headache. MATERIAL AND METHODS: Fifty patients with tension headache, aged from 18 to 50 years, were studied. The following methods and tests were used: neurological examination, NPRS, STAI, CFQ, RAVLT, TOVA, electroencephalography (routine and spectral analysis). The patients were treated with Сytoflavin. RESULTS: After the treatment, clinical improvement was observed in 62.0% of the patients. A significant decrease in trait anxiety and inattention, as well as an improvement of memory performance were observed. A comparative analysis of neurophysiological results before and after the treatment showed a decrease in the manifestations of dysfunction of nonspecific regulation of the brain. CONCLUSION: The results of this study demonstrate the efficacy of Cytoflavin in the treatment of tension headache and associated emotional and cognitive impairments.


Assuntos
Mononucleotídeo de Flavina , Inosina Difosfato , Transtornos do Humor , Niacinamida , Succinatos , Cefaleia do Tipo Tensional , Adolescente , Adulto , Ansiedade , Cognição , Combinação de Medicamentos , Mononucleotídeo de Flavina/uso terapêutico , Humanos , Inosina Difosfato/uso terapêutico , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/tratamento farmacológico , Niacinamida/uso terapêutico , Succinatos/uso terapêutico , Cefaleia do Tipo Tensional/complicações , Cefaleia do Tipo Tensional/tratamento farmacológico , Adulto Jovem
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