Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.086
Filtrar
1.
Psychiatr Danub ; 31(Suppl 3): 486-489, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488777

RESUMO

Mixed states are often underdiagnosed, with important consequences in terms of worsening prognosis, frequent admission to the hospital, higher suicide risk and poorer quality of life. For this reason, we analyzed retrospective data from patients admitted in the Psychiatric Hospital from January 1st to April 30th 2019 to identify clinical features of the mixed states by administering the G.T. MSRS scale. Within the 90 subjects of the sample, the large majority (75%) met criteria for mixed state. Of those only 16 were discharged with a diagnosis of Affective Disorder, however 26 (30.9%) were prescribed a mood stabilizer. This study shows that there is a high prevalence of mixed states in the inpatient unit admission, which is demonstrated both from the prescription of mood stabilizers, and confirmed by the diagnosis of mixed states rated with the scale. The scale can be a useful instrument to detect early in the course if the hospitalization the presence of mixed state, in order to guide a tailored psychopharmacological treatment, and improve prognosis.


Assuntos
Pacientes Internados/psicologia , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Unidade Hospitalar de Psiquiatria , Humanos , Transtornos do Humor/tratamento farmacológico , Prognóstico , Qualidade de Vida , Estudos Retrospectivos
2.
Codas ; 31(3): e20180111, 2019 Jun 27.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31271579

RESUMO

PURPOSE: to analyze the occurrence of psychiatric diagnosis and the use of psychotropics medications in subjects with vestibular complaints and to relate the presence of these conditions to the results of vestibulometry. METHODS: quantitative, observational, cross-sectional study with 131 patients, treated in a university hospital. They were submitted to anamnesis, visual inspection of the external ear canal, static and dynamic balance tests, Foam laser dynamic posturography and Computerized Vectoelectronystagmography. RESULTS: sample composed of 109 women and 22 men, with average age of 55 years and nine months. The most common type of dizziness was vertigo, with the presence of neurovegetative signals. A significant percentage of psychiatric complaint/diagnosis was observed, as well as the use of psychotropic medications, mainly serotonin uptake inhibitors, followed by benzodiazepines. There was a relation between the presence of psychiatric complaints with the female gender, alterations of the static balance and alterations in the Sensorial Organization Test positions III and VI. In the Vectoelectronystagmography, there was a relation between age and the presence of spontaneous nystagmus. CONCLUSION: There was a high occurrence of psychiatric complaint/diagnosis among patients with dizziness, with use of psychotropic medications substantially greater than the general population. The evaluation of postural balance revealed an association between anxiety/depression and alterations visual overload positions in the foam laser dynamic posturography. However, no relationship was found between these conditions and alterations in the Vectoelectronystagmography tests.


Assuntos
Tontura/induzido quimicamente , Transtornos do Humor/tratamento farmacológico , Equilíbrio Postural/efeitos dos fármacos , Psicotrópicos/efeitos adversos , Vertigem/induzido quimicamente , Testes de Função Vestibular/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Psicotrópicos/classificação , Estudos Retrospectivos , Adulto Jovem
3.
Expert Opin Pharmacother ; 20(12): 1421-1427, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180743

RESUMO

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a reported prevalence of 1 in 59 people. Its core features are persistent deficits in social communication and restricted, repetitive patterns of behavior or interests. Individuals with ASD have a high incidence of secondary problems with mood lability, tantrums, self-injurious behavior and aggressiveness toward others. Collectively, these behaviors are often referred to as irritability. Many medications have been used to treat irritability in autism, with aripiprazole one of only two medications approved in the USA for this purpose. Areas covered: Herein, the authors review the evidence supporting the use of aripiprazole for treating irritability in autism, including the pivotal trials leading to regulatory approval and long-term studies conducted post-approval. They utilized PubMed, searching all English language publications since 2000, using the terms aripiprazole, autism, autism spectrum disorder, pervasive developmental disorder, Asperger's disorder, and irritability, and focused on clinical trials and review articles. Expert opinion: Multiple studies have shown the clear benefit of aripiprazole in the treatment of irritability in autism disorders compared to placebo. Often underemphasized are the metabolic effects, the proper monitoring for these effects, and the need for periodic reassessment to determine if ongoing treatment is needed.


Assuntos
Aripiprazol/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/psicologia , Humor Irritável/efeitos dos fármacos , Transtornos do Humor/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Comunicação , Humanos , Transtornos do Humor/epidemiologia , Transtornos do Humor/etiologia , Resultado do Tratamento
4.
Nutrients ; 11(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30986970

RESUMO

Cognitive impairment is strongly associated with functional outcomes in psychiatric patients. Involvement of n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), in particular docosahexaenoic acid (DHA), in brain functions is largely documented. DHA is incorporated into membrane phospholipids as structural component, especially in the central nervous system where it also has important functional effects. The aim of this review is to investigate the relationship between DHA and cognitive function in relation to mental disorders. Results from few randomized controlled trials (RCTs) on the effects of DHA (alone or in combination) in psychotic, mood and neurodevelopmental disorders, respectively, suggest that no conclusive remarks can be drawn.


Assuntos
Encéfalo/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Afeto/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Ácidos Docosa-Hexaenoicos/metabolismo , Humanos , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/metabolismo , Transtornos do Humor/fisiopatologia , Transtornos do Humor/psicologia , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/psicologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-30717435

RESUMO

Mental Disorders and Heroin Use Disorder (HUD) often co-occur and constitute correlated risk factors that the authors believe are best considered from a unitary perspective. In this article we review and discuss data collected by the V.P. Dole Research Group in Dual Disorder (V.P. Dole DD-RG) patients according to the following six discussion points: (1) Treatment of personality disorders during Methadone Maintenance Treatment (MMT); (2) Treatment of Mood Disorders during MMT; (3) Treatment of Anxiety Disorders during MMT; (4) Treatment of Psychotic Disorders during MMT; (5) Treatment of violence during MMT; (6) Treatment of Alcohol Use Disorder (AUD) during MMT. In treating Mood Disorder in HUD patients, we must bear in mind the interactions (potentiation and side effects) between psychopharmacology, used substances and agonist opioid medications; the use of psychiatric medications as an anti-craving drug, and the possible use of agonist and antagonist opioid medications in treating the other mental disorders. In treating chronic psychosis in HUD patients, we must consider the potentiation and side effects of antipsychotic drugs consequent on HUD treatment, worsening addiction hypophoria and inducing a more severe reward deficiency syndrome (RDS) in hypophoric patients. Violence and AUD during MMT can benefit from adequate dosages of methadone and co-medication with Sodium gamma-hydroxybutyrate (GHB). The experience of our V.P. Dole DD-RG suggests the following: (a) DD is the new paradigm in neuroscience in deepening our understanding of mental health; (b) To successfully treat DD patients a double competence is needed; (c) In managing DD patients priority must be given to Substance Use Disorder (SUD) treatment (stabilizing patients); (d) Antidepressant use is ancillary to SUD treatment; antipsychotic use must be restricted to acute phases; mood stabilizers must be preferred; any use of Benzodiazepines (BDZs) must be avoided.


Assuntos
Dependência de Heroína/tratamento farmacológico , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Alcoolismo/tratamento farmacológico , Alcoolismo/epidemiologia , Antidepressivos , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Fissura/efeitos dos fármacos , Interações de Medicamentos , Dependência de Heroína/epidemiologia , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Violência/estatística & dados numéricos
6.
Trials ; 20(1): 120, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755265

RESUMO

BACKGROUND: The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour. METHODS: The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737. DISCUSSION: The results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected. TRIAL REGISTRATION: ISRCTN, ISRCTN33631053 . Retrospectively registered on 8 June 2018 (applied 17 May 2018).


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Cognição/efeitos dos fármacos , Transtornos do Humor/tratamento farmacológico , Nicardipino/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono/efeitos dos fármacos , Adolescente , Adulto , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/genética , Método Duplo-Cego , Humanos , Imagem por Ressonância Magnética , Magnetoencefalografia , Adulto Jovem
7.
J Affect Disord ; 249: 96-103, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30769297

RESUMO

BACKGROUND: Mood disorders can be difficult to treat during pregnancy. There is still lack of evidence whether pregnancy influences their natural course and whether continuation of pharmacotherapy, despite potential risks for the unborn child, is beneficial in preventing recurrence of mood episodes during pregnancy. METHODS: Systematic review conducted according to the PRISMA guidelines, searching Pubmed, PsycINFO, Embase and Cochrane databases up till January 9th, 2018. Recurrence rates and various measures of risk were calculated. RESULTS: Out of 1387 articles from an initial search 22 studies met the inclusion criteria. Included studies reported a wide variation in the recurrence rate of bipolar disorder and major depressive disorder during pregnancy (BD: mean = 19%, range = 4%-73%; MDD: mean = 8%, range = 1%-75%). Observational data showed a relative risk reduction of maintenance therapy during pregnancy of 66% in women with BD and 54% for women with MDD, a significant difference (95% CI 9.4-14.6; p < 0.001). LIMITATIONS: heterogeneous samples, study designs, and reported outcomes in included studies. CONCLUSIONS: Despite the importance of the topic there is a paucity of evidence on recurrence rates of mood episodes during pregnancy among women with MDD or BD. Unlike the impact of the postpartum period, it is still uncertain whether the course of mood disorders is influenced by pregnancy. Non-randomized studies show that maintenance pharmacotherapy during pregnancy in women with mood disorders significantly (p < 0.01) reduces the risk of recurrence.


Assuntos
Transtornos do Humor/diagnóstico , Complicações na Gravidez/diagnóstico , Adulto , Antipsicóticos/uso terapêutico , Feminino , Humanos , Transtornos do Humor/tratamento farmacológico , Período Pós-Parto , Gravidez , Complicações na Gravidez/tratamento farmacológico , Recidiva , Risco , Fatores de Risco
8.
PLoS One ; 14(2): e0211873, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730956

RESUMO

Psychiatric comorbidities are common in individuals with attention-deficit/hyperactivity disorder (ADHD). In this study, we sought to evaluate the effects of medication and childhood ADHD subtypes on psychiatric comorbidities among adults with ADHD as compared to healthy adult controls. We assessed 121 drug-naïve adults with ADHD, 93 treated adults with ADHD, and 145 healthy controls (age 18-36 years) using semi-structured psychiatric interviews, intelligence tests, and medical records. Drug-naïve adults with ADHD had more comorbidities than treated adults with ADHD and controls. Childhood ADHD-combined subtype, relative to ADHD-inattentive subtype, was associated with higher risks of comorbidities. Current medication treatment was associate with a higher risk for anxiety disorders, and longer treatment duration was associated with lower risks of mood disorders and sleep disorders. Our results indicate that no medication treatment, short treatment duration, and childhood ADHD-combined subtype are associated with increased risks for psychiatric comorbidities among adults with ADHD.


Assuntos
Transtornos de Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos do Humor/psicologia , Transtornos do Sono-Vigília/psicologia , Adolescente , Adulto , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/patologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/patologia , Testes Neuropsicológicos , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/patologia , Adulto Jovem
9.
Cell Tissue Res ; 377(1): 45-58, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30649612

RESUMO

Studies about the pathogenesis of mood disorders have consistently shown that multiple factors, including genetic and environmental, play a crucial role on their development and neurobiology. Multiple pathological theories have been proposed, of which several ultimately affects or is a consequence of dysfunction in brain neuroplasticity and homeostatic mechanisms. However, current clinical available pharmacological intervention, which is predominantly monoamine-based, suffers from a partial and lacking response even after weeks of continuous treatment. These issues raise the need for better understanding of aetiologies and brain abnormalities in depression, as well as developing novel treatment strategies. Nitric oxide (NO) is a gaseous unconventional neurotransmitter, which regulates and governs several important physiological functions in the central nervous system, including processes, which can be associated with the development of mood disorders. This review will present general aspects of the NO system in depression, highlighting potential targets that may be utilized and further explored as novel therapeutic targets in the future pharmacotherapy of depression. In particular, the review will link the importance of neuroplasticity mechanisms governed by NO to a possible molecular basis for the antidepressant effects.


Assuntos
Antidepressivos/farmacologia , Encéfalo , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/metabolismo , Neurotransmissores/farmacologia , Óxido Nítrico/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Humanos , Camundongos , Plasticidade Neuronal , Ratos , Transdução de Sinais
10.
Drug Discov Today ; 24(2): 606-615, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30447328

RESUMO

Mood disorders represent the largest cause of disability worldwide. The monoaminergic deficiency hypothesis, which has dominated the conceptual framework for researching the pathophysiology of mood disorders and the development of novel treatment strategies, cannot fully explain the underlying neurobiology of mood disorders. Mounting evidence collected over the past two decades suggests the amino acid neurotransmitter systems (glutamate and GABA) serve central roles in the pathophysiology of mood disorders. Here, we review progress in the development of compounds that act on these systems as well as their purported mechanisms of action. We include glutamate-targeting drugs, such as racemic ketamine, esketamine, lanicemine (AZD6765), traxoprodil (CP-101,606), EVT-101, rislenemdaz (CERC-301/MK-0657), AVP-786, AXS-05, rapastinel (formerly GLYX-13), apimostinel (NRX-1074/AGN-241660), AV-101, NRX-101, basimglurant (RO4917523), decoglurant (RG-1578/RO4995819), tulrampator (CX-1632/S-47445), and riluzole; and GABA-targeting agents, such as brexanolone (SAGE-547), ganaxolone, and SAGE-217.


Assuntos
Antidepressivos/uso terapêutico , Ácido Glutâmico/metabolismo , Transtornos do Humor/tratamento farmacológico , Ácido gama-Aminobutírico/metabolismo , Animais , Humanos , Transtornos do Humor/metabolismo
11.
J Neurol Sci ; 396: 78-83, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30423541

RESUMO

Depression is the most common psychiatric complication in patients with Parkinson's disease (PD). Istradefylline, a new anti-parkinsonian agent with completely different mechanism, improves depression-like symptoms in an experimental disease model; however, there is no report of its effects in PD patients. In this study, the effectiveness of istradefylline for treatment of mood disorders in patients with PD was examined in an open-label trial. Thirty PD patients were enrolled. All patients had scores of higher than cut-off level in at least one of the following batteries: Snaith-Hamilton Pleasure Scale Japanese version (SHAPS-J), Apathy scale, or Beck Depression Inventory-2nd edition (BDI). Following study enrollment, all patients received 20 mg of istradefylline, and the dose was increased to 40 mg after 4 weeks. Results from these 3 batteries and the Unified Parkinson's Disease Rating Scale (UPDRS) score were assessed every 2-4 weeks until 12 weeks and the changes in these scores were analyzed. Following administration of istradefylline, the scores of SHAPS-J, Apathy scale, and BDI were significantly improved over time. Significant improvement was also found in the UPDRS score; however, no significant correlation was observed between the score change in these 3 batteries and UPDRS motor function. This is the first study to show the effectiveness of istradefylline for treatment of mood disorders in PD independent of improvement of parkinsonian motor symptoms. In the future, this should be confirmed in a double-blind placebo-controlled trial.


Assuntos
Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/etiologia , Doença de Parkinson/complicações , Purinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Apatia/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Resultado do Tratamento
12.
Biomed Pharmacother ; 109: 1148-1162, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551365

RESUMO

Anxiety and depression, the most prevalent psychiatric disorders are co-morbid in nature affecting several people across the world. There is an increase in demand for complementary and alternative medicines, specifically herbal botanicals due to various side effects exhibited by conventional drugs. Herbal drugs mentioned in traditional medicines, face acceptance issues by the medical community due to lack of scientific data regarding their neurochemical pathways. Hence, there has been an increased interest in the quest to unravel the mechanisms of action of herbal psychotropics. With the advancements in "omic technologies" such as genomics, proteomics and metabolomics, research in the field of herbal psychopharmacology has gained momentum, providing a faster and informative platform for thorough evaluation of herbal drugs and formulations. In this article, we have reviewed several medicinal plants and their formulations that have shown potential anxiolytic and anti-depressant activities and have been screened for their biological mechanisms either at the gene, protein or metabolic level.


Assuntos
Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/genética , Medicina Herbária/métodos , Humanos , Farmacogenética/métodos
13.
Pharmacol Rep ; 71(1): 112-120, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30544098

RESUMO

A contemporary model for the pathogenesis of mood disorders (bipolar and depressive disorders) involves gene-environmental interaction, with genetic predisposition, epigenetic regulation, and environmental effects. Among multiple environmental factors, the experience of childhood trauma can be connected with the pathogenesis, course and the treatment of mood disorders. Patients with mood disorders have the greater frequency of childhood trauma compared with the general population, and adverse childhood experiences can exert a negative impact on their clinical course. In this article, the neurobiological mechanisms of childhood trauma are presented. The influence of negative childhood experiences on the central nervous system can result in many structural and functional changes of the brain, including such structures as hippocampus and amygdala, associated with the development of bipolar and depressive illnesses. Interaction of several genes with childhood trauma to produce pathological, clinical phenomena in adulthood has been demonstrated, the most important in this respect being the serotonin transporter gene and the FKBP5 gene playing an important role in the pathogenesis of mood disorders. Neurobiological effects can also involve epigenetic mechanisms such as DNA methylation which can exert an effect on brain function over long-term periods. Somatic effects of childhood trauma include disturbances of stress axis and immune-inflammatory mechanisms as well as metabolic dysregulation. Negative childhood experiences may also bear implications for the treatment of mood disorders. In the article, the impact of such experiences on the treatment of mood disorders will be discussed, especially in the context of treatment -resistance to antidepressants and mood-stabilizing drugs.


Assuntos
Afeto , Encéfalo/fisiopatologia , Maus-Tratos Infantis/psicologia , Comportamento Infantil , Acontecimentos que Mudam a Vida , Transtornos do Humor/fisiopatologia , Transtornos do Humor/psicologia , Adulto , Afeto/efeitos dos fármacos , Fatores Etários , Animais , Luto , Encéfalo/efeitos dos fármacos , Criança , Desenvolvimento Infantil , Divórcio/psicologia , Emoções , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/genética , Fenótipo , Fatores de Risco
14.
Neuropsychobiology ; 77(2): 67-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30544110

RESUMO

Several antipsychotics and antidepressants have been associated with electrocardiogram alterations, the most clinically relevant of which is the heart rate-corrected QT interval (QTc) prolongation, a risk factor for sudden cardiac death. Genetic variants influence drug-induced QTc prolongation and can provide valuable information for precision medicine. The effect of genetic variants on QTc prolongation as well as the possible interaction between polymorphisms and risk medications in determining QTc prolongation were investigated. Medications were classified according to their known risk of inducing QTc prolongation (high-to-moderate, low, and no risk). QTc duration and risk of QTc > median value were investigated in a sample of 77 patients with mood or psychotic disorders being treated with antidepressants and antipsychotics, and who had at least 1 ECG recording. A secondary analysis considered QTc percentage change in patients (n = 25) with 2 ECG recordings. Single-nucleotide polymorphisms previously associated with QTc prolongation during treatment with psychotropic medications were investigated. No association survived after multiple-testing correction. The best results for modulation of QTc duration were identified for rs10808071 (the ABCB1 gene, nominal p = 0.007) when at least 1 medication with a moderate-to-high risk was prescribed, and for rs12029454 (the NOS1AP gene) in patients taking at least 1 medication with a cardiovascular risk (nominal p = 0.008). In the secondary analysis, rs2072413 (the KCNH2 gene) was the top finding for the modulation of QTc percentage change (nominal p = 0.001) when 1 drug with a moderate-to-high risk was added compared to baseline. Despite the limited power of this study, our results suggest that ABCB1, NOS1AP, and KCNH2 may play a role in QTc duration/prolongation during treatment with psychotropic drugs.


Assuntos
Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Eletrocardiografia , Coração/efeitos dos fármacos , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Canal de Potássio ERG1/genética , Estudos de Associação Genética , Coração/fisiopatologia , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/fisiopatologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/fisiopatologia
15.
Psychiatry Clin Neurosci ; 73(4): 175-178, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30552718

RESUMO

AIMS: Non-adherence or partial adherence to psychotropic medication is found in 18-70% of patients. Many previously used methods for the assessment of adherence (e.g. questionnaires, pill counts, and electronic systems), however, might underreport actual rates of non-adherence to medication. The aim of this study was to quantify adherence using plasma level. METHODS: We conducted a 6-week prospective study of all consecutive admitted patients at the Paracelsus Medical University of Salzburg, Clinics of Psychiatry and Psychotherapy, who had been treated with antipsychotics/antidepressants prior to admission (pre-medication dosage in 161 of 233). Plasma drug levels were determined and compared with expected levels based on known preadmission dosing regimens and average pharmacokinetic data. RESULTS: Seventy-three percent of the patients had actual plasma levels clearly below or above the intended level. Significantly more patients with schizophrenia (66%) did not take the medication as prescribed, when compared with patients with affective disorders (47%) or those with other psychiatric diagnoses (41%). Only 27% (44 of 161) of the patients had plasma level in the expected range based on the dosage. CONCLUSION: The risk of partial adherence or non-adherence is expected in two-thirds of patients with schizophrenia, half of patients with affective disorders, and approximately 40% of patients with other psychiatric diagnoses. Given that admitting psychiatrists could not provide an accurate assessment of patient adherence, it is strongly suggested that clinical judgment be supplemented with the actual monitoring of adherence - and further optimization of pharmacotherapy - by means of therapeutic drug monitoring.


Assuntos
Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Hospitais Psiquiátricos , Adesão à Medicação , Transtornos Mentais/tratamento farmacológico , Transtornos do Humor/tratamento farmacológico , Admissão do Paciente , Esquizofrenia/tratamento farmacológico , Adulto , Antidepressivos/sangue , Antipsicóticos/sangue , Feminino , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Transtornos Mentais/sangue , Pessoa de Meia-Idade , Transtornos do Humor/sangue , Admissão do Paciente/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Esquizofrenia/sangue
16.
Mol Psychiatry ; 24(4): 576-587, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29955162

RESUMO

The United States is in the midst of an opioid addiction and overdose crisis precipitated and exacerbated by use of prescription opioid medicines. The majority of opioid prescriptions are dispensed to patients with comorbid mood disorders including major depressive disorder (MDD). A growing body of research indicates that the endogenous opioid system is directly involved in the regulation of mood and is dysregulated in MDD. This involvement of the endogenous opioid system may underlie the disproportionate use of opioids among patients with mood disorders. Emerging approaches to address endogenous opioid dysregulation in MDD may yield novel therapeutics that have a low or absent risk of abuse and addiction relative to µ-opioid agonists. Moreover, agents targeting the endogenous opioid system would be expected to yield clinical benefits qualitatively different from conventional monaminergic antidepressants. The development of safe and effective agents to treat MDD-associated endogenous opioid dysregulation may represent a distinct and currently underappreciated means of addressing treatment resistant depression with the potential to attenuate the on-going opioid crisis.


Assuntos
Analgésicos Opioides/metabolismo , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Depressão/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Overdose de Drogas , Humanos , Transtornos do Humor/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides , Medicamentos sob Prescrição , Estados Unidos
18.
Behav Brain Res ; 359: 845-852, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30041006

RESUMO

Postmenopausal depression has been shown to be related to the reduction of ovarian hormones produced as a woman transitions from a menopausal to a post-menopausal stage. What remains to be known is which type of estrogen receptor plays a key role in estrogen neuroprotection, a process that may be mediated by potentiating brain mitochondrial function and inhibiting mitochondria-associated apoptosis. In order to better imitate the condition of postmenopause, we conducted our research on aged female rats. Plasma estrogen levels declined significantly in ovariectomized rats and 16-month-old female rats, while anxiety and depression-like behavior increase. Moreover, ERα, ERß, GPER, Bcl2 and UCP2 expression decreased significantly in hippocampus in female rats following ovariectomy. In our study, the anxiety and depression-like behavior in aged female rats were significantly relieved after the treatment of G-1, the GPER agonist. Furthermore, G-1 could reverse the reduction of ERα, ERß, GPER, Bcl2 and UCP2 expression within the hippocampus. Mitochondrial JC-1 staining indicated that mitochondrial membrane potential increased after G-1 treatment. In addition, total antioxidant capacity (TAC) and superoxide dismutase activity (SOD) were found to be elevated in aged female rats following G-1 treatment. Taken together, estrogen receptors, especially GPER, may activate anti-apoptotic signaling and accelerate mitochondrial function. Therefore, GPER could be the potential therapeutic target for estrogen deficiency-related affective disorders.


Assuntos
Envelhecimento/efeitos dos fármacos , Ciclopentanos/farmacologia , Hipocampo/efeitos dos fármacos , Transtornos do Humor/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Quinolinas/farmacologia , Receptores Estrogênicos/metabolismo , Animais , Modelos Animais de Doenças , Estrogênios/sangue , Comportamento Exploratório/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/ultraestrutura , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Natação/psicologia
19.
J Affect Disord ; 246: 217-223, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30583148

RESUMO

BACKGROUND: Few studies have assessed the treatment of tardive dyskinesia (TD) in patients with primary mood disorders who are managed with antipsychotics. The effects of once-daily valbenazine on TD were evaluated in adults with a bipolar or depressive disorder. METHODS: Data were pooled from two 6-week double-blind placebo-controlled trials (KINECT 2 and KINECT 3; 114 mood participants) and a long-term blinded extension study (KINECT 3 extension; 77 mood participants) of valbenazine in adults with TD. Efficacy assessments included Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7), Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD), and Patient Global Impression of Change (PGIC). Safety assessments included treatment-emergent adverse events (TEAEs), Young Mania Rating Scale, and Montgomery-Åsberg Depression Rating Scale. RESULTS: At Week 6, mean improvements in AIMS total score were significantly greater with valbenazine versus placebo (40 mg/day, -3.1 [P < 0.01]; 80 mg/day, -3.5 [P < 0.001]; placebo, -0.9). Significant differences between valbenazine (80 mg/day) and placebo were also found for Week 6 AIMS response (≥50% total score improvement) and CGI-TD response ("much improved" or "very much improved"), but not PGIC response. Sustained improvements in AIMS, CGI-TD, and PGIC were found through 48 weeks. Valbenazine was generally well tolerated, with no unexpected TEAEs, worsening in psychiatric symptoms, or emergence of suicidality. LIMITATIONS: Pooled analyses were conducted post hoc, and neither study was designed to focus solely on mood disorder patients. CONCLUSIONS: In participants with primary mood disorders, once-daily treatment with valbenazine was generally well tolerated and resulted in 6-week and sustained TD improvements.


Assuntos
Transtornos do Humor/tratamento farmacológico , Discinesia Tardia/tratamento farmacológico , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Discinesia Tardia/induzido quimicamente , Discinesia Tardia/complicações , Tetrabenazina/efeitos adversos , Tetrabenazina/uso terapêutico , Valina/efeitos adversos , Valina/uso terapêutico
20.
Behav Brain Res ; 359: 942-949, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29935275

RESUMO

Psychological stresses such as social loss and separation during childhood induce hardship, referred to as emotional pain. These experiences are well-documented risk factors for the development of physical pain in adulthood. However, the underlying neuronal mechanisms of this exacerbation of pain are largely unknown, and consequently there is no effective pharmacotherapy. In this study, we sought to determine whether infant maternal separation (MS) contributes to aggravation of neuropathic pain in adult mice. MS increased anxiety- and depression-like behavioral responses to adult stress. In MS animals, chronic constriction injury (CCI) heightened the sensory dimension of chronic pain relative to that of control mice. However, MS mice treated with fluoxetine for 4 weeks after MS did not exhibit augmentation of allodynia, and their emotional response was attenuated. Microglia were more abundant in the spinal cord in MS/CCI mice than in control/CCI mice. These results suggest that emotional impairment is related to augmentation of neuropathic pain, and that dysfunction of microglial activation contributes to heightened pain sensitivity.


Assuntos
Privação Materna , Transtornos do Humor/etiologia , Neuralgia/complicações , Neuralgia/psicologia , Animais , Animais Recém-Nascidos , Antidepressivos de Segunda Geração/uso terapêutico , Proteínas de Ligação ao Cálcio , Modelos Animais de Doenças , Fluoxetina/uso terapêutico , Preferências Alimentares/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Proteínas dos Microfilamentos , Microglia/metabolismo , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/patologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Sacarose/administração & dosagem , Natação/psicologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA