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2.
J Opioid Manag ; 15(4): 342-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637686

RESUMO

A 49-year-old male with major depressive disorder well-managed with venlafaxine [serotonin and norepinephrine reuptake inhibitor (SNRI)] and no history of manic episodes developed his first manic episode following use of tramadol. Tramadol-induced mania has been described with selective serotonin reuptake inhibitors but not SNRIs. In addition, mania is not listed as a potential clinical side effect-further illustrating this relative rarity. Due to tramadol's SNRI activity, there is definitive risk for mood lability in individuals managed with tramadol and other serotonergic medications as seen in this patient. The authors findings suggest the need for greater risk consideration when prescribing tramadol with other related agents such as venlafaxine.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Tramadol , Cloridrato de Venlafaxina , Analgésicos Opioides , Transtorno Bipolar/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/efeitos adversos , Tramadol/efeitos adversos , Tramadol/uso terapêutico , Cloridrato de Venlafaxina/efeitos adversos , Cloridrato de Venlafaxina/uso terapêutico
3.
N Engl J Med ; 381(10): 903-911, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483961

RESUMO

BACKGROUND: Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS: In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse). RESULTS: A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was -17.4±1.3 points in the SAGE-217 group and -10.3±1.3 points in the placebo group (least-squares mean difference in change, -7.0 points; 95% confidence interval, -10.2 to -3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence. CONCLUSIONS: Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530.).


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Moduladores GABAérgicos/uso terapêutico , Receptores de GABA-A/metabolismo , Administração Oral , Adulto , Regulação Alostérica , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/classificação , Tontura/induzido quimicamente , Método Duplo-Cego , Feminino , Moduladores GABAérgicos/efeitos adversos , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Escalas de Graduação Psiquiátrica
4.
Psychiatr Danub ; 31(Suppl 3): 237-241, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488733

RESUMO

BACKGROUND: In a two-year study, we compared the efficacy of noradrenergic and serotonergic antidepressants with and without the addition of 100 mg acetylsalicylic acid (ASA) in subjects suffering from major depressive disorder (MDD). In this article we examine the influence of the health locus of control, family relationships and personality traits on the progress of MDD. SUBJECTS AND METHODS: 40 people with MDD (MDD group) were randomly assigned to the different treatment groups. They were followed in parallel with a group of 20 'healthy' subjects (HG). At the beginning of the study, sociodemographic data were collected, and patients were asked to complete the Multidimensional Health Locus of Control (MHLC) scale, the NEO Five-Factor Inventory (NEO-FFI), and the Family Adaptation and Cohesion Scale (FACES III). During the study subjects were regularly assessed using the Hamilton Depression Scale (HDS), the Short Form Health Survey (SF-12) and the Clinical Global Impression scale (CGI). RESULTS: Regardless of the type of treatment, physical health is the best predictor of variation at two years in the MDD group; 45% of variance is explained by a linear regression model that includes three variables from the MHLC, FACES III and NEO-FFI scales. Similarly, 40% of CGI and 24% of HDS variance is predicted. These explanatory variables are statistically less powerful in the MDD group than the HG group. CONCLUSION: While drug treatment is a determinant in changes on the HDS, CGI and SF12 scales, factors such as family relationships, MHLC or personality are important covariates of these changes. The question remains whether we can influence these covariates to improve the response to antidepressants.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Relações Familiares , Controle Interno-Externo , Humanos , Escalas de Graduação Psiquiátrica
5.
Psychiatr Danub ; 31(Suppl 3): 252-257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488736

RESUMO

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


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/imunologia , Ketamina/imunologia , Ketamina/uso terapêutico , Antidepressivos/imunologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/imunologia , Humanos , Imunomodulação/imunologia
6.
Psychiatr Danub ; 31(Suppl 3): 258-260, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488737

RESUMO

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


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Suicídio/prevenção & controle , Depressão/tratamento farmacológico , Depressão/psicologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Humanos , Ideação Suicida , Suicídio/psicologia
7.
Psychiatr Danub ; 31(Suppl 3): 520-523, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488784

RESUMO

Major depressive disorder is one of the most important psychiatric issues worldwide, with important prevalence of treatment-resistant depression (TRD). Non-monoaminergic agents are currently in the spotlight. Objective was to explore for information about mechanisms of action of ketamine, its connections with copper and possible importance for TRD treatment. There are at least few possible pathways for ketamine action in depression in which copper and other divalent ions may show a vital role. There is urgent need for more studies to gather information about correlation between ketamine, copper and antidepressive features of these agents.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Cobre/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Ketamina/farmacologia , Ketamina/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/metabolismo , Humanos
8.
Psychiatr Danub ; 31(Suppl 3): 530-533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488786

RESUMO

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


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Depressão/tratamento farmacológico , Humanos , Qualidade de Vida
9.
Lancet Psychiatry ; 6(9): 735-744, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31371212

RESUMO

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


Assuntos
Terapia Cognitivo-Comportamental/métodos , Terapia Combinada/métodos , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Fluoxetina/uso terapêutico , Adolescente , Adulto , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Ansiedade/terapia , Austrália/epidemiologia , Comorbidade , Depressão/terapia , Transtorno Depressivo Maior/terapia , Método Duplo-Cego , Feminino , Fluoxetina/administração & dosagem , Humanos , Masculino , Inibidores de Captação de Serotonina/uso terapêutico , Ideação Suicida , Resultado do Tratamento , Adulto Jovem
10.
Expert Opin Drug Saf ; 18(10): 949-963, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430189

RESUMO

Introduction: Depression affects 300 million individuals worldwide. While selective serotonin reuptake inhibitors (SSRI) are one of the first-line pharmacological treatments of major depression in the general population, there is still uncertainty regarding their potential benefits and risks during pregnancy. Areas covered: Outcomes requisite for a proper risk/benefit assessment of SSRI in pregnancy and lactation were considered: (a) potential risks associated with untreated depression, (b) effectiveness of different treatment options of depression, (c) potential risks associated with SSRI. Expert opinion: Despite the growing amount of literature on SSRI use during pregnancy, no new trials assessing the benefits of SSRIs on maternal depression were found. In the light of new data regarding the potential risks, depressed SSRI-treated pregnant women and their children seem at increased risk for several complications (mostly of small absolute risk). The interpretation of these findings remains quite similar to our previous review as the available methodology does not allow to disentangle the potential effect of SSRIs from those of the disease itself or/and of its unmeasured associated risk factors. Thus, in pregnant or lactating women who require a pharmacological treatment, SSRIs can still be considered as appropriate when effective as the abundant data support their relative safety.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Feminino , Humanos , Recém-Nascido , Lactação/efeitos dos fármacos , Gravidez , Medição de Risco , Inibidores de Captação de Serotonina/efeitos adversos
11.
Medicine (Baltimore) ; 98(35): e16854, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464912

RESUMO

INTRODUCTION: Major depressive disorder (MDD) is a common condition worldwide, and leads to degradation in quality of life and large socioeconomic costs. There has been increasing demand for new therapies with fewer side effects. SOCG (SOCG tablet) is a modified prescription of So-ochim-tang, which is widely used in Traditional Korean Medicine to treat MDD. We aim to evaluate the efficacy of SOCG in treating MDD, and identify the optimum dose. DESIGN: The protocol we are following is that of a Phase II clinical trial with a randomized, double blinded, placebo controlled, and parallel design. One hundred forty-eight participants will be randomly divided into 4 groups and treated for 8 weeks. OUTCOME MEASURES: The primary outcome will be the score in the Korean Version of the Hamilton Depression Rating Scale. Scores in the Korean version of the Beck Depression Inventory-II Korean Symptom Check List-95 (KSCL-95), State Trait Anxiety Inventory-Korean version, State- Trait Anger Expression Inventory- Korean version (STAXI-K), Insomnia Severity Index (ISI), and the EuroQol-5 Dimension (EQ-5D) will be considered as secondary outcomes. DISCUSSION AND CONCLUSIONS: Demonstration of human safety and efficacy of SOCG in the present trial and identification of the appropriate dose will justify a New Drug Application and a phase III clinical trial. Further, we expect that this new antidepressant will be able to increase cure rates, and alleviate the burden of medical expenses. TRIAL REGISTRATION NUMBER: Clinical Research Information Service, Republic of Korea (KCT0002763).


Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Administração Oral , Adulto , Antidepressivos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Medicina Tradicional Coreana , Pessoa de Meia-Idade , Cooperação do Paciente , Extratos Vegetais/efeitos adversos , Qualidade de Vida , Projetos de Pesquisa , Comprimidos , Resultado do Tratamento , Adulto Jovem
12.
JAMA ; 322(7): 622-631, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429896

RESUMO

Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Olanzapina/uso terapêutico , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Modelos de Riscos Proporcionais , Prevenção Secundária , Sertralina/uso terapêutico , Adulto Jovem
13.
Lancet Psychiatry ; 6(9): 745-752, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31303567

RESUMO

BACKGROUND: Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data. METHOD: In this item-based, patient-level, post-hoc analysis, we pooled data from all completed, acute-phase, placebo-controlled, industry-sponsored, HDRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression. Patient-level data were pooled and subjected to item-based post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score, the depressed mood item of the HDRS, a six-item HDRS subscale (HDRS-6), and the remaining 11 HDRS items not included in this subscale (non-HDRS-6). Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more. FINDINGS: Our study population consisted of 8262 patients from 28 placebo-controlled SSRI trials. Participants were treated with either citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine (active-control group; n=754), or placebo (n=2581). 654 patients were defined as having non-severe depression and 1377 as having severe depression. Patients with non-severe and severe depression did not differ with respect to SSRI-induced decrease in depressed mood and other HDRS symptoms belonging to the HDRS-6 subscale. However, after exclusion of patients with rare extreme baseline values, a positive association was seen between severity and efficacy when using HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression than in those with non-severe depression. This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression. INTERPRETATION: The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients. With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression. FUNDING: Swedish Medical Research Council, AFA Insurance, Swedish Brain Foundation, Sahlgrenska University Hospital (Avtal om Läkarutbildning och Forskning), Bertil Hållsten's Foundation, and Söderberg's Foundation.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Citalopram/administração & dosagem , Citalopram/uso terapêutico , Ensaios Clínicos como Assunto , Depressão/psicologia , Transtorno Depressivo Maior/psicologia , Fluoxetina/administração & dosagem , Fluoxetina/uso terapêutico , Humanos , Estudos Longitudinais , Avaliação de Resultados (Cuidados de Saúde) , Paroxetina/administração & dosagem , Paroxetina/uso terapêutico , Placebos/administração & dosagem , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Reprodutibilidade dos Testes , Inibidores de Captação de Serotonina/administração & dosagem , Sertralina/administração & dosagem , Sertralina/uso terapêutico , Índice de Gravidade de Doença
14.
BMC Neurol ; 19(1): 174, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31325958

RESUMO

BACKGROUND: Tardive dyskinesia (TD) is a serious, often irreversible movement disorder caused by prolonged exposure to antipsychotics; identifying patients at risk for TD is critical to preventing it. Predictive models for the occurrence of TD can improve patient monitoring and inform implementation of counteractive interventions. This study aims to identify risk factors associated with TD and to develop a model using a retrospective data analysis to predict the incidence of TD among patients taking antipsychotic medications. METHODS: Adult patients with schizophrenia, major depressive disorder, or bipolar disorder taking oral antipsychotics were identified in a Medicaid claims database (covering six US states from 1997 to 2016) and divided into cohorts based on whether they developed TD within 1 year after the first observed claim for antipsychotics. Patient characteristics between cohorts were compared, and univariate Cox analyses were used to identify potential TD risk factors. A cross-validated version of the least absolute shrinkage and selection operator regression method was used to develop a parsimonious multivariable Cox proportional hazards model to predict diagnosis of TD. RESULTS: A total of 189,415 eligible patients were identified. Potential TD risk factors were identified based on the cohort analysis within a sample of 151,280 patients with at least 1 year of continuous eligibility. The prediction model had a clinically meaningful concordance of 70% and was well calibrated (P = 0.32 for Hosmer-Lemeshow goodness-of-fit test). Age (hazard ratio [HR] = 1.04, P < 0.001), diagnosis of schizophrenia (HR = 1.99, P < 0.001), antipsychotic dosage (up to 100 mg/day chlorpromazine equivalent; HR = 1.65, P < 0.01), and comorbid bipolar and related disorders (HR = 1.39, P < 0.01) were significantly associated with an increased risk of TD. Other potential risk factors included history of extrapyramidal symptoms (HR = 1.35), other movement disorders (parkinsonism, HR = 1.43; bradykinesia, HR = 1.44; tremors, HR = 2.12, and myoclonus, HR = 2.33), and diabetes (HR = 1.13). A modest reduction in the risk of TD was associated with the use of second-generation antipsychotics (HR = 0.85) versus first-generation drugs. CONCLUSIONS: This study identified factors associated with development of TD among patients taking antipsychotics. The prediction model described herein can enable physicians to better monitor patients at high risk for TD and recommend appropriate treatment plans to help maintain quality of life.


Assuntos
Antipsicóticos/efeitos adversos , Discinesia Tardia/induzido quimicamente , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Esquizofrenia/tratamento farmacológico
15.
Drugs Today (Barc) ; 55(7): 423-437, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31347611

RESUMO

Depression is a neuropsychiatric disorder that affects more than 350 million people all over the world. There are psychological and pharmacological treatments for depression which mainly focus on monoaminergic neurotransmission theory. The main concern regarding available antidepressants is the lag period and other side effects, such as sexual dysfunction. Gepirone is a drug of the azapirone group which is a 5-HT1A receptor agonist belonging to the buspirone family. Gepirone is under clinical development and has been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs), as this drug treats the psychiatric disorders without causing sexual dysfunction, which limits the use of SSRIs. It possesses greater selectivity for the 5-HT1A receptor than SSRIs. Clinical studies have shown that gepirone has differential action at pre- and postsynaptic 5-HT1A receptors. Gepirone extended-release tablets (gepirone ER, Travivo) showed promising effects in adult outpatients for the treatment of major depressive disorder (MDD) in a double-blind, randomized, placebo-controlled clinical study. Gepirone also showed an antianxiety effect in a placebo-controlled trial in generalized anxiety disorder. Absorption of gepirone is increased when administered with food as there is no substantial change in Cmax and half-life but it significantly increases AUC and mean residence time. Gepirone undergoes first-pass metabolism and its major metabolites are 1- (2-pyrimidinyl)-piperazine (1-PP) and 3-OH-gepirone, both of which are pharmacologically active. In addition to its better efficacy, gepirone is well tolerated and the major adverse effects observed have been nausea, dizziness and lightheadedness. Evidence from preclinical and clinical studies revealed that gepirone could be a breakthrough therapeutic agent in the treatment of anxiety and MDD.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Pirimidinas/uso terapêutico , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Expert Opin Pharmacother ; 20(14): 1743-1754, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31290333

RESUMO

Introduction: Persistent Depressive Disorder (PDD) is a nosological entity introduced with DSM-5, encompassing numerous different conditions including Dysthymia, recurrent Major Depressive Disorder, Double Depression and Chronic Major Depression. PDD is a particularly significant cause of disease burden in the general population. Areas covered: In the present paper, the authors explore the controversies surrounding the definition of PDD, the current approach to its treatment endorsed by the major scientific bodies, along with the available evidence on the efficacy of said treatments. Expert opinion: Clinicians need to be particularly vigilant and always gather a thorough history. In this diagnostic group, there is a relevant risk of having an undiagnosed Bipolar Disorder as affected individuals typically fail to recognize the pathological components of hypomanic episodes. In this setting, it is crucial to reconsider the diagnosis and to frequently verify compliance with the treatment plan. Numerous technological advances, particularly in the neuroimaging field, offer new insight and new challenges in defining the pathophysiological mechanisms of depressive syndromes. In the future, these advances may offer guidance towards an improved treatment approach and diagnostic process.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Distímico/tratamento farmacológico , Amissulprida/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/patologia , Transtorno Distímico/patologia , Humanos , Psicoterapia , Qualidade de Vida , Resultado do Tratamento
17.
Artigo em Russo | MEDLINE | ID: mdl-31317905

RESUMO

Agomelatine is an antidepressant agent with an innovative unique pharmacodynamic profile, including melatonergic receptor agonism (MT1 / MT2) and antagonistic effects on serotonergic 5-HT2C receptors. According to the results of meta-analyzes of clinical studies of the acute phase of a major depressive disorder, the antidepressant effect of agomelatine itself is significantly higher than that of placebo, but somewhat inferior to a number of other antidepressants (especially SSRIs and venlafaxine). To date, there is some uncertainty regarding the efficacy of agomelatine for the prevention of recurrence of MDD and its hepatotoxicity profile. In this regard, agomelatine is not considered as a drug of first choice in treatment of MDD. However, the heterogeneous clinical manifestations of MDD and the unique mechanism of action of agomelatine with the ability of the drug to have a modulating effect on sleep, make it possible to effective use it for treating such disorders. In addition, agomelatine has a more favorable safety profile, which allows considering it as a drug of choice in patients who have contraindications to other antidepressants or in the absence of therapeutic response to another antidepressant therapy.


Assuntos
Acetamidas , Antidepressivos , Transtorno Depressivo Maior , Acetamidas/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Inibidores de Captação de Serotonina
18.
Expert Opin Pharmacother ; 20(15): 1907-1916, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31290344

RESUMO

Background: There is a need for effective, safe and well-tolerated pharmacotherapies for patients with major depressive disorder (MDD) who have inadequate response to antidepressant treatments (ADTs). This analysis aimed to summarize the short-term efficacy and safety of adjunctive brexpiprazole in adults with MDD. Research design and methods: A pooled analysis of data from the 6-week, randomized, double-blind treatment phases of four studies of adjunctive brexpiprazole 1-3 mg/day versus placebo in outpatients with MDD and inadequate response to ADTs (n = 1,853). Efficacy was measured by Montgomery-Åsberg Depression Rating Scale (MADRS) scores, and safety by treatment-emergent adverse events (TEAEs). Results: ADT + brexpiprazole 2-3 mg/day showed greater improvement in MADRS Total score from baseline to Week 6 than ADT + placebo (least squares mean difference: -2.15; confidence limits: -2.82, -1.48; p < 0.0001; Cohen's d effect size: 0.33). TEAEs with incidence ≥5% with ADT + brexpiprazole 1-3 mg/day were akathisia (8.0% versus 2.6% with ADT + placebo), headache (5.8% versus 6.0%), and weight increased (5.8% versus 1.6%). Conclusions: Adjunctive brexpiprazole is an efficacious and well-tolerated treatment option for adult patients with MDD and inadequate response to ADTs. Study limitations included a lack of active comparator.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Quinolonas/uso terapêutico , Tiofenos/uso terapêutico , Adulto , Antidepressivos/farmacologia , Transtorno Depressivo Maior/patologia , Feminino , Humanos , Masculino , Quinolonas/farmacologia , Tiofenos/farmacologia , Resultado do Tratamento
19.
Lancet Psychiatry ; 6(7): 601-609, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31178367

RESUMO

BACKGROUND: Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question. METHODS: We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4-12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine. FINDINGS: 28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses. INTERPRETATION: For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression. FUNDING: Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Mirtazapina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Cloridrato de Venlafaxina/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Serotoninérgicos/uso terapêutico
20.
Expert Opin Ther Pat ; 29(7): 497-507, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31242055

RESUMO

INTRODUCTION: Positive allosteric modulation of mGlu2 has attracted much interest as an alternative approach to classical orthosteric receptor activation. Two mGlu2 PAMS have advanced into the clinic. The results obtained in schizophrenia and MDD phase 2 clinical trials have tempered the high expectations put on selective mGlu2 receptor activation for treating these conditions; nevertheless, the search for novel therapeutic indications and novel chemotypes continues to be an active field of research. AREAS COVERED: 2013-2018 patent literature on mGlu2 receptor PAMs. EXPERT OPINION: After a decade of intensive research, the mGlu2 PAM field has seen a deceleration in the last five years. Negative phase 2 schizophrenia clinical trials with JNJ-40411813 and AZD8529 seem to have tempered the high expectations of the scientific community on the utility of mGlu2 PAMs for the treatment of schizophrenia. Nevertheless, novel therapeutic indications continue to be explored and AZD8529 is currently in a phase 2 study for smoking cessation. The advances in medicinal chemistry and in pharmacology, with novel indications such as epilepsy, have set the stage in the field of mGlu2 receptor PAMs. Ongoing preclinical and clinical studies will contribute to define their optimal therapeutic indication and potential to become novel therapeutic agents.


Assuntos
Indóis/uso terapêutico , Oxidiazóis/uso terapêutico , Piperidinas/uso terapêutico , Piridonas/uso terapêutico , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Regulação Alostérica/efeitos dos fármacos , Animais , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Humanos , Indóis/farmacologia , Oxidiazóis/farmacologia , Patentes como Assunto , Piperidinas/farmacologia , Piridonas/farmacologia , Receptores de Glutamato Metabotrópico/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia
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