Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25.659
Filtrar
1.
Medicine (Baltimore) ; 98(41): e17501, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593119

RESUMO

BACKGROUND: Traditional treatment of functional dyspepsia (FD) is unsatisfactory in a subgroup of patients with FD, and the potential role of antidepressant medications also has not been definitely clarified. To provide more evidence for future optimal practice recommendations, we reviewed a 1-year clinical database of antidepressant agents applied in outpatients with FD. METHODS: Clinical presentations, treatment course, and outcomes were determined by chart review of patients referring to the functional gastrointestinal disorders specialist clinic. One hundred thirty patients with FD were included for further analysis. RESULTS: Patients were treated with different antidepressant drugs according to individual symptoms. The most commonly used drugs were flupenthixol melitracen and fluoxetine. Improvement and complete remission occurred in 93.8% and 54.6% of patients, respectively. There was a trend toward superior outcome for citalopram compared to sulpiride and mirtazapine in overall analysis. Meanwhile, regimens containing fluoxetine had significant increased remission rate compared to any other antidepressant regimens in postprandial distress syndrome subgroup analysis. Furthermore, older patients were more likely to achieve remission. However, sex and symptom duration were not associated with symptom remission. Finally, 11.5% of patients experienced adverse events. CONCLUSIONS: This retrospective cohort study indicated that small dose antidepressant therapy, especially citalopram and fluoxetine, is an effective and well tolerated treatment option for refractory FD.


Assuntos
Antracenos/uso terapêutico , Dispepsia/tratamento farmacológico , Fluoxetina/uso terapêutico , Flupentixol/uso terapêutico , Antracenos/efeitos adversos , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , China/epidemiologia , Citalopram/uso terapêutico , Combinação de Medicamentos , Dispepsia/diagnóstico , Feminino , Fluoxetina/efeitos adversos , Flupentixol/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Período Pós-Prandial , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
2.
Adv Mind Body Med ; 33(3): 22-30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31605602

RESUMO

Background: A 38-year-old, female with a history of GAD, MDD, AN, and PTSD wanted to taper her multiple medications in preparation for pregnancy. Benzodiazepine medications, such as Klonopin and Restoril; antidepressants, such as Effexor; and anticonvulsant medications, such as Lamictal, can be habit-forming, and withdrawal symptoms can occur upon discontinuation of use. Polypharmacy can be implicated in poor clinical outcomes, and a strategic and supported medication taper may improve those outcomes. Summary: After the primary MD unsuccessfully attempted to taper off the patient's psychotropic medications without lifestyle interventions, she was stabilized on a minimal regimen by an outside reproductive psychiatrist throughout her pregnancy. A second tapering was implemented by the primary MD after the patient had given birth and had established changes to her lifestyle. These lifestyle interventions included dietary changes, use of detoxification protocols, contemplative practices, and strategic supplement support in the setting of a powerful mindset shift. The patient experienced remarkable symptom remission after strategic discontinuation of medications through the addition of the lifestyle interventions. She also was able to heal the root-cause drivers of her psychiatric diagnoses. Currently she is symptom-free and medication-free after nearly 21 years. Conclusions: This case demonstrates the effectiveness of lifestyle interventions and psychospiritual support to enable dramatic clinical change without withdrawal syndrome after cessation of medication. More important, the initial failed tapering underpins the notion that a diligent meditation practice may be necessary to heal root-cause drivers of psychiatric symptoms and withdrawal syndrome. The results may serve to inform practitioners assisting patients who wish to discontinue benzodiazepine and other psychotropic medications or patients who would like to try a nonpharmaceutical approach as a first-line therapy.


Assuntos
Antidepressivos/efeitos adversos , Estilo de Vida , Psicotrópicos/efeitos adversos , Síndrome de Abstinência a Substâncias , Adulto , Antidepressivos/uso terapêutico , Benzodiazepinas , Feminino , Humanos , Psicotrópicos/uso terapêutico , Síndrome de Abstinência a Substâncias/etiologia
4.
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
5.
Postgrad Med ; 131(7): 438-444, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31482756

RESUMO

Pain is a subjective experience that is influenced by genetics, gender, social, cultural and personal parameters. Opposed to chronic pain, which by definition has to last for at least 3 months, acute pain is mostly because of trauma, acute medical conditions or treatment. The link between mood disorders and acute pain has proven to be increasingly significant since the link is bi-directional, and both act as risk factors for each other. Depression and anxiety are associated with increased perception of pain severity, whereas prolonged duration of acute pain leads to increased mood dysregulation. Although both depression and anxiety have a proven association with acute pain, the link between depression and acute pain is more thoroughly studied. Pain can be the presenting or sole complaint in depressed patients who present to primary care practices and is often overlooked by clinicians. However, reports on the perception of experimentally-induced pain in depressed patients are mixed, showing both an increased and decreased pain threshold and pain tolerance across various studies. Although less data is published about anxiety and pain, the relationship is consistent across studies as increased anxiety leads to increased severity of pain perceived and decreased pain tolerance. Anxiety as well as fear, stress, and catastrophizing are also shown to be mediators in the causal pathway between pain and disability.


Assuntos
Dor Aguda/psicologia , Transtornos de Ansiedade/psicologia , Transtorno Depressivo/psicologia , Dor Aguda/epidemiologia , Dor Aguda/fisiopatologia , Dor Aguda/terapia , Analgésicos/uso terapêutico , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/terapia , Catastrofização/epidemiologia , Catastrofização/fisiopatologia , Catastrofização/psicologia , Terapia Cognitivo-Comportamental , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/terapia , Humanos , Manejo da Dor , Limiar da Dor , Índice de Gravidade de Doença
6.
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
7.
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
8.
Psychiatr Danub ; 31(Suppl 3): 411-415, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488762

RESUMO

BACKGROUND: Based on our 2012 study and a review of the literature on the therapeutic alliance we asked ourselves different questions: does the alliance exert a real influence on the evolution of depressive affects, the rate of remission and the physical and global health? SUBJECTS AND METHODS: In a two-year study, forty people with major depressive disorder are randomly assigned to groups that receive a SSRI (escitalopram) or a SNRI (duloxetine), each group receive concomitant ASA (100 mg) or a placebo. Sociodemographic data are recorded and patients under went regular assessments with the Hamilton depression scale (HDS) and Clinical Global Impression (CGI) scale, the Helping Alliance Questionnaire (HAQ) and the Short Form Health Survey (SF-12). RESULTS: There is no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA. However, subgroup comparisons reveal that the duloxetine + ASA (DASA) subgroup showed a more rapid improvement in HDS score as early as 2 months (t=-3.114, p=0.01), in CGI score at 5 months (t=-2.119, p 0.05) than the escitalopram + placebo (EP) subgroup. Regardless of the treatment arm, the remission rate at 2 years is 50%. Among patients in remission a majority, 65%, have a high level of alliance in opposition to nonresponders who have found mostly a low level of alliance (χ2=6.296, p 0.012). HAQ scores are not correlated with HAD scores, but a correlation is found with remission rates (r=0.316*). At all times, HAQ scores are correlated with physical health. CONCLUSION: Our findings suggest that a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone. A good alliance improves effectiveness of anti-depressant treatment of 1.85 and leads to an improvement of the physical health rather than directly on the depressive feelings.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/terapia , Nível de Saúde , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Aliança Terapêutica , Citalopram/uso terapêutico , Método Duplo-Cego , Cloridrato de Duloxetina/uso terapêutico , Humanos
9.
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
10.
Psychiatr Danub ; 31(Suppl 3): 549-553, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488789

RESUMO

Depression affects over 121 million people annually worldwide. Relatively low remission rates among depressive patients enforce the search for new therapeutic solutions and an urgent need to develop faster-acting antidepressants with a different mechanism of action occurs. The pathomechanism of depression postulated by the monoamine hypothesis is limited. The results of abnormalities in glutamate and γ-aminobutyric acid (GABA) systems in the brains of people with mood disorders allowed to develop new theories regarding pathophysiology of these disorders. Glutamatergic transmission is influenced by magnesium and ketamine through glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonistic effects. Magnesium and ketamine have a common mechanism of action in the treatment of depression: an increase in GluN2B (NMDAR subunit) expression is related to the administration of both of the agents, as well as inhibition of phosphorylation of eEF2 (eukaryotic elongation factor 2) in cell culture and increase of the expression of BDNF in the hippocampus. Combination of ketamine and magnesium in a normal magnesium level presents a superadditive effect in depression treatment. Analysed substances affect the GABAergic system and have anti-inflammatory effects, which is correlated with their antidepressant effect. The synergistic interaction between the pharmacodynamic activity of magnesium and ketamine may be of particular importance for patients with mood disorders. Further research is needed to determine the relationship between magnesium levels and ketamine treatment response mainly in the attempt to establish if the magnesium supplementation can change ketamine treatment response time or present superadditive effect.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Ketamina/uso terapêutico , Magnésio/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Humanos , Fator 2 de Elongação de Peptídeos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
11.
Psychiatr Danub ; 31(Suppl 3): 554-560, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488790

RESUMO

Bipolar depression (BD) is among the most severe psychiatric disorders. A significant number of patients do not achieve an entirely symptom-free state and experience residual sub-syndromal depression. Most of the treatment options approved for bipolar depression give no rapid symptom improvement. Ketamine is an anaesthetic medication that acts as an antagonist of the NMDA receptor and has antidepressant potential. Due to its unique way of action, ketamine seems to be crucial for the treatment of anhedonia. This review paper aims to provide an overview of the efficacy of ketamine infusions in bipolar depression with a focus on anhedonia Literature suggests that intravenous ketamine 0.5 mg/kg over 40 min weekly could be useful in the treatment of bipolar depression with prominent anhedonia, but there is still a small number of studies that examine the efficacy of ketamine infusions in BD. In conclusion, ketamine should be considered as a valuable treatment option for patients with BD and anhedonia.


Assuntos
Anedonia/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Depressão/complicações , Depressão/tratamento farmacológico , Ketamina/farmacologia , Ketamina/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Bipolar/complicações , Humanos
12.
Psychiatr Danub ; 31(Suppl 3): 585-590, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488795

RESUMO

Ketamine is an anaesthetic and analgesic agent that demonstrates the antidepressive effect in major depression. Several administrations routes, dosing schemas and esketamine are investigated in basic and clinical research with particular focus on treatment-resistant depression (TRD) where drug demonstrates its efficacy where very limited alternatives are available. The majority of ketamine studies in TRD treatment reported no serious adverse events regardless the administration route or regimen. However, the most commonly observed adverse events following ketamine administration in antidepressive doses include general, psychotomimetic, dissociative and hemodynamic ones. The side effects are mild or moderate, well-tolerated and transient. This paper discusses the risks regarding cardiovascular safety in MDD patients in short-term ketamine administration with particular focus on the effect on blood pressure and adverse drug reactions mitigation measures. The increase in systolic (SBP) and diastolic (DBP) blood pressure is dose-dependent and begins shortly after administration peaking at around 30 to 50 minutes with SBP and DBP rise from 10% to 50% above predose values and resolving at approximately 2 to 4 hours after the dose administration. These changes generally are primarily asymptomatic. The elevations in SBP and DBP are observed on each dosing day with multiple administration schema. The treatment with ketamine and esketamine is contradicted in subjects at risk of an increase in blood pressure or intracranial pressure. The current evidence indicates the blood pressure should be assessed prior to dosing with ketamine and hypertensive individuals shall receive effective lifestyle/pharmacologic management prior to treatment. Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains elevated acute blood pressure management shall be delivered. In patients experiencing symptoms of hypertensive crisis immediate emergency care must be provided. The unmet need for improved pharmacotherapies for TRD means the use of ketamine and esketamine is warranted therapeutic option in patients who fail to achieve a sustained remission of depressive symptoms with drugs with monoamine-based mechanisms of action. Adequate safety measures must be applied when using ketamine/esketamine in TRD subjects with particular focus on somatic comorbidities as the transient drug effect on cardiovascular system is demonstrated and of clinical significance.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Depressão/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
13.
Tijdschr Psychiatr ; 61(7): 498-503, 2019.
Artigo em Holandês | MEDLINE | ID: mdl-31372971

RESUMO

Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.


Assuntos
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Lítio/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Antidepressivos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
Expert Opin Drug Saf ; 18(10): 893-913, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364895

RESUMO

Introduction: The use of antidepressants (AD) in the treatment of bipolar depression is one of the most controversial issues in psychopharmacology. For some, AD are useful, but, for others, they should never be used in bipolar depression. Areas covered: This review examines published clinical studies on the use of ADs in bipolar depression, addressing their clinical efficacy and the occurrence of side effects, manic switches, cycle acceleration, and suicidal behavior. Meta-analyzes and review articles on the subject are also discussed. Expert opinion: Approved therapeutic options for bipolar depression are associated with not very high response rates and a high incidence of adverse effects. Patients with bipolar depression present very heterogeneous responses to the use of ADs. Some improve significantly, while others, especially those with concomitant manic symptoms, have had previous episodes of treatment-emergent mania or are rapid cyclers, exhibit manic switches or cycle acceleration. The authors conclude that the real question is not whether ADs should or should not be used in bipolar depression, but which patients benefit from these drugs and which ones are impaired. The concept of bipolar spectrum and a dimensional approach on bipolar/unipolar distinction may be useful for understanding the heterogeneity of responses to ADs.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Seleção de Pacientes , Antidepressivos/efeitos adversos , Transtorno Bipolar/fisiopatologia , Humanos , Resultado do Tratamento
15.
Medicine (Baltimore) ; 98(31): e16674, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374046

RESUMO

BACKGROUND AND OBJECTIVE: A recent striking advance in the treatment of depression has been the finding of rapid antidepressant effects in over 70% of patients with treatment-resistant depression (TRD) using ketamine. However, the potential risk of addiction may limit its clinical use. Recent research revealed that blockade of N-methyl-D-aspartate receptor (NMDAR) dependent bursting activity in the lateral habenula (LHb) could mediate the fast antidepressant effects of ketamine. Further, LHb bursting plays an important role in the pathophysiology of depression that requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Ethosuximide, which is used to treat absence seizures, is a T-VSCCs inhibitor, may be a novel drug candidate for depression. The objective of this clinical trial is to investigate the efficacy and safety of ethosuximide in patients with TRD. DESIGN: The study is a single center, randomized, double-blind, placebo-controlled, parallel-group, two-stage clinical trial. Forty patients with TRD will be randomly assigned to Group A (treatment group) or Group B (control group). In the first stage ethosuximide or placebo will be given for 2 weeks. In the second stage, escitalopram (or another antidepressant if escitalopram has been used before) will be given for the next 4 weeks for all trial patients to ensure effective treatment. The primary outcome measure is the Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcome measures include the Quick Inventory of Depressive Symptomatology-Self Report score, Hamilton Anxiety Rating Scale scores, individual scores of MADRS, and Young Mania Rating Scale scores. All these scales are measured at baseline and at each treatment visit. Two-way repeated measures analysis of variance is used to analyze the study outcomes. DISCUSSION: A statistical analysis plan is employed to enhance the transparency of the clinical trial and reduce the risks of outcome reporting bias and data-driven results.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Etossuximida/uso terapêutico , Método Duplo-Cego , Etossuximida/farmacologia , Humanos , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Artigo em Russo | MEDLINE | ID: mdl-31464295

RESUMO

The authors discuss the relationship between depression and cognitive impairment in the aspect of mechanisms of their development, variants of comorbidity and recommendations on differentiated therapy in elderly. The diagnostic differentiation between depression and dementia at different stages of dementia as well as in younger and older ages, a role of depression as a risk factor for dementia, a role of other factors, in particular age, as well as treatment approaches on the example of antidepressants and cerebrolysin are considered.


Assuntos
Disfunção Cognitiva , Demência , Depressão , Transtorno Depressivo , Idoso , Antidepressivos/uso terapêutico , Disfunção Cognitiva/complicações , Depressão/complicações , Depressão/tratamento farmacológico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Humanos , Pessoa de Meia-Idade
18.
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
19.
Artigo em Russo | MEDLINE | ID: mdl-31317892

RESUMO

AIM: Comparative evaluation of the efficacy and safety of antidepressant monotherapy and complex antidepressant therapy in combination with carnicetine in the treatment of depression in elderly patients in a psychiatric hospital. MATERIAL AND METHODS: Two groups of hospitalized patients, aged from 60 to 79 years, with mild or moderate depression (according to ICD-10), comparable in basic demographic and clinical characteristics, received mono- or complex (in combination with carnicetine) antidepressant therapy for 8 weeks. Treatment efficacy was assessed with HAM-D, HARS, CGI-S and CGI-I; the level of cognitive activity was assessed with MMSE, the 10-word memory test and clock drawing test. RESULTS: It has been established that the use of complex antidepressants therapy with the inclusion of carnicetine allows to achieve a more rapid and pronounced therapeutic response compared to antidepressant monotherapy. This is confirmed by the earlier (by the 4th week) and significant reduction of depressive and anxiety symptoms (p<0.01), a greater number of responders and better quality of depressive outcomes to the end of treatment and a more rapid improvement in cognitive functioning. CONCLUSION: The results allow us to recommend the inclusion of carnicetine for the augmentation of antidepressant therapy in elderly patients of the psychiatric hospital to achieve a more rapid and complete therapeutic response and reduce the duration of hospitalization.


Assuntos
Antidepressivos , Transtorno Depressivo , Idoso , Antidepressivos/uso terapêutico , Ansiedade , Transtorno Depressivo/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA