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1.
Medicina (Kaunas) ; 56(2)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050466

RESUMO

The current psychopharmacological treatment approaches for major depression focus on monoaminergic interventions, which are ineffective in a large proportion of patients. Globally, treatment-resistant bipolar depression (TRBD) affects up to 33% of depressive patients receiving treatment. Certain needs are still unmet and require new approaches. Many studies are in favor of treatments with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, even in single use, whose effects emerge in minutes to hours post administration. However, little data are available on ketamine performance in TRBD patients with somatic comorbidities, including highly prevalent ones, i.e., cardiovascular disease (heart failure, hypertension, post-myocardial infarct, arrhythmias, etc.) diabetes, and obesity, and depression-associated comorbidities such as stroke, epilepsy, as well as in the elderly population. The literature shows that treatment with ketamine is efficacious and safe, and the majority of adverse drug reactions are mild and tend to mostly disappear within 30 min to 2 h of ketamine administration.

3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
Epileptic Disord ; 20(6): 562, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30530406

Assuntos
Neurossífilis , Humanos
12.
Med Hypotheses ; 118: 74-77, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30037619

RESUMO

Schizophrenia is a mental disorder that mostly appears in the second or third decade of life with no consistent appearance. The first-line pharmacological treatment are antipsychotic drugs, which mainly act by suppressing the activity of dopamine. Unfortunately many of schizophrenic patients suffer from persistent positive or negative symptoms that cannot be fully treated with available medication. With exploration on the possible causes of the disease there is evidence on dopaminergic transmission defects, there is a need to find more holistic way in treating the disease and a diet regimen could be one of them. Ketogenic diet, which is a popular diet regimen that consists in low-carbohydrate (about 30-50 g/day), medium-protein (up to 1 g/kg daily) and high-fat intake (around 80% of daily calories) mainly known for its helpful role in weight-loss. The key mechanism is to generate ketosis. A state in which ketones bodies in the blood provides energy part of the body's energy comes from ketone bodies in the blood. Possible hypothesis can be that ketogenic diet changes the ratio of GABA:glutamate in favor of GABA, by suppressing the catabolism and increasing the synthesis of GABA as well as glutamate metabolism, which could help to compensate the disrupted GABA levels in schizophrenic brain, leading to possible better outcome of the disease regarding symptomatology and preventing the weight-gain regarding some medications used and the correlating diseases responsible for weight gain.


Assuntos
Dieta Cetogênica , Gorduras na Dieta/administração & dosagem , Ingestão de Energia , Metabolismo Energético , Corpos Cetônicos/metabolismo , Esquizofrenia/dietoterapia , Antipsicóticos/uso terapêutico , Encéfalo/metabolismo , Dieta , Jejum , Ácido Glutâmico/metabolismo , Humanos , Cetose , Modelos Teóricos
16.
Psychiatr Danub ; 29(Suppl 3): 341-344, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953787

RESUMO

BACKGROUND: Neurosyphilis is an infection of the brain or spinal cord caused by Treponema pallidum. In the third phase of syphilis involving the central nervous system it may manifest in a widespread dysfunctions including psychiatric manifestations being often underestimated in the differential diagnosis. CASE REPORTS: Two patients demonstrating rapid cognitive decline as the primary symptom for neurosyphillis are described with particular focus on the diagnostic process complexity and adequate treatment delivery. CONCLUSIONS: Clinical manifestations as well as psychiatric symptoms of syphilis are diverse and often non-specific. The symptomatology of mood disorders in neurosyphilis is frequently atypical, intermittent, and pleomorphic and fails to meet DSM-5 diagnostic categories. Neurocognitive decline although could be one of the key symptoms domains in neurosyphilis. Those two cases emphasise the importance of specific differential diagnosis with rapid onset cognitive decline with spotlight to sexually transmitted diseases as syphilis.


Assuntos
Disfunção Cognitiva , Neurossífilis , Disfunção Cognitiva/etiologia , Humanos , Neurossífilis/complicações , Neurossífilis/diagnóstico , Treponema pallidum
17.
Psychiatr Danub ; 29(Suppl 3): 345-348, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953788

RESUMO

Antipsychotics are a key intervention strategy in pharmacotherapy of schizophrenia. However, benzodiazepines are often prescribed to control sleep disturbances, anxiety or behavioural disinhibition. There is clinical evidence for the beneficial effect of the combined treatment of antipsychotics and benzodiazepines resulting in more favorable treatment outcome in schizophrenia with regard to positive and negative symptoms. This clinical phenomenon seems to be associated with the GABA-ergic activit ythat is believed to be disrupted in the schizophrenia and direct benzodiazepines effect on GABA-A receptors. In the brain there are both excitatory and inhibitory neurotransmitters which cooperate between themselves maintaining the proper functioning of the brain. GABA neurons carry inhibitory signals that help keep brain activity at optimal levels of operation, Glutamate, on the other hand, carry excitatory signals. As the interplay between these two exists they keep the dopamine levels in the average levels. The disruption of GABA-ergic transmission in schizophrenia may induce alternations in dopaminergic neurotransmission providing no inhibitory effect to the central glutamate activity, resulting in the rise of the dopamine levels being associated with psychosis precipitation. Benzodiazepines are believed to reduce presynaptic dopamine release at the mesolimbic level and delay postsynaptic adaptation of dopaminergic neurons to antipsychotics potentiating the action of antipsychotics in resistant schizophrenia. Benzodiazepines also act on mesocortical regions where antipsychotics are less effective and where there is a particular sensitivity to stress. This association is particularly useful in resistant patients or in patients with severe anxiety with or without intolerance to antipsychotics. Improvement concerns anxious symptoms but also positive symptoms (hallucinations, delirium and dissociative syndrome) and negative (social withdrawal, affect flattening). As the available studies are limited there is some clinical evidence that the use of antipsychotic drugs with addition of benzodiazepines can provide better general outcome in ill patients than antipsychotics administration alone.


Assuntos
Antipsicóticos , Benzodiazepinas , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Humanos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Ácido gama-Aminobutírico
18.
Psychiatr Danub ; 29(Suppl 3): 349-352, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953789

RESUMO

Antipsychotics are a key intervention strategy in pharmacotherapy in schizophrenia. However, the benzodiazepines are often prescribed to control sleep disturbances, anxiety or hostile behaviour. There is some evidence supporting the combination therapy with antipsychotics and benzodiazepines providing beneficiary treatment effect to the psychosis in positive and negative symptom domains as well as catatonia or adverse reactions to antipsychotic drugs. In particular, in a population suffering from residual symptoms of schizophrenia, in particular anxiety, emotional flattening, being refractory to approved treatment strategies, benzodiazepines as add-on to antipsychotics seem to be an option. There is rationale for the therapeutic use for long-acting benzodiazepines as the treatment of option with limited literature indicating the use of chlordiazepoxide, and diazepam. The paper reviews the best clinical practice indications for benzodiazepines as the add-on treatment to antipsychotics in schizophrenia.


Assuntos
Antipsicóticos , Benzodiazepinas , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Terapia Combinada , Humanos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico
19.
Psychiatr Danub ; 29(Suppl 3): 357-360, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953791

RESUMO

BACKGROUND: There is evidence for neurosyphilis being associated with the central nervous system vasculitis involving medium and small vessels. As the hemispheric white matter is the major target of these vascular alterations the white matter axonal and myelination disruption may be observed employing measure for the rate of water molecule diffusion. High apparent diffusion coefficient (ADC) correspond to unimpeded water diffusion and indicating white matter disintegration. CASE REPORTS: In a retrospective study exploringcentral nervous system magnetic resonance (MR) images of two subjects presenting with neurosyphilis the ADC values were found to be increased as related to normal values being accompanied with normal appearing white matter of hemispheres. CONCLUSIONS: Applying ADC analysis to evaluate the brain in patients with neurosyphilis may reveal undetectable changes and explain the scale of abnormalities that occur in CNS. The increased mean ADC valuesin the normal appearing white matter of the hemispheres may correlate with neuropsychoatric symptomatology in syphilis.


Assuntos
Neurossífilis , Substância Branca , Imagem de Difusão por Ressonância Magnética , Humanos , Neurossífilis/complicações , Neurossífilis/diagnóstico por imagem , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
20.
Psychiatr Danub ; 29(Suppl 3): 361-364, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953792

RESUMO

BACKGROUND: Lithium carbonate is valuable and effective agent in the treatment and prophylaxis of mood disorders, particularly bipolar disorder (BD). Due to its narrow therapeutic range, frequent serum lithium estimation is necessary. To avoid the discomfort of frequent venipuncture, a non-invasive method for serum lithium concentration is needed. An alternative method of determining lithium level could be saliva or urine. Literature data regarding the reliability of saliva lithium levels is not conclusive. MATERIAL AND METHODS: The aim of this study is to provide an overview of possibility to replace blood serum with saliva look through research in that field. RESULTS: Some authors conclude that there is constant ratio between serum and saliva lithium level and they suggest that saliva can replace serum for estimation lithium level. Other revealed that saliva/serum lithium ratio is constant individually, so saliva/serum lithium ratio should be estimated individually. Finally there are studies excluding the possibility of replacement serum with saliva. CONCLUSIONS: There is little number of studies on saliva clinical use in lithium level monitoring. Further studies should base on current data including methods of obtaining saliva and its biochemical analysis, collecting samples in a specific time frame from the last dosage of lithium, as well as inter-subject or intra-subject measurements.


Assuntos
Antimaníacos , Transtorno Bipolar , Carbonato de Lítio , Antimaníacos/farmacocinética , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Humanos , Carbonato de Lítio/farmacocinética , Carbonato de Lítio/uso terapêutico , Reprodutibilidade dos Testes , Saliva/química
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