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Escetamina no Tratamento da Depressão Resistente
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Abstract(s)
A depressão major é uma das perturbações psiquiátricas mais prevalentes a nível mundial, sendo responsável por uma carga significativa de morbilidade e incapacidade. Embora existam diversas opções farmacológicas eficazes, estima-se que cerca de 30% dos pacientes não apresentem resposta satisfatória a, pelo menos, dois tratamentos antidepressivos, em dose e duração adequadas. Nestes casos, considera-se a existência de uma depressão resistente ao tratamento, condição que representa um dos maiores desafios da psiquiatria moderna, quer pela complexidade dos seus mecanismos subjacentes, quer pela limitação das opções terapêuticas tradicionais. Face a esta problemática, têm vindo a ser estudadas novas abordagens farmacológicas, que permitam ultrapassar a resistência ao tratamento. Entre estas, destaca-se a escetamina, o S-enantiómero da quetamina, que atua como antagonista dos recetores NMDA e estimula, indiretamente, os recetores AMPA, promovendo um aumento da libertação de glutamato e a consequente neuroplasticidade sináptica, fatores considerados cruciais para a sua ação antidepressiva rápida e eficaz. O seu uso em contexto clínico foi aprovado em vários países, incluindo em Portugal, sob a forma de spray nasal, sendo geralmente administrada em combinação com um antidepressivo oral da classe dos inibidores seletivos da recaptação da serotonina ou dos inibidores da recaptação da serotonina e noradrenalina. Este trabalho tem como objetivo analisar a evidência disponível na área da Depressão Resistente ao Tratamento e as opções terapêuticas atuais, destacando a eficácia terapêutica da escetamina em doentes com depressão resistente ao tratamento, os principais efeitos adversos e as limitações à sua utilização, através da análise de estudos clínicos recentes. Foram também considerados os aspetos práticos associados à sua administração e a tolerabilidade ao tratamento.
Major depression is one of the most prevalent psychiatric disorders worldwide and is responsible for a significant burden of morbidity and disability. Although there are several effective pharmacological options, it is estimated that around 30% of patients do not show a satisfactory response to at least two antidepressant treatments, at an appropriate dose and duration. In these cases, treatment-resistant depression is considered to exist, a condition that represents one of the greatest challenges facing modern psychiatry, both because of the complexity of its underlying mechanisms and because of the limitations of traditional therapeutic options. In view of this problem, new pharmacological approaches have been studied to overcome resistance to treatment. These include esketamine, the S-enantiomer of ketamine, which acts as an antagonist of NMDA receptors and indirectly stimulates AMPA receptors, promoting an increase in glutamate release and consequent synaptic neuroplasticity, factors considered crucial for its rapid and effective antidepressant action. Its use in clinical settings has been approved in several countries, including Portugal, in the form of a nasal spray, usually administered in combination with an oral antidepressant from the class of selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors. The aim of this paper is to analyze the available evidence in the field of TreatmentResistant Depression and the current therapeutic options, highlighting the therapeutic efficacy of esketamine in patients with treatment-resistant depression, the main adverse effects and the limitations to its use, through the analysis of recent clinical studies. The practical aspects associated with its administration and treatment tolerability were also considered.
Major depression is one of the most prevalent psychiatric disorders worldwide and is responsible for a significant burden of morbidity and disability. Although there are several effective pharmacological options, it is estimated that around 30% of patients do not show a satisfactory response to at least two antidepressant treatments, at an appropriate dose and duration. In these cases, treatment-resistant depression is considered to exist, a condition that represents one of the greatest challenges facing modern psychiatry, both because of the complexity of its underlying mechanisms and because of the limitations of traditional therapeutic options. In view of this problem, new pharmacological approaches have been studied to overcome resistance to treatment. These include esketamine, the S-enantiomer of ketamine, which acts as an antagonist of NMDA receptors and indirectly stimulates AMPA receptors, promoting an increase in glutamate release and consequent synaptic neuroplasticity, factors considered crucial for its rapid and effective antidepressant action. Its use in clinical settings has been approved in several countries, including Portugal, in the form of a nasal spray, usually administered in combination with an oral antidepressant from the class of selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors. The aim of this paper is to analyze the available evidence in the field of TreatmentResistant Depression and the current therapeutic options, highlighting the therapeutic efficacy of esketamine in patients with treatment-resistant depression, the main adverse effects and the limitations to its use, through the analysis of recent clinical studies. The practical aspects associated with its administration and treatment tolerability were also considered.
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Keywords
Escetamina Depressão Resistente ao Tratamento Intranasal Antagonistas NMDA Psiquatria Esketamine Treatment-Resistant Depression NMDA Antagonists Psychiatry