Doses repetidas de escetamina subcutânea para o tratamento de depressão refratária: resposta ao tratamento e impacto na cognição
Data
2023-09-15
Autores
Lucchese, Ana Cecilia 
Orientadores
Baxter, Sergio Andreoli
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Estudos indicam que doses subanestésicas de escetamina induzem a um efeito antidepressivo rápido. Há poucos dados sobre a via subcutânea (SC) de administração. Ainda não está claro para que perfil de pacientes esse tratamento seria adequado e o impacto deste sobre a cognição.
Objetivos: Examinar o efeito de doses subanestésicas repetidas de escetamina SC sobre sintomas depressivos, preditores clínicos de resposta e o impacto na cognição de pacientes com depressão refratária ao tratamento (unipolar e bipolar), considerados refratários pelo Método de Estadiamento de Maudsley (MSM). Métodos: Análise retrospectiva de 70 pacientes, que receberam seis doses de escetamina SC como tratamento adjuvante. O desfecho primário foi a redução dos sintomas depressivos. Análise de regressão logística investigou preditores clínicos de eficácia usando a redução de 50% (ou mais) nos escores da escala de Depressão de Montgomery-Asberg (MADRS) como variável dependente. Comparação entre os grupos e efeitos do tratamento foram examinadas pela análise de variância. Os desfechos secundários foram investigar o perfil cognitivo desta população, a segurança e o impacto do tratamento na cognição, estes foram analisados através do teste de qui-quadrado, teste t pareado e teste t para amostras independentes. A magnitude de efeito foi analisada pelo d de Cohen. Resultados: Nossa amostra apresentou grau de refratariedade grave ao tratamento em 65,7% (avaliado pelo MSM) e 47,1% tinham comorbidade com transtorno de ansiedade. A taxa de resposta foi de 50%. Tiveram melhor resposta os pacientes com escores de MSM leves e moderados (OR=3,162, p=0,041) e com comorbidade com transtorno de ansiedade (OR=3,149, p=0,028). Não foram observadas mudanças relevantes na cognição. Conclusões: Nossos resultados sugerem que altos níveis de refratariedade ao tratamento podem estar associados a pior resposta à escetamina SC. Pacientes com ansiedade comórbida, que costumam ter pior prognóstico no tratamento com farmacoterapias tradicionais, podem se beneficiar desta medicação. O tratamento se mostrou seguro em relação a cognição neste seguimento de curto prazo. Novas pesquisas são necessárias para confirmar estes resultados e estimular o maior destaque da escetamina no algoritmo de tratamento para depressão refratária.
Background: A large number of studies indicate that subanesthetic doses of esketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route. It remains unclear for whom this treatment is most suitable and its impact on cognition. Aims: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine, clinical predictors of response and impact on cognition in unipolar and bipolar treatment-resistant depression, as measured by the Maudsley Staging Method (MSM). Methods: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups and treatment effects were examined through analysis of variance. Secondary outcomes were investigating cognitive profile, treatment’s safety and impact on cognition, which were analyzed using chi-square test, paired t-test and t-test for independent samples. The magnitude of effect was analyzed using Cohen's d. Results: At baseline, our sample presented with severe treatment resistance in 65.7% (as assessed by MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR=3.162, p=0.041) and anxiety disorder comorbidity (OR=3.149, p=0.028). Significant changes in cognition were not observed. Conclusions: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with comorbid anxiety. Treatment proved to be safe regarding to cognition in a short follow up. Therefore, future research could investigate whether esketamine should receive a more prominent place in the algorithm for treatment-resistant depression.
Background: A large number of studies indicate that subanesthetic doses of esketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route. It remains unclear for whom this treatment is most suitable and its impact on cognition. Aims: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine, clinical predictors of response and impact on cognition in unipolar and bipolar treatment-resistant depression, as measured by the Maudsley Staging Method (MSM). Methods: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups and treatment effects were examined through analysis of variance. Secondary outcomes were investigating cognitive profile, treatment’s safety and impact on cognition, which were analyzed using chi-square test, paired t-test and t-test for independent samples. The magnitude of effect was analyzed using Cohen's d. Results: At baseline, our sample presented with severe treatment resistance in 65.7% (as assessed by MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR=3.162, p=0.041) and anxiety disorder comorbidity (OR=3.149, p=0.028). Significant changes in cognition were not observed. Conclusions: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with comorbid anxiety. Treatment proved to be safe regarding to cognition in a short follow up. Therefore, future research could investigate whether esketamine should receive a more prominent place in the algorithm for treatment-resistant depression.
Descrição
Citação
LUCCHESE, Ana Cecilia. Doses repetidas de escetamina subcutânea para o tratamento de depressão refratária: resposta ao tratamento e impacto na cognição. 2023. 63 f. Tese (Doutorado em Psiquiatria e Psicologia Médica) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2023.